Curry-Jones syndrome is a form of syndromic craniosynostosis characterized by unilateral coronal craniosynostosis or multiple suture synostosis associated with complete or partial agenesis of the corpus callosum, preaxial polysyndactyly and syndactyly of hands and/or feet, along with anomalies of the skin (characteristic pearly white areas that become scarred and atrophic, abnormal hair growth around the eyes and/or cheeks, and on the limbs), eyes (iris colobomas, microphthalmia,) and intestine (congenital short gut, malrotation, dysmotility, chronic constipation, bleeding and myofibromas). Developmental delay and variable degrees of intellectual disability may also be observed. Multiple intra-abdominal smooth muscle hamartomas, trichoblastoma of the skin, occipital meningoceles and development of desmoplastic medulloblastoma have been reported.

Waldenstrom macroglobulinemia is a chronic, slow-growing lymphoproliferative disorder . It usually affects older adults and is primarily found in the bone marrow, although lymph nodes and the spleen may be involved. Affected individuals have a high level of an antibody called immunoglobulin M (IgM) in their blood, which can cause thickening of the blood (hyperviscosity). Although some individuals initially do not have symptoms and are diagnosed from routine blood work, common symptoms may include weakness, appetite loss and weight loss. Other symptoms may include peripheral neuropathy, fever, Raynaud's phenomenon , and mental status changes.

Spastic paraplegia-optic atrophy-neuropathy (SPOAN) syndrome is a rare, complex type of hereditary spastic paraplegia characterized by early-onset progressive spastic paraplegia presenting in infancy, associated with optic atrophy, fixation nystagmus, polyneuropathy occurring in late childhood/early adolescence leading to severe motor disability and progressive joint contractures and scoliosis. SPOAN syndrome is caused by mutations in the KLC2 gene (11q13.1), encoding kinesin light chain 2.

Pili torti-developmental delay-neurological abnormalities syndrome is characterized by growth and developmental delay, mild to moderate neurologic abnormalities, and pili torti. It has been described in a brother and his sister born to consanguineous Puerto Rican parents.

Visual problems are not a prominent feature of this disorder; if present they may be mild and go unrecognized.

Northern epilepsy syndrome Other names Neuronal ceroid lipofuscinosis, Northern epilepsy variant This condition is inherited in an autosomal recessive manner. Northern epilepsy syndrome ( NE ), or progressive epilepsy with mental retardation ( EPMR ), is a subtype of neuronal ceroid lipofuscinosis and a rare disease that is regarded as a Finnish heritage disease . Unlike most Finnish heritage diseases, this syndrome has been reported only in Finland . [1] The disease is characterized by seizures in early childhood that progressively get worse until after puberty. Once the onset of seizures occurs, mental degradation is seen. This continues into adulthood, even after seizure frequency has decreased. The cause of the disease is a missense mutation on chromosome 8 . The creation of a new protein occurs, and the lipid content of the brain is altered because of it.

Northern epilepsy is a rare condition that affects the nervous system. Signs and symptoms of the condition generally develop between ages 5 and 10 years and may include recurrent seizures, mild intellectual disability, and motor abnormalities (i.e. problems with coordination and balance). Some affected people may also experience decreased visual acuity . Northern epilepsy is caused by changes (mutations) in the CLN8 gene and is inherited in an autosomal recessive manner. Treatment options are limited to therapies that can help relieve some of the symptoms.

Clinical description Presentation is typically by 1 year to 2 years of age, but may occur earlier, with myotonia, maske-like facies, short stature, non-progressive muscle weakness, muscle hypertrophy, progressive restriction of range of motion and paucity of subcutaneous tissue. Facial features consist of blepharospasm, progressive blepharophimosis, pursed lips and a puckered chin.

Neonatal Schwartz-Jampel syndrome type 2 (SJS2; 601559), also known as Stuve-Wiedemann syndrome (STWS), is a genetically distinct disorder with a more severe phenotype caused by mutation in the LIFR gene (151443) on chromosome 5p13. Clinical Features Aberfeld et al. (1965) described brother and sister with an apparently progressive disorder characterized by short stature, myotonic myopathy, dystrophy of epiphyseal cartilages, joint contractures, blepharophimosis, unusual pinnae, myopia, and pigeon breast. ... Differentiation from Stuve-Wiedemann syndrome is important because STWS is associated with high mortality. Other Features Viljoen and Beighton (1992) gave an extensive description of SJS and pointed out that malignant hyperthermia is a potentially lethal complication during anesthesia. ... INHERITANCE - Autosomal recessive GROWTH Height - Short stature (postnatal onset) HEAD & NECK Face - Normal face at birth - Sad, fixed facies - Low hairline - Flat face - Full cheeks Ears - Low-set ears - Overfolded helices Eyes - Narrow palpebral fissures - Blepharophimosis - Myopia - Cataract - Microcornea - Long eyelashes in irregular rows - Ptosis Mouth - Small mouth - Pursed lips Neck - Short neck CHEST Ribs Sternum Clavicles & Scapulae - Pectus carinatum ABDOMEN External Features - Umbilical hernia GENITOURINARY External Genitalia (Male) - Inguinal hernia Internal Genitalia (Male) - Small testes SKELETAL - Osteoporosis - Delayed bone age Skull - Small mandible Spine - Platyspondyly - Kyphosis - Kyphoscoliosis - Lumbar lordosis - Coronal cleft vertebrae Pelvis - Hip contracture - Fragmentation of femoral epiphyses - Flattened femoral epiphyses - Coxa vara - Coxa valga - Congenital hip dislocation Limbs - Widened metaphyses - Slender diaphysis - Anterior bowing of long bones - Elbow, knee, shoulder contractures Hands - Wrist contractures - Finger contractures Feet - Toe contractures - Talipes equinovarus - Pes planus SKIN, NAILS, & HAIR Hair - Low hairline - Generalized hirsutism MUSCLE, SOFT TISSUES - Myotonia - Muscular hypertrophy - Muscle weakness - Muscle wasting - EMG - repetitive muscle discharges NEUROLOGIC Central Nervous System - Hyporeflexia - Mental retardation (25%) VOICE - Small, high-pitched voice MISCELLANEOUS - Progressive disease with onset in infancy - Contractures most severe by midadolescence - Anesthesia complications include difficult intubation secondary to microstomia and risk of malignant hyperthermia MOLECULAR BASIS - Caused by mutation in the perlecan gene (HSPG2, 142461.0001 ) ▲ Close

Signs and symptoms may include muscle stiffness and weakness; joint deformities that affect mobility (contractures); short stature; small "fixed" facial features; and eye abnormalities. Previously, SJS was divided into types 1 and 2.

Charcot-Marie-Tooth disease type 1F (CMT1F) is a form of CMT1, with a variable clinical presentation that can range from severe impairment with onset in childhood to mild impairment appearing during adulthood. CMT1F is characterized by a progressive peripheral motor and sensory neuropathy with distal paresis in the lower limbs that varies from mild weakness to complete paralysis of the distal muscle groups, absent tendon reflexes and reduced nerve conduction. CMT1F represents the ''demyelinating'' form of CMT2E and is caused by mutations in the NEFL gene (8p21.2).

A rare axonal hereditary motor and sensory neuropathy characterized by infantile onset of slowly progