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Nystagmus, hereditary vertical

Retrieved: 27-07-2015
Source: OMIM (Original article)

Description

Marmor (1973) reported 3 families in 2 of which the mother and 1 or more children were affected. Forsythe (1955) and Dichgans and Kornhuber (1964) described families in which male-to-male transmission was observed. Vertical nystagmus most often signifies acquired disease. The familial disorder is a motor-type vertical (and horizontal) nystagmus with associated mild ataxia. Most of the affected persons had absent optokinetic nystagmus and a hyperactive vestibuloocular response.

Symptoms

Eyes: Vertical nystagmus; Absent optokinetic nystagmus; Hyperactive vestibuloocular response

Neuro: Mild ataxia

Inheritance: Autosomal dominant

Hypotonia, congenital nystagmus, ataxia, and abnormal auditory brainstem responses

Retrieved: 27-07-2015
Source: OMIM (Original article)

Description

Polizzi et al. (1999) described a 5-year-old Italian boy with hypotonia, congenital nystagmus, ataxia, and abnormal auditory brainstem responses. The authors stated that this was the first Caucasian patient reported with this disorder, which had previously been described in 10 male Oriental patients, 2 of whom were sibs (Wang et al., 1989). Body weight was below the 3rd centile in many of the patients reported.
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Ataxia-microcephaly-cataract syndrome

Retrieved: 27-07-2015
Source: OMIM (Original article)

Description

In a highly inbred Arab family with ataxia-telangiectasia of complementation group A (ATA; 208900), Ziv et al. (1992) found 3 individuals who had ataxia, hypotonia, microcephaly, and congenital cataracts with nystagmus. Mental retardation was also observed in 1 of the 3 persons. The one individual appeared to be affected with both ataxia-telangiectasia and the AMC syndrome. Findings of the AMC syndrome resembled the Marinesco-Sjogren syndrome (MSS; 248800); however, microcephaly is not part of MSS, and mental retardation was present in only 1 of the AMC patients. Cataract is not characteristic of any of the known disorders that simulate ataxia-telangiectasia. That the AMC syndrome was an entity separate from AT in the Arab family was indicated by linkage studies.

Symptoms

Neuro: Ataxia; Hypotonia; Mental retardation

HEENT: Microcephaly; Congenital cataracts; Nystagmus

Inheritance: Autosomal recessive

Spinocerebellar ataxia type 16

Retrieved: 27-07-2015
Source: Orphanet (Original article)
Associated genes: itpr1

This disease has been moved to Spinocerebellar ataxia type 15/16

Spinocerebellar ataxia 15

Retrieved: 27-07-2015
Source: GARD (Original article)
Associated genes: itpr1

Spinocerebellar ataxia 15

Spinocerebellar ataxia 15 (SCA15) is a neurological condition characterized by slowly progressive gait and limb ataxia, often in combination with eye movement abnormalities and  balance, speech and swallowing difficulties. The onset of symptoms typically occurs between ages 7 and 66 years. The ability to walk independently is often maintained for many years following onset of symptoms. SCA15 is caused by mutations in the ITPR1 gene. It is inherited in an autosomal dominant manner. Diagnosis is based on clinical history, physical examination, molecular genetic testing, and exclusion of other similar diseases. There is no effective treatment known to modify disease progression. Patients may benefit from occupational and physical therapy for gait dysfunction and speech therapy for dysarthria

Spinocerebellar ataxia type 15/16

Retrieved: 27-07-2015
Source: Orphanet (Original article)
Associated genes: itpr1

Spinocerebellar ataxia type 15/16 (SCA15/16) is a rare subtype of type I autosomal dominant cerebellar ataxia (ADCA type I; see this term). It is characterized by cerebellar ataxia, tremor and cognitive impairment. Prevalence is unknown. Fewer than 80 patients affected by the disease have been identified to date. Age of onset is from 20 to 66 years (mean age = 39.6 years). Genetic testing has shown that patients originally classified under SCA15 and SCA16 have the same subtype caused by a deletion in the inositol 1,4,5-triphosphate receptor 1 ITPR1 gene (3p26.1). Prognosis is generally good and life-shortening events do not usually occur. Some patients live beyond 80 years of age. Expert reviewer(s) Dr Shinsuke FUJIOKA Dr Nathaniel WHALEY Dr Zbigniew WSZOLEK Last update: May 2011
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Brachydactyly - nystagmus - cerebellar ataxia

Retrieved: 27-07-2015
Source: Orphanet (Original article)

This syndrome is characterized by of brachydactyly, nystagmus and cerebellar ataxia It has been described in four generations of a family. Intellectual deficit and strabismus are also reported in some patients. Last update: June 2007
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Brachydactyly-nystagmus-cerebellar ataxia

Retrieved: 27-07-2015
Source: OMIM (Original article)

Description

Biemond (1934) described a syndrome consisting of brachydactyly (due to one short metacarpal and metatarsal), nystagmus and cerebellar ataxia in 4 generations of a family. Mental deficiency and strabismus were also present. Only a few members of the family had the full syndrome. Additional families are needed before this combination can be considered a single gene syndrome.

Symptoms

Limbs: Brachydactyly (one short metacarpal and metatarsal)

Eyes: Nystagmus; Strabismus

Neuro: Cerebellar ataxia; Mental deficiency

Inheritance: ? Autosomal dominant
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Episodic ataxia type 4

Retrieved: 27-07-2015
Source: Orphanet (Original article)

Episodic ataxia type 4 (EA4) is a very rare form of Hereditary episodic ataxia (see this term) characterized by late-onset episodic ataxia, recurrent attacks of vertigo, and diplopia. Last update: January 2014
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Episodic ataxia, type 4

Retrieved: 27-07-2015
Source: OMIM (Original article)

Clinical features

For a phenotypic description and a discussion of genetic heterogeneity of episodic ataxia, see EA1 (160120).In 16 members of a white, rural North Carolina family, Farmer and Mustian (1963) described recurrent attacks of vertigo, diplopia, and ataxia beginning in early adulthood. Slowly progressive cerebellar ataxia occurred in some. Vance et al. (1984) identified a second extensively affected kindred which, like the family of Farmer and Mustian (1963), lived in North Carolina. Although no relationship between the 2 kindreds could be established, such was suspected. Small et al. (1996) examined ocular motility in these families.

Damji et al. (1996) isolated DNA from 19 affected individuals from the 2 multigenerational North Carolina families originally described by Farmer and Mustian (1963) and Vance et al. (1984) who had periodic vestibulocerebellar ataxia in an autosomal dominant pedigree pattern. The disorder was characterized by defective smooth pursuit, gaze-evoked nystagmus, ataxia, and vertigo. The age of onset ranged from the third to the sixth decade.

Mapping

In the families originally described by Farmer and Mustian (1963) and Vance et al. (1984), Damji et al. (1996) excluded linkage to loci linked to EA1 and EA2 (108500), as well as to spinocerebellar ataxia types 1 (164400), 2 (183090), 3 (109150), 4 (600223), and 5 (600224).

Nomenclature

Damji et al. (1996) symbolized the disorder PATX for periodic ataxia.

Although Steckley et al. (2001) referred to PATX as episodic ataxia-3 (EA3) and the disorder in 606554 as EA4, the same group (Cader et al., 2005) later referred to the disorder described by Steckley et al. (2001) in 606554 as EA3. We have thus chosen to designate PATX as episodic ataxia-4 (EA4).

Symptoms

INHERITANCE: Autosomal dominant

HEAD AND NECK: [Ears]; Tinnitus; [Eyes]; Diplopia; Oscillopsia; Abnormal smooth pursuits; Inability to suppress vestibuloocular reflex (VOR); Gaze-evoked nystagmus; Esophoria

ABDOMEN: [Gastrointestinal]; Nausea

NEUROLOGIC: [Central nervous system]; Ataxia, episodic; Vertigo; Spasticity

MISCELLANEOUS: Age of onset 30 to 60 years; Symptoms precipitated by sudden movement, stress, exertion, fatigue' Attacks typically last for hours; Attacks are not responsive to acetazolamide
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Spinocerebellar ataxia autosomal recessive 7

Retrieved: 27-07-2015
Source: GARD (Original article)
Associated genes: tpp1

Spinocerebellar ataxia autosomal recessive 7

Spinocerebellar ataxia autosomal recessive 7, also called SCAR7, is a slowly progressive hereditary form of spinocerebellar ataxia.  Symptoms of SCAR7 can include difficulty walking and writing, speech difficulties (dysarthria), limb ataxia, and a decrease in the size of a region of the brain called the cerebellum (cerebellar atrophy). Of the few reported cases in the literature, some patients also had eye involvement that included nystagmus (in voluntary eye movements) and saccadic pursuit eye movements.  Out of 5 affected siblings examined in a large Dutch family, 2 became wheelchair-dependent late in life. The severity of the symptoms varies from mild to severe.  SCAR7 is caused by mutations in the TPP1 gene and is inherited in an autosomal recessive manner
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Spinocerebellar ataxia, autosomal recessive 7

Retrieved: 27-07-2015
Source: OMIM (Original article)
Associated genes: tpp1

Clinical features

A number sign (#) is used with this entry because autosomal recessive spinocerebellar ataxia-7 (SCAR7) is caused by compound heterozygous mutation in the TPP1 gene (607998) on chromosome 11p15.Breedveld et al. (2004) reported a Dutch family in which 5 sibs were affected with childhood-onset, slowly progressive spinocerebellar ataxia. The authors assumed autosomal recessive inheritance. All patients were examined as adults (age range from 46 to 64 years). Common clinical features included difficulty walking and writing, dysarthria, limb ataxia, and cerebellar atrophy. Three patients had nystagmus, 4 had saccadic pursuit eye movements, 2 had postural tremor, 4 had hyperreflexia, and 2 had extensor plantar responses. Three patients had decreased vibration sense, suggesting posterior column involvement. Two patients became wheelchair-dependent late in life. The severity of symptoms varied from mild to severe. Loci for common causes of autosomal dominant and autosomal recessive cerebellar ataxia were excluded.

Sun et al. (2013) reported a 51-year-old Dutch woman with SCAR7 confirmed by genetic analysis. She had onset of diplopia at the age of 18 years. She developed gait abnormalities 2 years later and was diagnosed with cerebellar atrophy at age 28. The disorder was slowly progressive, and she could still walk independently in middle age. Other features included loss of dexterity, dysarthria, swallowing difficulties, urinary urgency, and hyperreflexia. Brain MRI showed diffuse cerebellar atrophy, and laboratory studies showed decreased TPP1 activity. There was no family history of a similar disorder.

Inheritance

The transmission pattern in the family with SCAR7 reported by Breedveld et al. (2004) was consistent with autosomal recessive inheritance.

Mapping

By genomewide linkage analysis of a Dutch family with autosomal recessive spinocerebellar ataxia, Breedveld et al. (2004) identified a 5.9-cM candidate disease locus on chromosome 11p15 between markers D11S4088 and D11S1331 (maximum lod score of 3.3 at D11S1871).

Molecular genetics

In affected members of a Dutch family with autosomal recessive spinocerebellar ataxia-7, originally reported by Breedveld et al. (2004), Sun et al. (2013) identified compound heterozygous mutations in the TPP1 gene: a splice site mutati...

Symptoms

INHERITANCE: Autosomal recessive

HEAD AND NECK: [Eyes]; Nystagmus; Saccadic pursuit movements; Hypermetric saccades; Diplopia

NEUROLOGIC: [Central nervous system]; Cerebellar ataxia; Clumsiness in childhood; Gait ataxia; Limb ataxia; Postural tremor; Nystagmus; Dysarthria; Writing difficulties; Hyperreflexia; Extensor plantar responses; Decreased vibration sense, suggesting posterior column involvement; Cerebellar atrophy seen on MRI

MISCELLANEOUS: Onset in childhood or as young adult; Slow progression; Highly variable intrafamilial severity

MOLECULAR BASIS: Caused by mutation in the tripeptidyl peptidase 1 gene (TPP1, 607998.0004)
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Spinocerebellar ataxia, autosomal recessive 11

Retrieved: 27-07-2015
Source: OMIM (Original article)
Associated genes: syt14

Clinical features

A number sign (#) is used with this entry because this form of autosomal recessive spinocerebellar ataxia, referred to here as SCAR11, is caused by homozygous mutation in the SYT14 gene (610949) on chromosome 1q32.Doi et al. (2011) reported 2 Japanese brothers, born of consanguineous parents, with spinocerebellar ataxia associated with psychomotor retardation. One patient had mild psychomotor retardation since childhood, graduated from a normal junior high school, and held a job for several years, whereas the other had more severe psychomotor retardation, went to a school for the disabled, and later lived in an assisted facility. Both developed a progressive gait disorder in their fifties, followed by dysarthria, limb ataxia, truncal ataxia, and disturbance of smooth eye movements. One had nystagmus. Neither had involuntary movements. Brain MRI showed mild atrophy of the cerebellar vermis and hemispheres.

Inheritance

The transmission pattern in the family reported by Doi et al. (2011) was consistent with autosomal recessive inheritance.

Molecular genetics

By homozygosity mapping followed by whole-exome sequencing in 2 Japanese brothers with autosomal recessive SCA and mild to moderate psychomotor retardation, Doi et al. (2011) identified a homozygous mutation in the SYT14 gene (G484D; 610949.0001).

Symptoms

INHERITANCE: Autosomal recessive

HEAD AND NECK: [Eyes]; Impaired smooth pursuit; Nystagmus (1 patient)

ABDOMEN: [Gastrointestinal]; Dysphagia (1 patient)

NEUROLOGIC: [Central nervous system]; Psychomotor retardation, mild to moderate; Cerebellar ataxia; Limb ataxia; Truncal ataxia; Dysarthria; Cerebellar atrophy

MISCELLANEOUS: Onset of ataxia in the fifties; Slowly progressive; Two Japanese brothers have been reported (as of September 2011)

MOLECULAR BASIS: Caused by mutation in the synaptotagmin 14 gene (SYT14, 610949.0001)
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Spastic ataxia 7, autosomal dominant

Retrieved: 27-07-2015
Source: OMIM (Original article)

Clinical features

For a discussion of genetic heterogeneity of spastic ataxia, see SPAX1 (108600).Sanger Brown (1892) described a kindred with 21 persons in 4 generations who showed symmetric ataxia of gait and limb movement, dysarthria, and pyramidal signs in the limbs. Three had impaired pupillary reaction to light; at least 1 developed a disorder of conjugate eye movement. The proband had normal development until age 18 years, when he developed an ataxic gait associated with lower limb weakness and hyperreflexia. Upper limbs became involved later. He also reported dysarthria, dysphagia, and difficulties seeing at a distance. Physical examination as an adult showed significant ataxia, ankle clonus, hyperreflexia, and some abnormal movements suggestive of chorea. Ophthalmic examination showed ptosis, slow pupillary reaction, myopia, optic disc pallor, retinal atrophy, and color blindness. His 26-year-old sister developed ataxia in her twenties and also had poor visual acuity in the light. A brother of the 2 had similar features. In another branch of the family, 3 members had adult onset of progressive ataxia, dysarthria, and poor vision. Nystagmus was not present, but many had optic atrophy.

Dick et al. (1983) described a mother and 3 of her 5 children (2 males, 1 female) with hereditary spastic ataxia combined with congenital miosis. The affected persons were late in walking unaided and had slurred speech, small nonreacting pupils, and nystagmus. Deep tendon reflexes were increased and the plantar reflexes were often extensor.

Timby et al. (2008) reported a Swedish family in which 4 individuals spanning 3 generations had early childhood-onset spastic ataxia and pupillary miosis. Onset of independent walking occurred by age 2 or 3 years, but all showed truncal and gait ataxia. All also had miotic pupils that did not dilate in the dark. Most patients had balance problems and were unable to stand on 1 leg or with closed eyes. Other features included dysdiadochokinesis, hyperreflexia mainly affecting the legs, and mild dysarthria. The ataxia was present from the first years of life, but the miosis started between ages 4 and 16 years.

Inheritance

The transmission pattern of the disorder in the families reported by Brown (1892) and Dick et al. (1983) suggested autosomal dominant inheritance.

Symptoms

INHERITANCE: Autosomal dominant

HEAD AND NECK: [Eyes]; Miosis; Lack of pupillary dilation in the dark; Optic atrophy (in some patients); Nystagmus (in some patients)

NEUROLOGIC: [Central nervous system]; Delayed independent walking; Ataxia, gait; Ataxia, truncal; Dysarthria, mild; Dysdiadochokinesis; Hyperreflexia, lower limbs more than upper limbs

MISCELLANEOUS: Variable age at onset (range childhood to adult)
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Cerebellar ataxia, Cayman type

Retrieved: 27-07-2015
Source: Orphanet (Original article)
Associated genes: atcay

Cerebellar ataxia, Cayman type is characterised by psychomotor retardation, hypotonia and cerebellar dysfunction (nystagmus, ataxic gait, truncal ataxia, dysarthric speech and intention tremor), associated with cerebellar hypoplasia. The prevalence is unknown, but the disorder is very rare in the general population. However, a founder mutation has led to a high incidence in the Cayman island population. The disorder is transmitted as an autosomal recessive trait and is caused by mutations in the ATCAY gene (19p13.3), encoding Caytaxin. Last update: June 2007
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Familial paroxysmal ataxia

Retrieved: 27-07-2015
Source: Orphanet (Original article)

Episodic ataxia type 2 (EA2) is the most frequent form of Hereditary episodic ataxia (EA; see this term) characterized by paroxysmal episodes of ataxia lasting hours, with interictal nystagmus and mildly progressive ataxia. Last update: January 2014
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Episodic ataxia, type 2

Retrieved: 27-07-2015
Source: OMIM (Original article)

Description

A number sign (#) is used with this entry because episodic ataxia type 2 (EA2) is caused by mutation in the calcium ion channel gene CACNA1A (601011).Episodic ataxia is a genetically heterogeneous neurologic condition characterized by spells of incoordination and imbalance, often associated with progressive ataxia. Episodic ataxia type 2 is the most common form of EA (Jen et al., 2007).

For a discussion of genetic heterogeneity of episodic ataxia, see EA1 (160120).

Clinical features

Parker (1946) may have been the first to describe this disorder. Hill and Sherman (1968) described episodic cerebellar ataxia occurring particularly in children in a large kindred with an autosomal dominant pattern of inheritance. The symptoms ameliorated in later life with no permanent or progressive cerebellar abnormalities. The cases presented by White (1969) showed gradual abatement of symptoms.

Donat and Auger (1979) reported ataxia in a 16-year-old boy and his 41-year-old mother, both of whom had 'downbeating nystagmus' of the eyes when in the primary position of gaze. The attacks of dizziness, which began at the age of 9 in the boy, were relieved with acetazolamide. Koller and Bahamon-Dussan (1987) reported a family with affected individuals in 3 generations, including 1 instance of male-to-male transmission. Stress or emotion precipitated attacks. Examination between attacks showed nystagmus, but no other neurologic signs. After adolescence, there was no progression of symptoms. The authors found, as have others (e.g., Zasorin et al., 1983), that acetazo...

Symptoms

INHERITANCE: Autosomal dominant

HEAD AND NECK: [Ears]; Tinnitus; [Eyes]; Ictal and interictal diplopia; Suppression of vestibuloocular reflex; Saccadic smooth pursuit; Gaze-evoked nystagmus; Interictal downbeat nystagmus; Ocular abnormalities often persist between attacks

NEUROLOGIC: [Central nervous system]; Ataxia, episodic; Unsteadiness, episodic; Vertigo; Myotonia; Dysarthria; Migraine headache; Weakness; Paresthesias; Interictal downbeat nystagmus; Interictal vestibular dysfunction; Interictal dystonia may occur later in disease course; Interictal ataxia may occur later in disease course; EEG with paroxysmal activity; Atrophy of cerebellar vermis

MISCELLANEOUS: Most common episodic ataxia syndrome; Onset usually in childhood or adolescence; Onset may occur in adulthood; Incomplete penetrance; Progressive ataxia; Episodes last from several hours to days; Frequency of episodes ranges from several per week to several per year; Symptoms precipitated by sudden movement, stress, exertion, exercise, fatigue, caffeine, alcohol, cigarettes; Favorable response of episodic attacks to acetazolamide; Phenotypic overlap with FHM1 (141500) and SCA6 (183086)

MOLECULAR BASIS: Caused by mutation in the calcium channel, voltage-dependent, P/Q type, alpha 1A subunit gene (CACNA1A, 601011.0005)
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Autosomal recessive ataxia, Beauce type

Retrieved: 27-07-2015
Source: Orphanet (Original article)
Associated genes: syne1

This syndrome is characterised by a slowly progressive pure cerebellar ataxia associated with dysarthria. It has been described in 53 individuals from 26 families of Canadian origin. The mode of transmission is autosomal recessive. Positional cloning has led to the identification of several gene mutations. Last update: January 2007
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Spinocerebellar ataxia 13

Retrieved: 27-07-2015
Source: GARD (Original article)
Associated genes: kcnc3

Spinocerebellar ataxia 13

Spinocerebellar ataxia 13 (SCA13) is a rare sub-type of spinocerebellar ataxias, a group of neurological conditions characterized by degeneration of the brain and spinal cord. Signs and symptoms of SCA13 appear to vary among affected people and range from childhood-onset, slowly progressive gait ataxia and dysarthria (often with intellectual disability and occasional seizures) to adult-onset progressive ataxia. Life expectancy is normal. SCA13 is caused by mutations in the KCNC3 gene and is inherited in an autosomal dominant manner. Treatment may include anti-seizure medications; assistive devices (such as a canes and walkers); and/or speech therapy and communication devices
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Spinocerebellar ataxia type-13

Retrieved: 27-07-2015
Source: WIKIPEDIA (Original article)
Associated genes: kcnc3
Spinocerebellar ataxia type 13 (SCA13) is a rare autosomal dominant disorder, which, like other types of SCA, is characterized by dysarthria, nystagmus, and ataxia of gait, stance and the limbs due to cerebellar dysfunction. Patients with SCA13 also tend to present with epilepsy, an inability to run, and increased reflexes. This cerebellar dysfunction is permanent and progressive. SCA13 is caused by mutations in KCNC3, a gene encoding a voltage-gated potassium channel KV3.3. There are two known mutations in this gene causative for SCA13. Unlike many other types of SCA, these are not polyglutamine expansions but, rather, point mutations resulting in channels with no current or altered kinetics.

Signs and symptoms

SCA13 is typified by early onset, mildly progressive cerebellar ataxia with accompanying dysarthria, mental retardation, and nystagmus. Symptoms and age of onset can vary slightly according to the causative mutation.

Pathophysiology

Mutations in KCNC3 are responsible for SCA13. This gene is expressed heavily in Purkinje cells, as is the case for some other SCA subtypes, where it is believed to play an important role in facilitating high-frequency action potential firing. There are two known mutations in this gene associated with SCA13. The first mutation, R420H, is located in the voltage-sensing S4 segment of the channel. As this mutation neutralizes a site important for voltage sensing, it is not surprising that it results in non-conducting channels. Neurons expressing such channels are unable to follow high-frequency input with adequate fidelity. The second SCA13 associated mutation, F448L, results in functional channels that have altered kinetics. The voltage for half activation of these channels (V½) is shifted 13mV hyperpolarized compared to wild-type. Deactivation of these channels is also slowed drastically compared to wild-type. This results in neurons with longer after-hyperpolarizations and thus, a decreased maximal firing rate.

Prognosis

There is no known prevention of spinocerebellar ataxia. Those who are believed to be at risk can have genetic sequencing of known SCA loci performed to confirm inheritance of the disorder.

External links

GeneReviews/NCBI/NIH/UW entry on Spinocerebellar Ataxia Type 13
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Spinocerebellar ataxia 13

Retrieved: 27-07-2015
Source: OMIM (Original article)
Associated genes: kcnc3

Clinical features

A number sign (#) is used with this entry because spinocerebellar ataxia-13 (SCA13) is caused by heterozygous mutation in the voltage-gated potassium channel, Shaw-related subfamily, member-3 gene (KCNC3; 176264).

For a general discussion of autosomal dominant spinocerebellar ataxia, see SCA1 (164400).Herman-Bert et al. (2000) described a large French family in which 8 members were affected with autosomal dominant spinocerebellar ataxia. There were 7 affected women and an affected 4-year-old boy. Clinical features included slowly progressive childhood-onset cerebellar gait ataxia associated with cerebellar dysarthria, moderate mental retardation (IQ, 62-76), and mild developmental delay in motor acquisition. Nystagmus and pyramidal signs were also observed in some patients. Cerebral magnetic resonance imaging in 2 patients showed moderate cerebellar and pontine atrophy.

Waters et al. (2005) reported a 3-generation Filipino family in which 11 members had autosomal dominant SCA. The 82-year-old proband was the oldest affected, with disease onset at age 60 years. Mean ages at onset in the second and third generations were 36.4 and 24.5 years, respectively. Clinical features included gait ataxia, limb ataxia/dysmetria, titubation, hypotonia, dysarthria, and nystagmus. Mental retardation was not a feature. Waters et al. (2005) noted that the phenotype in the Filipino family differed from that in the French family reported by Herman-Bert et al. (2000).

Mapping

By genomewide analysis of a French family with SCA, Herman-Bert et al. (2000) found significant evidence for linkage to an 8-cM interval on chromosome 19q13.3-q13.4 between markers D19S219 and D19S553. The locus was termed SCA13.

In a Filipino family with SCA, Waters et al. (2005) found linkage to a 4-cM region on 19q13 (lod score of 3.89) that overlapped with the SCA13 locus reported by Herman-Bert et al. (2000).

Molecular genetics

In affected members of a French family and a Filipino family with SCA13, Waters et al. (2006) identified 2 different heterozygous mutations in the KCNC3 gene (176264.0001; 176264.0002).

Symptoms

INHERITANCE: Autosomal dominant

HEAD AND NECK: [Eyes]; Nystagmus

NEUROLOGIC: [Central nervous system]; Progressive cerebellar ataxia; Gait ataxia; Limb ataxia; Limb dysmetria; Hypotonia; Delayed motor development; Inability to run; Dysarthria; Hyperreflexia; Mental retardation (reported in 1 family); Pyramidal signs; Cerebellar atrophy

MISCELLANEOUS: Variable age at onset, ranging from childhood to late adulthood; Slow disease progression

MOLECULAR BASIS: Caused by mutation in the voltage-gated potassium channel, Shaw-related subfamily, member 3 gene (KCNC3, 176264.0001)
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Episodic ataxia, type 5

Retrieved: 27-07-2015
Source: OMIM (Original article)
Associated genes: cacnb4

Clinical features

A number sign (#) is used with this entry because of evidence that episodic ataxia-5 is caused by heterozygous mutation in the CACNB4 gene (601949) on chromosome 2q22-q23.

For a general description and a discussion of genetic heterogeneity of episodic ataxia, see EA1 (160120).Escayg et al. (2000) reported a French Canadian family segregating episodic ataxia. The proband, after age 20 years, experienced recurrent episodes of vertigo and ataxia that lasted for several hours. Interictal examination showed spontaneous downbeat and gaze-evoked nystagmus and mild dysarthria and truncal ataxia. The proband's mother had identical episodes of vertigo and ataxia after age 30 years as well as longstanding dysarthria and imbalance. Acetazolamide prevented the attacks in both the proband and the mother, and the attacks recurred when acetazolamide was briefly discontinued.

Molecular genetics

In affected members of a French Canadian family segregating episodic ataxia, Escayg et al. (2000) identified heterozygosity for a missense mutation in the CACNB4 gene (601949.0002). Herrmann et al. (2005) referred to the form of ataxia caused by mutation in the CACNB4 gene as episodic ataxia type 5.
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Spinocerebellar ataxia type 31

Retrieved: 27-07-2015
Source: Orphanet (Original article)
Associated genes: bean1, plekhg4

Spinocerebellar ataxia type 31 (SCA31) is a very rare subtype of autosomal dominant cerebellar ataxia type 3 (ADCA type 3; see this term) characterized by the late-onset of cerebral ataxia, dysarthria, and horizontal gaze nystagmus, and that is occasionally accompanied by pyramidal signs, tremor, decreased vibration sense, and hearing difficulties. SCA31 is the third most common form of ADCA (see this term) in Japan, where more than 20 families have been reported to date. It is rarely found in other Asian countries and is extremely rare in Western countries. The mean age of disease onset is 58 years but it can present between the ages of 8 to 83 years. Ataxia, dysarthria, and horizontal gaze nystagmus are the common manifestations of SCA31 and the disease duration can be more than 10 years. Less common manifestations include pyramidal signs, tremor, decreased vibration sense, and hearing difficulties. SCA31 is due to non-coding pentanucleotide repeat expansions in the brain expressed, associated with NEDD4, 1 (BEAN1) gene (16q21). SCA31 is inherited autosomal dominantly with incomplete penetrance and genetic counseling is possible. Expert reviewer(s) Dr Shinsuke FUJIOKA Dr Zbigniew WSZOLEK Dr Shozaburo YANAMOTO Last update: November 2014
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Cerebellar hypoplasia

Retrieved: 27-07-2015
Source: OMIM (Original article)

Description

Crouzon (1929) and Sarrouy et al. (1957) reported 2 pairs of sibs with congenital cerebellar hypoplasia. Norman and Urich (1958) noted parental consanguinity in an isolated case. Wichman et al. (1985) reported 3 pairs of affected sibs in unrelated families. All 6 presented within the first 6 months of life with delayed motor and language development. Mathews et al. (1989) also described autosomal recessive cerebellar hypoplasia. Dooley et al. (1992) reported 2 sisters with cerebellar hypoplasia who also had nonprogressive retinal pigmentary disease. They pointed out that 1 of the 2 sibs reported by Mathews et al. (1989) had bilateral retinal pigmentary changes.

It is not certain that the disorder designated cerebellar hypoplasia is distinct from the Norman type of nonprogressive autosomal recessive cerebellar ataxia (213200).

Symptoms

Neuro: Ataxia; Hypotonia; Ataxia; Tremor; Cerebellar hypoplasia

Eyes: Nystagmus

Inheritance: Autosomal recessive
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Spinocerebellar ataxia type 30

Retrieved: 27-07-2015
Source: Orphanet (Original article)
Associated genes: cyp11b2, sca30

Spinocerebellar ataxia type 30 (SCA30) is a very rare subtype of autosomal dominant cerebellar ataxia type 3 (ADCA type 3; see this term) characterized by a slowly progressive and relatively pure ataxia. SCA30 has only been described in 6 patients from one Australian family to date. The age of onset ranges from 45 to 76 years with a mean age of onset of 52 years. It presents with oculomotor dysfunction, moderate dysarthria and ataxia that progresses slowly and eventually leads to mobility impairment. Some patients have also reported mild hyperreflexia in the lower limbs. Rarer manifestations include gaze-evoked nystagmus and dystonia. The causal gene has not yet been identified but it has been linked to chromosome 4q34.3-q35.1. SCA30 is inherited in an autosomal dominant manner and genetic counseling is possible. Expert reviewer(s) Dr Shinsuke FUJIOKA Dr Zbigniew WSZOLEK Dr Shozaburo YANAMOTO Last update: November 2014
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Spinocerebellar ataxia 30

Retrieved: 27-07-2015
Source: OMIM (Original article)
Associated genes: cyp11b2, sca30

Clinical features

For a general discussion of autosomal dominant spinocerebellar ataxia, see SCA1 (164400).Storey et al. (2009) reported an Australian family of Anglo-Celtic origin in which 6 individuals had a relatively pure, slowly evolving ataxia inherited in an autosomal dominant pattern. The mean reported age at onset was 52 years (range 45 to 76), but the onset was typically so insidious that it was difficult to establish. The phenotype was characterized by relatively pure, slowly evolving gait and appendicular ataxia with mild to moderate dysarthria. Four individuals had mild lower limb hyperreflexia; none had evidence of neuropathy. All patients had hypermetric saccades with normal vestibuloocular reflex gain. One patient had slight gaze-evoked nystagmus. Brain MRI of 2 patients showed cerebellar atrophy with preservation of the brainstem.

Mapping

By genomewide linkage analysis of an Australian family with a relatively pure form of spinocerebellar ataxia, Storey et al. (2009) identified a locus, termed SCA30, on chromosome 4q34.3-q35.1 (lod score of 3.0). Haplotype analysis delineated a 5-Mb region between dbSNP rs1397413 and dbSNP rs2175476. ODZ3 (610083) was identified as a plausible candidate gene.

Symptoms

INHERITANCE: Autosomal dominant

HEAD AND NECK: [Eyes]; Hypermetric saccades; Gaze-evoked nystagmus (1 patient)

NEUROLOGIC: [Central nervous system]; Ataxia, gait and appendicular; Dysarthria; Hyperreflexia, lower limbs, mild; Cerebellar atrophy

MISCELLANEOUS: Adult onset (45 to 76 years); Insidious onset; Slow progression; One family has been reported (as of 4/2010)
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Endosteal sclerosis - cerebellar hypoplasia

Retrieved: 27-07-2015
Source: Orphanet (Original article)

This syndrome is characterized by congenital cerebellar hypoplasia, endosteal sclerosis, hypotonia, ataxia, mild to moderate developmental delay, short stature, hip dislocation, and tooth eruption disturbances. It has been described in four patients. Less common manifestations are microcephaly, strabismus, nystagmus, optic atrophy, and dysarthria. It is appears to be transmitted as an autosomal recessive trait. Last update: June 2007
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Cerebellar hypoplasia with endosteal sclerosis

Retrieved: 27-07-2015
Source: OMIM (Original article)

Description

Cerebellar hypoplasia with endosteal sclerosis appears to have been described first by Stoll et al. (1986). The parents in this case were consanguineous.

Charrow et al. (1991) described a brother and sister and an unrelated boy with congenital cerebellar hypoplasia and endosteal sclerosis. All 3 children presented with ataxia and developmental delay and were found to have microcephaly, short stature, oligodontia, strabismus, nystagmus, and congenital hip dislocation.

Ozgen et al. (2005) described the disorder in a girl who they had followed for 11 years. The major clinical symptoms were cerebellar hypoplasia causing ataxia, hypotonia, mild to moderate developmental delay, growth retardation, endosteal sclerosis, tooth eruption disturbances, and hip dislocations. The endosteal sclerosis remained stationary over time, as did the clinical neurologic symptoms, but neuroradiologic manifestations slowly progressed. Ozgen et al. (2005) concluded that the disorder is probably autosomal recessive.

Symptoms

Neuro: Congenital cerebellar hypoplasia; Ataxia; Developmental delay

Cranium: Microcephaly

Growth: Short stature

Teeth: Oligodontia

Eyes: Strabismus; Nystagmus

Skel: Congenital hip dislocation; Endosteal sclerosis

Inheritance: Autosomal recessive
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Spinocerebellar ataxia 5

Retrieved: 27-07-2015
Source: GARD (Original article)

Spinocerebellar ataxia 5

Spinocerebellar ataxia 5 (SCA5) is one of the many spinocerebellar ataxias, which are inherited conditions that cause degeneration of the spinal cord and cerebellum. SCA5 almost exclusively affects the cerebellum. It is considered to be a mild form that progresses slowly. The age of onset is usually between the ages of 20 and 30, but a wide range in age of onset has been reported. Signs and symptoms may include loss of coordination of the hands, arms, and legs; impaired balance when walking; and slurred speech (dysarthria). SCA5 is caused by mutations in the SPTBN2 gene and is inherited in an autosomal dominant manner
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Spinocerebellar ataxia type 5

Retrieved: 27-07-2015
Source: Orphanet (Original article)

Spinocerebellar ataxia type 5 (SCA5) is a rare subtype of autosomal dominant cerebellar ataxia type 3 (ADCA type 3; see this term) characterized by the early-onset of cerebellar signs with eye movement abnormalities and a very slow disease progression. The prevalence is unknown. Three families (American, French and German) with SCA5 have been reported to date. The mean age of onset is 33 years but it can range from 10-68 years. SCA5 patients clinically present with cerebellar signs (ataxia, dysarthria, and intention tremor) with eye movement abnormalities such as gaze-evoked nystagmus, down beat nystagmus, and impaired smooth pursuit. Occasionally defects of the visual field and horizontal gaze palsy can be also present. Non-cerebellar signs such as facial myokimia, resting tremor, writer's cramp, impaired vibration sense and brisk deep tendon reflexes have been reported in some patients. SCA5 progresses very slowly with a disease duration of more than 30 years after symptom onset. SCA5 is caused by mutations in the SPTBN2 gene (11q13.2) encoding beta-III spectrin, a protein essential for the correct functioning and development of Purkinje cells. SCA5 is inherited autosomal dominantly and genetic counseling is possible. Expert reviewer(s) Dr Shinsuke FUJIOKA Dr Zbigniew WSZOLEK Dr Shozaburo YANAMOTO Last update: November 2014
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Acute cerebellar ataxia of childhood

Retrieved: 27-07-2015
Source: WIKIPEDIA (Original article)
Acute cerebellar ataxia of childhood is a childhood condition characterized by an unsteady gait, most likely secondary to an autoimmune of postinfectious cause, drug induced or paraneoplastic.Brown, Miller. "Pediatrics." Lipincott Williams and Wilkins, 2005, pp 380. Most common virus causing acute cerebellar ataxia are Chickenpox virus and Epstein Barr Virus. It is a diagnosis of exclusion

Epidemiology

Acute cerebellar ataxia is the most common cause of unsteady gait in children. The condition is rare in children older than ten years of age. Most commonly acute cerebellar ataxia affects children between age 18 mo and 7 years.

Etiology

Most common cause of acute cerebellar ataxia is varicella infection. Other viruses include influenza, Epstein-Barr virus, Coxsackie virus, Echo virus or mycoplasma. The possible mechanism is immune complex deposition in the cerebellum.

Clinical features

Acute cerebellar ataxia usually follows 2–3 weeks after an infection. Onset is abrupt. Vomiting may be present at the onset but fever and nuchal rigidity characterestically are absent. Horizontal nystagmus is present is approximately 50% of cases. Truncal ataxia with deterioration of gait Slurred speech and nystagmus Afebrile

Diagnosis

Acute Cerebellar ataxia is a diagnosis of exclusion. Urgent CT scan is necessary to rule out cerebellar tumor or hemorrhage as cause of the ataxia; however in acute cerebellar ataxia, the CT will be normal. CSF studies are normal earlier in the course of disease. Later on CSF shows moderate elevation of proteins.

Management

Supportive treatment is the only intervention for acute cerebellar ataxia of childhood. Symptoms may last as long as 2 or 3 months.

Differential Diagnosis

Brain tumors, including cerebellar astrocytoma, medulloblastoma, neuroblastoma Cerebellar contusion Subdural hematoma Toxins, including ethanol or anticonvulsants Cerebellar infarction or hemorrhage Meningitis Encephalitis Acute disseminated encephalomyelitis Multiple sclerosis

References

See Also http://www.nlm.nih.gov/medlineplus/ency/article/001397.htm
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VLDLR-associated cerebellar hypoplasia

Retrieved: 27-07-2015
Source: WIKIPEDIA (Original article)
VLDLR-associated cerebellar hypoplasia (VLDLRCH; alternative names: dysequilibrium syndrome, DES; nonprogressive cerebellar disorder with mental retardation) is a rare autosomal recessive condition caused by a disruption of the VLDLR gene. First described as a form of cerebral palsy in the 1970s,Sanner, G. The dysequilibrium syndrome: a genetic study. Neuropaediatrie 4: 403-413, 1973 it is associated with parental consanguinity and is found in secluded communities, with a number of cases described in Hutterite families.

External links

GeneReviews/NCBI/NIH/UW entry on VLDLR-associated cerebellar hypoplasia OMIM record
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Spinocerebellar ataxia type 27

Retrieved: 27-07-2015
Source: Orphanet (Original article)
Associated genes: fgf14

Spinocerebellar ataxia type 27 (SCA27) is a very rare subtype of type I autosomal dominant cerebellar ataxia (ADCA type I; see this term). It is characterized by early-onset tremor, dyskinesia, and slowly progressive cerebellar ataxia. Fewer than 30 cases have been reported to date. This subtype is caused by a mutation in the fibroblast growth factor 14 FGF14 gene (13q34). Prognosis is relatively good. Patients can walk unassisted until the 7th decade of life. Life-threatening status epilepticus and intractable seizure or severe dysphagia are rare. Expert reviewer(s) Dr Shinsuke FUJIOKA Dr Nathaniel WHALEY Dr Zbigniew WSZOLEK Last update: May 2011
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Spinocerebellar ataxia 27

Retrieved: 27-07-2015
Source: OMIM (Original article)
Associated genes: fgf14

Clinical features

A number sign (#) is used with this entry because spinocerebellar ataxia-27 (SCA27) is caused by mutation in the gene encoding fibroblast growth factor-14 (FGF14; 601515).

For a general discussion of autosomal dominant spinocerebellar ataxia, see SCA1 (164400).Van Swieten et al. (2003) reported a large 3-generation Dutch family in which 14 members had cerebellar ataxia inherited in an autosomal dominant pattern. Since childhood, all patients had trembling of both hands, which was exacerbated by emotional stress and physical exercise. Mild unsteadiness and ataxia of the upper limbs, especially under unusual circumstances, began at age 15 to 20 years. Six patients did not complete primary education, and only 4 of the 14 attended secondary school. Aggressive outbursts were mentioned in 5 patients and depression in 3. Neurologic examination showed dysmetric saccades, disrupted ocular pursuit movements, gaze-evoked nystagmus, cerebellar dysarthria, and a high-frequency, small-amplitude tremor in both hands in most of the patients. Six patients showed head tremor, and subtle orofacial dyskinesias were seen in 8. Severe limb and gait ataxia were present in the 3 eldest patients. Two patients showed cerebellar atrophy on MRI. The inability to complete primary education, low cognitive performances, and aggressive outbursts in several of the patients may reflect changes in the development and survival of neuronal populations in the cerebral cortex, amygdala, and basal ganglia.

Dalski et al. (2005) reported an ataxia patient with mild mental retardation (IQ of 70), inborn strabismus, and red-green colorblindness. His motor development was normal until age 12 years, when he developed a slowly progressive gait disturbance, memory loss, and depressed mood. Clinical examination at age 13 years showed truncal and gait ataxia, small-amplitude...

Symptoms

INHERITANCE: Autosomal dominant

HEAD AND NECK: [Face]; Orofacial dyskinesias; [Eyes]; Gaze-evoked nystagmus; Dysmetric saccades; Disrupted ocular pursuit movements; Strabismus; Red-blind color blindness (reported in 1 patient)

SKELETAL: [Feet]; Pes cavus

NEUROLOGIC: [Central nervous system]; Cerebellar ataxia; Gait ataxia; Limb ataxia; Truncal ataxia; Tremor, small-amplitude, high-frequency, restricted to the hands; Head tremor, mild; Tremor is exacerbated by stress and exercise; Gaze-evoked nystagmus; Dysarthria; Memory loss; Poor cognition; Mental retardation, mild; Cerebellar atrophy; Basal ganglia degeneration; [Peripheral nervous system]; Sensory axonal neuropathy, mild; [Behavioral/psychiatric manifestations]; Aggressive outbursts; Depression

MISCELLANEOUS: Onset in late-childhood to early adulthood (12 to 20 years); Slowly progressive; Genetic heterogeneity (see SCA1, 164000)

MOLECULAR BASIS: Caused by mutation in the fibroblast growth factor gene-14 (FGF14, 601515.0001)
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Spinocerebellar ataxia type 26

Retrieved: 27-07-2015
Source: Orphanet (Original article)
Associated genes: cacna1a, eef2, sca26

Spinocerebellar ataxia type 26 (SCA26) is a very rare subtype of autosomal dominant cerebellar ataxia type 3 (ADCA type 3; see this term) characterized by late-onset and slowly progressive cerebellar signs (gait ataxia) and eye movement abnormalities. To date, only 23 affected patients have been described from one American family of Norwegian descent. Disease onset occurs between the ages of 26-60 with a mean age of onset of 42 years. Slowly progressive gait ataxia, dysarthria, nystagmus, impaired pursuit, and dysmetric saccades were reported in all patients. Left-sided pyramidal signs (hyperreflexia with positive Babinski sign) were reported in one patient. The disease duration is unknown. A candidate gene for SCA26 has recently been identified as the eukaryotic translation elongation factor 2 (EEF2) gene, located on chromosome 19p13.3. Further confirmatory studies are still required in order to determine if a mutation in this gene directly causes SCA26. SCA26 is inherited autosomal dominantly and genetic counseling is possible. Expert reviewer(s) Dr Shinsuke FUJIOKA Dr Zbigniew WSZOLEK Dr Shozaburo YANAMOTO Last update: November 2014
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Spinocerebellar ataxia 26

Retrieved: 27-07-2015
Source: OMIM (Original article)
Associated genes: cacna1a, eef2, sca26

Clinical features

A number sign (#) is used with this entry because of evidence that spinocerebellar ataxia-26 (SCA26) is caused by heterozygous mutation in the EEF2 gene (130610) on chromosome 19p. One such family has been reported.

For a general discussion of autosomal dominant spinocerebellar ataxia, see SCA1 (164400).Yu et al. (2005) reported a 6-generation family with autosomal dominant pure spinocerebellar ataxia. The proband presented at age 40 years with a 13-year history of slowly progressive gait ataxia, upper limb ataxia, and dysarthria. Family history revealed that multiple other members were affected, and 15 members were examined. Age at onset ranged from 26 to 60 years (mean, 42 years). The disorder was characterized by pure cerebellar signs, including ataxia of the trunk and limbs, dysarthria, and irregular visual pursuit movements. Intelligence was normal. MRI showed atrophy of the cerebellum sparing the pons and medulla. Anticipation was not observed. The family was of Norwegian ancestry and had immigrated to North Dakota. Hekman et al. (2012) conducted neuropathologic examination of 2 affected individuals from the family reported by Yu et al. (2005). Both showed significant loss of Purkinje cells in the cerebellar vermis with minimal or no neuronal loss in other brain regions.

Inheritance

The transmission pattern in the family with SCA26 reported by Yu et al. (2005) was consistent with autosomal dominant inheritance.

Mapping

By genomewide linkage analysis of a large family with pure spinocerebellar ataxia, Yu et al. (2005) identified a 15.55-cM candidate disease locus, designated SCA26, on chromosome 19p13.3 between markers D19S886 and D19S894 (maximum lod score greater than 15). Yu et al. (2005) noted that SCA26 maps close to SCA6 (183086), but that CACNA1A (601011), the gene mutant in that disorder, is approximately 19 cM centromeric to SCA26. Moreover, genetic analysis showed that the proband carried CACNA1A wildtype alleles.

Molecular genetics

In affected members of a family of Norwegian origin with autosomal dominant late-onset spinocerebellar ataxia-26, previously reported by Yu et al. (2005), Hekman et al. (2012) identified a heterozygous mutation in the EEF2 gene (P596H; 130610.0001). Detailed studies of the equivalent mutation in y...

Symptoms

INHERITANCE: Autosomal dominant

HEAD AND NECK: [Eyes]; Nystagmus; Irregular visual pursuit movements

NEUROLOGIC: [Central nervous system]; Cerebellar ataxia; Gait ataxia; Limb ataxia; Limb incoordination; Trunk ataxia; Dysarthria; Abnormal eye movements; Impaired horizontal visual pursuit; Impaired vertical visual pursuit; Dysmetric saccades; Nystagmus; Cerebellar atrophy; Loss of Purkinje cells in the cerebellum

MISCELLANEOUS: One family has been reported (last curated October 2013); Mean age at onset 33 years (range 20-60); Slowly progressive

MOLECULAR BASIS: Caused by mutation in the eukaryotic translation elongation factor-2 gene (EEF2, 130610.0001)
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Cataract - ataxia - deafness

Retrieved: 27-07-2015
Source: Orphanet (Original article)

This syndrome is characterised by mild intellectual deficit, congenital cataract, progressive sensorineural deafness and ataxia. It has been described in two sisters. The inheritance is likely to be autosomal recessive. Last update: October 2006
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Spinocerebellar ataxia 29

Retrieved: 27-07-2015
Source: OMIM (Original article)
Associated genes: itpr1

Description

A number sign (#) is used with this entry because spinocerebellar ataxia-29 (SCA29), also known as congenital nonprogressive cerebellar ataxia (CNPCA), is caused by heterozygous mutation in the ITPR1 gene (147265) on chromosome 3p26-p25.Spinocerebellar ataxia-29 is an autosomal dominant neurologic disorder characterized by onset in infancy of delayed motor development and mild cognitive delay. Affected individuals develop a very slowly progressive or nonprogressive gait and limb ataxia associated with cerebellar atrophy on brain imaging. Additional variable features include nystagmus, dysarthria, and tremor (summary by Huang et al., 2012).

Heterozygous mutation in the ITPR1 gene also causes SCA15 (606658), which is distinguished by later age at onset and normal cognition.

For a general discussion of autosomal dominant spinocerebellar ataxia, see SCA1 (164400).

Clinical features

Tomiwa et al. (1987) reported affected mother and daughter with nonprogressive congenital cerebellar ataxia and normal intelligence. Computed tomography revealed localized atrophy of the cerebellar vermis. Kattah et al. (1983) described a family in which 5 members had primary position vertical nystagmus.

Fenichel and Phillips (1989) described a family in which 4 persons in 3 generations had nonprogressive ataxia from birth. Magnetic resonance imaging in 1 child showed hypoplasia or partial aplasia of the cerebellar vermis. Patients had delayed motor development, truncal ataxia, nystagmus, and normal intelligence. Fenichel and Phillips (1989) were impressed with the fact that 12 of 14 reported persons were female and that 2 affected males were more severely affected than were their female relatives. This led them to suggest both X-linked dominant and autosomal dominant inheritance as possibilities. Rivier and Echenne (1992) described a mother and her 2 daughters with congenital, nonprogressive cerebellar ataxia and atrophy of the cerebellar vermis. Slowly progressive improvement of motor abilities in all 3 patients was an unusual feature. Imamura et al. (1993) described a mother and daughter with early-onset nonprogressive cerebellar ataxia. The mother had a broad-based unsteady gait with frequent falling dating from the first years of life. She had cerebellar signs, including bilateral horizontal nystagmus. MRI at the age of 29 demonstrated increased sulcation of the cerebellar h...

Symptoms

INHERITANCE: Autosomal dominant

HEAD AND NECK: [Eyes]; Nystagmus; Saccadic eye movements

NEUROLOGIC: [Central nervous system]; Cerebellar ataxia, nonprogressive; Delayed motor development; Broad-based gait; Limb ataxia; Dysarthria; Dysdiadochokinesis; Intention tremor; Dysmetria; Nystagmus; Cognitive impairment, mild; Atrophy of the cerebellar vermis seen on MRI

MISCELLANEOUS: Onset at birth; Slow or nonprogressive

MOLECULAR BASIS: Caused by mutation in the inositol 1,4,5-triphosphate receptor 1 gene (ITPR1, 147265.0003)
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Spinocerebellar ataxia type 29

Retrieved: 27-07-2015
Source: Orphanet (Original article)
Associated genes: itpr1

Spinocerebellar ataxia type 29 (SCA29) is a rare subtype of autosomal dominant cerebellar ataxia type 1 (ADCA type 1; see this term) characterized by very slowly progressive or non-progressive ataxia, dysarthria, oculomotor abnormalities and intellectual disability. The prevalence is unknown. More than 50 cases have been reported in the literature. SCA29 presents at birth, or shortly, after with manifestations of very slowly progressive or non-progressive gait and limb ataxia causing delayed walking and frequent falling in children. Mild developmental delay, learning difficulties, and language dysfunction are frequently reported. Other manifestations include nystagmus, dysarthria, dysmetria, and dysdiadochokinesia. Affected patients occasionally present with intention tremor, dystonia, and migraine headaches. Although the disease course is not well established, it appears to range from non-progressive or very slowly progressive ataxia (that does not affect ambulation) to progressive disabling ataxia. A slight improvement in cerebellar signs has been reported in some cases over time. SCA29 is due to mutations in the ITPR1 gene (3p26.1), which is equally the causal gene of SCA15 (see this term). SCA29 is inherited autosomal dominantly and genetic counseling is possible. Expert reviewer(s) Dr Shinsuke FUJIOKA Dr Zbigniew WSZOLEK Last update: November 2014
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Spinocerebellar ataxia type 18

Retrieved: 27-07-2015
Source: Orphanet (Original article)
Associated genes: cyp11b2, sca18

Spinocerebellar ataxia type 18 (SCA18) is a very rare subtype of type I autosomal dominant cerebellar ataxia (ADCA type I; see this term). It is characterized by sensory neuropathy and cerebellar ataxia. Prevalence is unknown. Only 26 cases in a 5-generation American family of Irish ancestry have been reported to date. Onset is in the 2nd and 3rd decades of life with symptomatic onset ranging from 13 to 27 years. Patients initially present with axonal sensory neuropathy, while cerebellar ataxia and motor neuron dysfunction develop later. SCA18 has been linked to chromosome 7q22-q23 but the responsible gene mutation has not yet been identified. Both SCA3 and SCA4 are also associated with a peripheral neuropathy and should be taken into account in the differential diagnosis. Prognosis is unclear. However, mean disease duration from age at onset of illness to age at last examination is about 24 years in the reported cases. Expert reviewer(s) Dr Shinsuke FUJIOKA Dr Nathaniel WHALEY Dr Zbigniew WSZOLEK Last update: May 2011
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Episodic ataxia

Retrieved: 27-07-2015
Source: GHR (Original article)

What is episodic ataxia?

Episodic ataxia is a group of related conditions that affect the nervous system and cause problems with movement. People with episodic ataxia have recurrent episodes of poor coordination and balance (ataxia). During these episodes, many people also experience dizziness (vertigo), nausea and vomiting, migraine headaches, blurred or double vision, slurred speech, and ringing in the ears (tinnitus). Seizures, muscle weakness, and paralysis affecting one side of the body (hemiplegia) may also occur during attacks. Additionally, some affected individuals have a muscle abnormality called myokymia during or between episodes. This abnormality can cause muscle cramping, stiffness, and continuous, fine muscle twitching that appears as rippling under the skin. Episodes of ataxia and other symptoms can begin anytime from early childhood to adulthood. They can be triggered by environmental factors such as emotional stress, caffeine, alcohol, certain medications, physical activity, and illness. The frequency of attacks ranges from several per day to one or two per year. Between episodes, some affected individuals continue to experience ataxia, which may worsen over time, as well as involuntary eye movements called nystagmus. Researchers have identified at least seven types of episodic ataxia, designated type 1 through type 7. The types are distinguished by their pattern of signs and symptoms, age of onset, length of attacks, and, when known, genetic cause.

How common is episodic ataxia?

Episodic ataxia is uncommon, affecting less than 1 in 100,000 people. Only types 1 and 2 have been identified in more than one family, and type 2 is by far the most common form of the condition.

What genes are related to episodic ataxia?

Episodic ataxia can be caused by mutations in several genes that play important roles in the nervous system. Three of these genes, KCNA1, CACNA1A, and CACNB4, provide instructions for making proteins that are involved in the transport of charged atoms (ions) across cell...

Keywords

episodic ataxia,Ataxia,Pathological Conditions, Signs and Symptoms,Nervous System Diseases,Signs and Symptoms,Neurologic Manifestations,Dyskinesias,Movement Disorders,Central Nervous System Diseases,Brain and nervous system,periodic vestibulocerebellar ataxia,CACNA1A,CACNA1A gene,CACNB4,CACNB4 gene,KCNA1,KCNA1 gene,SLC1A3,SLC1A3 gene,EA,National Library of Medicine,NLM,National Institutes of Health,NIH,health problem,health problems,disease,diseases,human genetics,gene,genes,genetic disease,genetic conditions,genetic disorders,medical genetics,genetics education,genetics glossary,gene reference,genetics reference,human genetic health,genomic medicine,molecular medicine,genetic testing,genomic medicine,gene therapy,pharmacogenomics,genetic counseling,counseling,gene testing,genome,hereditary family history,future of medicine,Disease and Gene Association,congenital,heritable disorders,inherited disorders,heritable diseases,inherited diseases,family disorders,family diseases,inborn disorders,inborn diseases
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Early-onset cerebellar ataxia with retained tendon reflexes

Retrieved: 27-07-2015
Source: Orphanet (Original article)
Associated genes: pdyn

Early onset cerebellar ataxia with retained reflexes (EOCARR) or Harding ataxia is a cerebellar ataxia characterized by the progressive association of a cerebellar and pyramidal syndrome with progressive cerebellar ataxia, brisk tendon reflexes, and sometimes profound sensory loss. The prevalence of EOCARR ataxia has been estimated to be around 1/100,000, and the birth prevalence at 1/48,000 births in North-western Italy. EOCARR is a progressive cerebellar ataxia, with disease onset occurring in childhood or in juveniles (ranging from 3 to 20 years with a mean age of 9 years). The disease develops within the first two decades of life. EOCARR is characterized by dysarthria, gait ataxia, nystagmus, brisk tendon reflexes in the upper and lower limbs, absent ankle reflexes, and discrete or absent deep sensory loss. The association of brisk jerks and absent ankle reflexes may occur. Oculomotor disturbances, dysphagia, tremor, scoliosis, pes cavus, extensor plantar response, and lower limb wasting and weakness may be observed while amyotrophy is rarely observed. Moreover, spasticity may become progressively severe. The exact etiology of EOCARR is still unknown. However, molecular genetic analysis in a Tunisian family confirmed the genetic heterogeneity of this syndrome and mapped the gene locus to chromosome 13q11-12. Diagnosis relies on physical examination as well as on imaging findings (magnetic resonance imaging (MRI) or computed tomography (CT)) revealing cerebellar atrophy. Peripheral nerve conduction and nerve biopsy findings may show moderate to severe axonal sensory-motor neuropathy with axonal regeneration. Differential diagnosis includes Friedreich ataxia (FRDA; in contrast to EOCARR shows cardiomyopathy, diabetes mellitus, scoliosis, skeletal deformities or optic atrophy), autosomal dominant cerebellar ataxia (ADCA), autosomal recessive spastic ataxia of Charlevoix-Saguenay, ataxia with vitamin E deficiency (see these terms), and inherited metabolic d...
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Nystagmus 4, congenital, autosomal dominant

Retrieved: 27-07-2015
Source: OMIM (Original article)
Associated genes: cyp11b2, nys4

Description

Classic congenital or infantile nystagmus presents as conjugate, horizontal oscillations of the eyes, in primary or eccentric gaze, often with a preferred head turn or tilt. Other associated features may include mildly decreased visual acuity, strabismus, astigmatism, and occasionally head nodding. Eye movement recordings reveal that infantile nystagmus is predominantly a horizontal jerk waveform, with a diagnostic accelerating velocity slow phase. However, pendular and triangular waveforms may also be present. The nystagmus may rarely be vertical. As these patients often have normal visual acuity, it is presumed that the nystagmus represents a primary defect in the parts of the brain responsible for ocular motor control; thus the disorder has sometimes been termed 'congenital motor nystagmus' (Tarpey et al., 2006; Shiels et al., 2007).

For a discussion of genetic heterogeneity of congenital nystagmus, see NYS1 (310700).

Clinical features

Harris et al. (1993) reported an unusual eye movement abnormality in 10 members of an English Caucasian family. The proband was a 7-year-old boy whose mother had been diagnosed with neurofibromatosis I (NF1; 162200) and who himself had cutaneous signs of the disorder and Lisch nodules of the irides. In addition, however, he had gaze-paretic nystagmus, rebound nystagmus, and saccadic pursuit. Despite these vestibulocerebellar ocular motor signs, he had no ataxia and magnetic resonance imaging of the brain showed no abnormality. Similar eye movement abnormalities but no stigmata of NF1 were found in the father, a younger sister, and 7 other paternal relatives, whereas the mother had normal eye movements. Harris et al. (1993) concluded that the boy inherited NF1 from his mother and the eye movement abnormality, which was unrelated, from the father. The onset of the disorder was in early childhood. Seven patients who were examined showed no tremor, dizziness, consistent ataxia, or other cerebellar signs that are often associated with these oculomotor deficits, and, apart from strabismus, the patients were asymptomatic. After childhood, there appeared to be no progression; the oldest affected member was 40 years of age. Two members had been prone to falling in childhood, and 1 admitted to dizziness when tired. Harris et al. (1993) concluded that the disorder represented a benign and previously undescribed condition. The pedigree contained one instance of male-to-male transmission, suggesting autosomal dominant inheritance.

Ragge et al. (2003) provided follow-up on the family reported by Harris et al. (1993). There ...

Symptoms

INHERITANCE: Autosomal dominant

HEAD AND NECK: [Eyes]; Strabismus; Nystagmus

NEUROLOGIC: [Central nervous system]; Poor vestibuloocular reflex; Upbeat nystagmus; Gaze-evoked nystagmus; Poor or absent smooth pursuit; Dizziness may occur; Loss of balance may occur; Cerebellar origin most likely

MISCELLANEOUS: Onset within first 2 years; Nonprogressive
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Spinocerebellar ataxia type 34

Retrieved: 27-07-2015
Source: Orphanet (Original article)

Spinocerebellar ataxia type 34 (SCA34) is a subtype of autosomal dominant cerebellar ataxia type 1 (ADCA type 1; see this term), characterized by papulosquamous, ichthyosiform plaques on the limbs appearing shortly after birth and later manifestations including progressive ataxia, dysarthria, nystagmus and decreased reflexes. SCA34 has been reported in 25 members of one French-Canadian family to date. Disease onset occurs shortly after birth with the appearance of papulosquamous, ichthyosiform plaques on the limbs, which are often only present in the winter. After the age of 25 they tend to disappear completely. Progressive ataxia, dysarthria, decreased reflexes, and nystagmus are further clinical signs of the disease that occur after the onset of skin manifestations, generally in the third to fourth decade of life. Cerebellar and pontine atrophy is visible with magnetic resonance imaging (MRI) in individuals who develop cerebellar ataxia. SCA34 is due to a mutation in the ELOVL4 gene (6q14). SCA34 is inherited in an autosomal dominant manner and genetic counseling is possible. Expert reviewer(s) Dr Shinsuke FUJIOKA Dr Zbigniew WSZOLEK Last update: June 2014
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Spinocerebellar ataxia, x-linked 5

Retrieved: 27-07-2015
Source: OMIM (Original article)
Associated genes: cyp11b2, scax5

Clinical features

For a discussion of genetic heterogeneity of X-linked spinocerebellar ataxia (SCAX), see SCAX1 (302500).Zanni et al. (2008) reported a large American family of Norwegian descent in which 6 males spanning 3 generations had spinocerebellar ataxia inherited in an X-linked recessive pattern. All had a similar clinical phenotype with neonatal hypotonia, delayed motor development, nonprogressive ataxia, nystagmus, and dysarthria appearing in the first year of life. The symptoms tended to improve with age, and all eventually walked without support. Intelligence was normal. Neuroimaging showed global cerebellar hypoplasia without evidence of supratentorial anomalies.

Mapping

By linkage analysis of a large family with X-linked spinocerebellar ataxia, Zanni et al. (2008) identified a candidate locus, referred to here as SCAX5, on Xq25-q27.1 (maximum 2-point lod score of 3.44 at DXS1192.) Haplotype analysis delineated a 12-cM interval between markers DXS1047 and DXS1227 (multipoint lod score of 4.11). Sequence analysis excluded mutations in the coding regions of the FGF13 (300070) and ZIC3 (300265) genes. The clinical and neuroradiologic findings were very similar to those described in SCAX1 (Illarioshkin et al., 1996; Bertini et al., 2000); however, the SCAX5 locus did not overlap with the SCAX1 locus.

Symptoms

INHERITANCE: X-linked recessive

HEAD AND NECK: [Eyes]; Nystagmus

NEUROLOGIC: [Central nervous system]; Delayed motor development; Hypotonia, neonatal; Dysarthria; Ataxia; Action tremor; Normal intelligence

MISCELLANEOUS: Onset in infancy; Nonprogressive disorder; Symptoms tend to improve with age; Patients achieve ambulation
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Spinocerebellar ataxia type 1

Retrieved: 27-07-2015
Source: Orphanet (Original article)

Spinocerebellar ataxia type 1 (SCA1) is a subtype of type I autosomal dominant cerebellar ataxia (ADCA type I; see this term) characterized by dysarthria, writing difficulties, limb ataxia, and commonly nystagmus and saccadic abnormalities. Prevalence is estimated to be 1-2 in 100,000 with significant geographical and ethnic variations. The disease typically presents in the 4th decade (age range = 4-74 years). Ataxia gradually progresses and additional features may emerge including proprioceptive loss, hypoactive reflexes, ophthalmoparesis, and mild optic neuropathy. Initial presentation with blepharospasm, oromandibular dystonia, and retrocollis preceding ataxia has been reported. Cognition is relatively spared early on; however, executive dysfunction and impaired verbal memory may develop in later stages. SCA1 is caused by CAG repeat expansions in the ATXN1 gene region on chromosome 6p23. Prognosis is poor. In the late stages of the disease, usually 10 to 15 years following onset, bulbar dysfunction secondary to affection of lower medullary nuclei results in aspiration which is life-threatening. Expert reviewer(s) Dr Shinsuke FUJIOKA Dr Nathaniel WHALEY Dr Zbigniew WSZOLEK Last update: May 2011
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Benign paroxysmal positional vertigo

Retrieved: 27-07-2015
Source: WIKIPEDIA (Original article)
Associated genes: bppv
Benign paroxysmal positional vertigo Benign paroxysmal positional vertigo (BPPV) is a disorder arising in the inner ear. Its symptoms are repeated episodes of positional vertigo, that is, of a spinning sensation caused by changes in the position of the head. BPPV is the most common cause of the symptoms of vertigo.http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0002393/

Classification

Vertigo, a distinct process sometimes confused with dizziness, accounts for about 6 million clinic visits in the U.S. every year, and 17–42% of these patients eventually are diagnosed with BPPV. Other causes of vertigo include: Motion sickness/motion intolerance: a disjunction between visual stimulation, vestibular stimulation, and/or proprioception Visual exposure to nearby moving objects (examples of optokinetic stimuli: passing cars, falling snow) Other diseases: (labyrinthitis, Ménière's disease, migraine.Buchholz, D. Heal Your Headache. New York:Workman Publishing;2002:74-75 etc.)

Signs and symptoms

Symptoms Vertigo: Spinning dizziness, which must have a rotational component. Short duration (paroxysmal): Lasts only seconds to minutes Positional in onset: Can only be induced by a change in position. Nausea is often associated Visual disturbance: It may be difficult to read or see during an attack due to associated nystagmus. Pre-syncope (feeling faint) or syncope (fainting) is unusual. Emesis (vomiting) is uncommon but possible. Signs Rotatory (torsional) nystagmus, where the top of the eye rotates towards the affected ear in a beating or twitching fashion, which has a latency and can be fatigued (the vertigo should lessen with deliberate repetition of the provoking maneuver). Nystagmus should only last for 30 seconds to one minute. Patients do not experience other neurological deficits such as numbness or weakness, and if these symptoms are present, a more serious etiology such as posterior circulation stroke or ischemia, must be considered. The spinning sensation experienced from BPPV is usually triggered by movement of the head, will have a sudden onset, and can last anywhere from a few seconds to several minutes. The most common movements patients report triggering a spinning sensation are tilting their head upwards in order to look at something, and rolling over in bed.

Cause

Within the labyrinth of the inner ear lie collections of calci...

Diagnosis

The condition is diagnosed by the patient's history, and by performing the Dix-Hallpike maneuver and/or the roll test.Schubert, M. C. (2007). Vestibular Disorders. In S. O’Sullivan & T. Schmitz (Eds.), Physical Rehabilitation (5th ed.) (pp. 999-1029). Philadelphia: F.A. Davis Company. Patients with BPPV will report a history of vertigo as a result of fast head movements. Many patients are also capable of describing the exact head movements that provokes their vertigo. The Dix-Hallpike test is a common test performed by examiners to determine whether the posterior semicircular canal is involved. It involves a reorientation of the head to align the posterior semicircular c...
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Spinocerebellar ataxia type 6

Retrieved: 27-07-2015
Source: GARD (Original article)

Spinocerebellar ataxia type 6

Spinocerebellar ataxia type 6 (SCA6) is a neurological condition characterized by progressive problems with movement. Initial symptoms include problems with coordination and balance (ataxia). Other early signs and symptoms include speech difficulties (dysarthria), involuntary eye movements (nystagmus), and double vision. Over time, individuals with SCA6 may develop loss of coordination in their arms, tremors, and uncontrolled muscle tensing (dystonia). The signs and symptoms of SCA6 typically begin in a person's forties or fifties. Most people with this disorder require wheelchair assistance by the time they are in their sixties. Spinocerebellar ataxia type 6 is caused by mutations in the CACNA1A gene. This condition is inherited in an autosomal dominant pattern
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Spinocerebellar ataxia 38

Retrieved: 27-07-2015
Source: OMIM (Original article)

Description

A number sign (#) is used with this entry because spinocerebellar ataxia-38 (SCA38) is caused by heterozygous mutation in the ELOVL5 gene (611805) on chromosome 6p12.Spinocerebellar ataxia-38 is an autosomal dominant neurologic disorder characterized by adult-onset of slowly progressive gait ataxia accompanied by nystagmus. Brain MRI shows cerebellar atrophy (summary by Di Gregorio et al., 2014).

For a general discussion of autosomal dominant spinocerebellar ataxia, see SCA1 (164400).

Clinical features

Di Gregorio et al. (2014) reported 4 unrelated families, 3 Italian and 1 French, with a relatively pure form of autosomal dominant spinocerebellar ataxia. Patients presented with walking difficulties due to gait ataxia between 34 and 51 years of age. Additional features included nystagmus, slow saccades, dysarthria, and limb ataxia. The disorder was slowly progressive. Several patients had distal sensory impairment consistent with axonal neuropathy. Cognition was preserved.

Inheritance

The transmission pattern in the families with SCA38 reported by Di Gregorio et al. (2014) was consistent with autosomal dominant inheritance.

Mapping

By genomewide linkage analysis of a large Italian family with autosomal dominant SCA, Di Gregorio et al. (2014) found linkage to a 56.2-Mb interval on chromosome 6p22.2-q14.1 between markers D6S276 and D6S460 (Zmax of 3.08).

Molecular genetics

In affected members of a large Italian family with autosomal dominant SCA38, Di Gregorio et al. (2014) identified a heterozygous missense mutation in the ELOVL5 gene (G230V; 611805.0001). The mutation was found by linkage analysis and candidate gene sequencing. Screening of the ELOVL5 gene in 456 European probands with SCA identified heterozygous mutations in 3 additional families (611805.0001 and 611805.0002). Arachidonic acid and docosahexaenoic acid, 2 final products of the enzyme, were reduced in the serum of affected individuals. Transfection of the mutations into several cell lines showed that the mutant proteins had a less diffuse ER signal compared to wildtype, and tended to accumulate in the Golgi apparatus. Transfected cells showed increased levels of CHOP (DDIT3; 126337), suggesting activation of the unfolded protein response that could lead to apoptosis.

Population genetics

Di Gregorio et al. (2014) identified the same ELOVL5 mutation (G230V; 611805.0001) in affected members of 3 unrelated Italian families with SCA38. Haplotype analysis indicated a founder effect.

Symptoms

INHERITANCE: Autosomal dominant

HEAD AND NECK: [Eyes]; Nystagmus; Slow saccades

NEUROLOGIC: [Central nervous system]; Cerebellar ataxia; Gait ataxia; Limb ataxia; Dysarthria; Cerebellar atrophy; [Peripheral nervous system]; Axonal neuropathy (in some patients)

MISCELLANEOUS: Onset between 34 and 51 years of age; Slowly progressive

MOLECULAR BASIS: Caused by mutation in the elongation of very long chain fatty acids-like 5 gene (ELOVL5, 611805.0001)
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Cerebellar ataxia, neuropathy, and vestibular areflexia syndrome

Retrieved: 27-07-2015
Source: OMIM (Original article)

Description

Cerebellar ataxia, neuropathy, and vestibular areflexia syndrome (CANVAS) is an adult-onset slowly progressive neurologic disorder characterized by imbalance due to cerebellar gait and limb ataxia, impaired vestibular function bilaterally, and non-length-dependent sensory neuropathy (summary by Szmulewicz et al., 2011).

Clinical features

Migliaccio et al. (2004) reported 4 unrelated patients, 2 males and 2 females, with a syndrome comprising cerebellar ataxia and bilateral vestibulopathy with impaired ability of the eye velocity to match head velocity. All had a characteristic sign on clinical examination: impairment of the visually enhanced vestibuloocular reflex (VVOR), or 'doll's head reflex,' in which a normal individual shows compensatory saccades when the head is slowly and smoothly oscillated from side to side while trying to view an earth-fixed target straight ahead. None of the patients had a family history of a similar disorder. Each patient presented between 50 and 60 years of age with slowly increasing gait ataxia and later developed dysarthria. All had problems standing and showed a positive Romberg test. Limb ataxia was less prominent. Detailed vestibuloocular testing showed impaired smooth pursuit, impaired vestibuloocular reflex, and impaired optokinetic reflex. Gaze-evoked nystagmus was present under certain conditions. Three patients had clinical and electrophysiologic evidence of a sensory peripheral neuropathy. Sural nerve biopsy of 1 patient showed a severe axonal neuropathy. None had extrapyramidal features. Brain MRI showed cerebellar atrophy. Genetic testing for several common spinocerebellar ataxias (see, e.g., SCA1, 164400) was negative.

Szmulewicz et al. (2011) reported retrospective data on 27 patients, including the 4 reported by Migliaccio et al. (2004), with a syndrome including cerebellar ataxia, neuropathy, and vestibular areflexia, which they termed 'CANVAS.' The median age at onset was 60 years (range, 33-71), and...

Symptoms

INHERITANCE: Autosomal recessive

HEAD AND NECK: [Ears]; Normal hearing; Loss of vestibular reflexes; Atrophy of vestibular nerves and ganglion cells (ascertained in 1 patient); [Eyes]; Impairment of compensatory eye movement reflexes; Impaired visually enhanced vestibuloocular reflex (VVOR); Impaired vestibuloocular reflex (VOR); Impaired horizontal smooth pursuit; Oscillopsia; Saccadic movements; Gaze-evoked nystagmus

NEUROLOGIC: [Central nervous system]; Imbalance; Cerebellar ataxia; Gait ataxia; Appendicular ataxia; Positive Romberg sign; Dysarthria; Cerebellar atrophy; Loss of cerebellar Purkinje cells; [Peripheral nervous system]; Peripheral neuropathy, sensory; Hyporeflexia; Sensory impairment, non length-dependent; Decreased or absent sensory nerve action potentials, upper and lower limbs; Sural nerve biopsy shows axonal loss

MISCELLANEOUS: Adult onset (sixth decade); Slowly progressive

Retrieved: 27-07-2015
Source: OMIM (original)

Description

Marmor (1973) reported 3 families in 2 of which the mother and 1 or more children were affected. Forsythe (1955) and Dichgans and Kornhuber (1964) described families in which male-to-male transmission was observed. Vertical nystagmus most often signifies acquired disease. The familial disorder is a motor-type vertical (and horizontal) nystagmus with associated mild ataxia. Most of the affected persons had absent optokinetic nystagmus and a hyperactive vestibuloocular response.

Symptoms

Eyes: Vertical nystagmus; Absent optokinetic nystagmus; Hyperactive vestibuloocular response

Neuro: Mild ataxia

Inheritance: Autosomal dominant


Retrieved: 27-07-2015
Source: OMIM (original)

Description

Polizzi et al. (1999) described a 5-year-old Italian boy with hypotonia, congenital nystagmus, ataxia, and abnormal auditory brainstem responses. The authors stated that this was the first Caucasian patient reported with this disorder, which had previously been described in 10 male Oriental patients, 2 of whom were sibs (Wang et al., 1989). Body weight was below the 3rd centile in many of the patients reported.


Retrieved: 27-07-2015
Source: OMIM (original)

Description

In a highly inbred Arab family with ataxia-telangiectasia of complementation group A (ATA; 208900), Ziv et al. (1992) found 3 individuals who had ataxia, hypotonia, microcephaly, and congenital cataracts with nystagmus. Mental retardation was also observed in 1 of the 3 persons. The one individual appeared to be affected with both ataxia-telangiectasia and the AMC syndrome. Findings of the AMC syndrome resembled the Marinesco-Sjogren syndrome (MSS; 248800); however, microcephaly is not part of MSS, and mental retardation was present in only 1 of the AMC patients. Cataract is not characteristic of any of the known disorders that simulate ataxia-telangiectasia. That the AMC syndrome was an entity separate from AT in the Arab family was indicated by linkage studies.

Symptoms

Neuro: Ataxia; Hypotonia; Mental retardation

HEENT: Microcephaly; Congenital cataracts; Nystagmus

Inheritance: Autosomal recessive


Retrieved: 27-07-2015
Source: Orphanet (original)
Associated genes: itpr1

This disease has been moved to Spinocerebellar ataxia type 15/16


Retrieved: 27-07-2015
Source: Orphanet (original)

This syndrome is characterized by of brachydactyly, nystagmus and cerebellar ataxia It has been described in four generations of a family. Intellectual deficit and strabismus are also reported in some patients. Last update: June 2007


Retrieved: 27-07-2015
Source: Orphanet (original)

Episodic ataxia type 4 (EA4) is a very rare form of Hereditary episodic ataxia (see this term) characterized by late-onset episodic ataxia, recurrent attacks of vertigo, and diplopia. Last update: January 2014


Retrieved: 27-07-2015
Source: GARD (original)
Associated genes: tpp1

Spinocerebellar ataxia autosomal recessive 7

Spinocerebellar ataxia autosomal recessive 7, also called SCAR7, is a slowly progressive hereditary form of spinocerebellar ataxia.  Symptoms of SCAR7 can include difficulty walking and writing, speech difficulties (dysarthria), limb ataxia, and a decrease in the size of a region of the brain called the cerebellum (cerebellar atrophy). Of the few reported cases in the literature, some patients also had eye involvement that included nystagmus (in voluntary eye movements) and saccadic pursuit eye movements.  Out of 5 affected siblings examined in a large Dutch family, 2 became wheelchair-dependent late in life. The severity of the symptoms varies from mild to severe.  SCAR7 is caused by mutations in the TPP1 gene and is inherited in an autosomal recessive manner


Retrieved: 27-07-2015
Source: OMIM (original)
Associated genes: syt14

Clinical features

A number sign (#) is used with this entry because this form of autosomal recessive spinocerebellar ataxia, referred to here as SCAR11, is caused by homozygous mutation in the SYT14 gene (610949) on chromosome 1q32.Doi et al. (2011) reported 2 Japanese brothers, born of consanguineous parents, with spinocerebellar ataxia associated with psychomotor retardation. One patient had mild psychomotor retardation since childhood, graduated from a normal junior high school, and held a job for several years, whereas the other had more severe psychomotor retardation, went to a school for the disabled, and later lived in an assisted facility. Both developed a progressive gait disorder in their fifties, followed by dysarthria, limb ataxia, truncal ataxia, and disturbance of smooth eye movements. One had nystagmus. Neither had involuntary movements. Brain MRI showed mild atrophy of the cerebellar vermis and hemispheres.

Inheritance

The transmission pattern in the family reported by Doi et al. (2011) was consistent with autosomal recessive inheritance.

Molecular genetics

By homozygosity mapping followed by whole-exome sequencing in 2 Japanese brothers with autosomal recessive SCA and mild to moderate psychomotor retardation, Doi et al. (2011) identified a homozygous mutation in the SYT14 gene (G484D; 610949.0001).

Symptoms

INHERITANCE: Autosomal recessive

HEAD AND NECK: [Eyes]; Impaired smooth pursuit; Nystagmus (1 patient)

ABDOMEN: [Gastrointestinal]; Dysphagia (1 patient)

NEUROLOGIC: [Central nervous system]; Psychomotor retardation, mild to moderate; Cerebellar ataxia; Limb ataxia; Truncal ataxia; Dysarthria; Cerebellar atrophy

MISCELLANEOUS: Onset of ataxia in the fifties; Slowly progressive; Two Japanese brothers have been reported (as of September 2011)

MOLECULAR BASIS: Caused by mutation in the synaptotagmin 14 gene (SYT14, 610949.0001)


Retrieved: 27-07-2015
Source: OMIM (original)

Clinical features

For a discussion of genetic heterogeneity of spastic ataxia, see SPAX1 (108600).Sanger Brown (1892) described a kindred with 21 persons in 4 generations who showed symmetric ataxia of gait and limb movement, dysarthria, and pyramidal signs in the limbs. Three had impaired pupillary reaction to light; at least 1 developed a disorder of conjugate eye movement. The proband had normal development until age 18 years, when he developed an ataxic gait associated with lower limb weakness and hyperreflexia. Upper limbs became involved later. He also reported dysarthria, dysphagia, and difficulties seeing at a distance. Physical examination as an adult showed significant ataxia, ankle clonus, hyperreflexia, and some abnormal movements suggestive of chorea. Ophthalmic examination showed ptosis, slow pupillary reaction, myopia, optic disc pallor, retinal atrophy, and color blindness. His 26-year-old sister developed ataxia in her twenties and also had poor visual acuity in the light. A brother of the 2 had similar features. In another branch of the family, 3 members had adult onset of progressive ataxia, dysarthria, and poor vision. Nystagmus was not present, but many had optic atrophy.

Dick et al. (1983) described a mother and 3 of her 5 children (2 males, 1 female) with hereditary spastic ataxia combined with congenital miosis. The affected persons were late in walking unaided and had slurred speech, small nonreacting pupils, and nystagmus. Deep tendon reflexes were increased and the plantar reflexes were often extensor.

Timby et al. (2008) reported a Swedish family in which 4 individuals spanning 3 generations had early childhood-onset spastic ataxia and pupillary miosis. Onset of independent walking occurred by age 2 or 3 years, but all showed truncal and gait ataxia. All also had miotic pupils that did not dilate in the dark. Most patients had balance problems and were unable to stand on 1 leg or with closed eyes. Other features included dysdiadochokinesis, hyperreflexia mainly affecting the legs, and mild dysarthria. The ataxia was present from the first years of life, but the miosis started between ages 4 and 16 years.

Inheritance

The transmission pattern of the disorder in the families reported by Brown (1892) and Dick et al. (1983) suggested autosomal dominant inheritance.

Symptoms

INHERITANCE: Autosomal dominant

HEAD AND NECK: [Eyes]; Miosis; Lack of pupillary dilation in the dark; Optic atrophy (in some patients); Nystagmus (in some patients)

NEUROLOGIC: [Central nervous system]; Delayed independent walking; Ataxia, gait; Ataxia, truncal; Dysarthria, mild; Dysdiadochokinesis; Hyperreflexia, lower limbs more than upper limbs

MISCELLANEOUS: Variable age at onset (range childhood to adult)


Retrieved: 27-07-2015
Source: Orphanet (original)
Associated genes: atcay

Cerebellar ataxia, Cayman type is characterised by psychomotor retardation, hypotonia and cerebellar dysfunction (nystagmus, ataxic gait, truncal ataxia, dysarthric speech and intention tremor), associated with cerebellar hypoplasia. The prevalence is unknown, but the disorder is very rare in the general population. However, a founder mutation has led to a high incidence in the Cayman island population. The disorder is transmitted as an autosomal recessive trait and is caused by mutations in the ATCAY gene (19p13.3), encoding Caytaxin. Last update: June 2007


Retrieved: 27-07-2015
Source: Orphanet (original)

Episodic ataxia type 2 (EA2) is the most frequent form of Hereditary episodic ataxia (EA; see this term) characterized by paroxysmal episodes of ataxia lasting hours, with interictal nystagmus and mildly progressive ataxia. Last update: January 2014


Retrieved: 27-07-2015
Source: Orphanet (original)
Associated genes: syne1

This syndrome is characterised by a slowly progressive pure cerebellar ataxia associated with dysarthria. It has been described in 53 individuals from 26 families of Canadian origin. The mode of transmission is autosomal recessive. Positional cloning has led to the identification of several gene mutations. Last update: January 2007


Retrieved: 27-07-2015
Source: GARD (original)
Associated genes: kcnc3

Spinocerebellar ataxia 13

Spinocerebellar ataxia 13 (SCA13) is a rare sub-type of spinocerebellar ataxias, a group of neurological conditions characterized by degeneration of the brain and spinal cord. Signs and symptoms of SCA13 appear to vary among affected people and range from childhood-onset, slowly progressive gait ataxia and dysarthria (often with intellectual disability and occasional seizures) to adult-onset progressive ataxia. Life expectancy is normal. SCA13 is caused by mutations in the KCNC3 gene and is inherited in an autosomal dominant manner. Treatment may include anti-seizure medications; assistive devices (such as a canes and walkers); and/or speech therapy and communication devices


Retrieved: 27-07-2015
Source: OMIM (original)
Associated genes: cacnb4

Clinical features

A number sign (#) is used with this entry because of evidence that episodic ataxia-5 is caused by heterozygous mutation in the CACNB4 gene (601949) on chromosome 2q22-q23.

For a general description and a discussion of genetic heterogeneity of episodic ataxia, see EA1 (160120).Escayg et al. (2000) reported a French Canadian family segregating episodic ataxia. The proband, after age 20 years, experienced recurrent episodes of vertigo and ataxia that lasted for several hours. Interictal examination showed spontaneous downbeat and gaze-evoked nystagmus and mild dysarthria and truncal ataxia. The proband's mother had identical episodes of vertigo and ataxia after age 30 years as well as longstanding dysarthria and imbalance. Acetazolamide prevented the attacks in both the proband and the mother, and the attacks recurred when acetazolamide was briefly discontinued.

Molecular genetics

In affected members of a French Canadian family segregating episodic ataxia, Escayg et al. (2000) identified heterozygosity for a missense mutation in the CACNB4 gene (601949.0002). Herrmann et al. (2005) referred to the form of ataxia caused by mutation in the CACNB4 gene as episodic ataxia type 5.


Retrieved: 27-07-2015
Source: Orphanet (original)
Associated genes: bean1, plekhg4

Spinocerebellar ataxia type 31 (SCA31) is a very rare subtype of autosomal dominant cerebellar ataxia type 3 (ADCA type 3; see this term) characterized by the late-onset of cerebral ataxia, dysarthria, and horizontal gaze nystagmus, and that is occasionally accompanied by pyramidal signs, tremor, decreased vibration sense, and hearing difficulties. SCA31 is the third most common form of ADCA (see this term) in Japan, where more than 20 families have been reported to date. It is rarely found in other Asian countries and is extremely rare in Western countries. The mean age of disease onset is 58 years but it can present between the ages of 8 to 83 years. Ataxia, dysarthria, and horizontal gaze nystagmus are the common manifestations of SCA31 and the disease duration can be more than 10 years. Less common manifestations include pyramidal signs, tremor, decreased vibration sense, and hearing difficulties. SCA31 is due to non-coding pentanucleotide repeat expansions in the brain expressed, associated with NEDD4, 1 (BEAN1) gene (16q21). SCA31 is inherited autosomal dominantly with incomplete penetrance and genetic counseling is possible. Expert reviewer(s) Dr Shinsuke FUJIOKA Dr Zbigniew WSZOLEK Dr Shozaburo YANAMOTO Last update: November 2014

Description

Crouzon (1929) and Sarrouy et al. (1957) reported 2 pairs of sibs with congenital cerebellar hypoplasia. Norman and Urich (1958) noted parental consanguinity in an isolated case. Wichman et al. (1985) reported 3 pairs of affected sibs in unrelated families. All 6 presented within the first 6 months of life with delayed motor and language development. Mathews et al. (1989) also described autosomal recessive cerebellar hypoplasia. Dooley et al. (1992) reported 2 sisters with cerebellar hypoplasia who also had nonprogressive retinal pigmentary disease. They pointed out that 1 of the 2 sibs reported by Mathews et al. (1989) had bilateral retinal pigmentary changes.

It is not certain that the disorder designated cerebellar hypoplasia is distinct from the Norman type of nonprogressive autosomal recessive cerebellar ataxia (213200).

Symptoms

Neuro: Ataxia; Hypotonia; Ataxia; Tremor; Cerebellar hypoplasia

Eyes: Nystagmus

Inheritance: Autosomal recessive


Retrieved: 27-07-2015
Source: Orphanet (original)
Associated genes: cyp11b2, sca30

Spinocerebellar ataxia type 30 (SCA30) is a very rare subtype of autosomal dominant cerebellar ataxia type 3 (ADCA type 3; see this term) characterized by a slowly progressive and relatively pure ataxia. SCA30 has only been described in 6 patients from one Australian family to date. The age of onset ranges from 45 to 76 years with a mean age of onset of 52 years. It presents with oculomotor dysfunction, moderate dysarthria and ataxia that progresses slowly and eventually leads to mobility impairment. Some patients have also reported mild hyperreflexia in the lower limbs. Rarer manifestations include gaze-evoked nystagmus and dystonia. The causal gene has not yet been identified but it has been linked to chromosome 4q34.3-q35.1. SCA30 is inherited in an autosomal dominant manner and genetic counseling is possible. Expert reviewer(s) Dr Shinsuke FUJIOKA Dr Zbigniew WSZOLEK Dr Shozaburo YANAMOTO Last update: November 2014


Retrieved: 27-07-2015
Source: Orphanet (original)

This syndrome is characterized by congenital cerebellar hypoplasia, endosteal sclerosis, hypotonia, ataxia, mild to moderate developmental delay, short stature, hip dislocation, and tooth eruption disturbances. It has been described in four patients. Less common manifestations are microcephaly, strabismus, nystagmus, optic atrophy, and dysarthria. It is appears to be transmitted as an autosomal recessive trait. Last update: June 2007


Retrieved: 27-07-2015
Source: GARD (original)

Spinocerebellar ataxia 5

Spinocerebellar ataxia 5 (SCA5) is one of the many spinocerebellar ataxias, which are inherited conditions that cause degeneration of the spinal cord and cerebellum. SCA5 almost exclusively affects the cerebellum. It is considered to be a mild form that progresses slowly. The age of onset is usually between the ages of 20 and 30, but a wide range in age of onset has been reported. Signs and symptoms may include loss of coordination of the hands, arms, and legs; impaired balance when walking; and slurred speech (dysarthria). SCA5 is caused by mutations in the SPTBN2 gene and is inherited in an autosomal dominant manner


Retrieved: 27-07-2015
Source: WIKIPEDIA (original)
Acute cerebellar ataxia of childhood is a childhood condition characterized by an unsteady gait, most likely secondary to an autoimmune of postinfectious cause, drug induced or paraneoplastic.Brown, Miller. "Pediatrics." Lipincott Williams and Wilkins, 2005, pp 380. Most common virus causing acute cerebellar ataxia are Chickenpox virus and Epstein Barr Virus. It is a diagnosis of exclusion

Epidemiology

Acute cerebellar ataxia is the most common cause of unsteady gait in children. The condition is rare in children older than ten years of age. Most commonly acute cerebellar ataxia affects children between age 18 mo and 7 years.

Etiology

Most common cause of acute cerebellar ataxia is varicella infection. Other viruses include influenza, Epstein-Barr virus, Coxsackie virus, Echo virus or mycoplasma. The possible mechanism is immune complex deposition in the cerebellum.

Clinical features

Acute cerebellar ataxia usually follows 2–3 weeks after an infection. Onset is abrupt. Vomiting may be present at the onset but fever and nuchal rigidity characterestically are absent. Horizontal nystagmus is present is approximately 50% of cases. Truncal ataxia with deterioration of gait Slurred speech and nystagmus Afebrile

Diagnosis

Acute Cerebellar ataxia is a diagnosis of exclusion. Urgent CT scan is necessary to rule out cerebellar tumor or hemorrhage as cause of the ataxia; however in acute cerebellar ataxia, the CT will be normal. CSF studies are normal earlier in the course of disease. Later on CSF shows moderate elevation of proteins.

Management

Supportive treatment is the only intervention for acute cerebellar ataxia of childhood. Symptoms may last as long as 2 or 3 months.

Differential Diagnosis

Brain tumors, including cerebellar astrocytoma, medulloblastoma, neuroblastoma Cerebellar contusion Subdural hematoma Toxins, including ethanol or anticonvulsants Cerebellar infarction or hemorrhage Meningitis Encephalitis Acute disseminated encephalomyelitis Multiple sclerosis

References

See Also http://www.nlm.nih.gov/medlineplus/ency/article/001397.htm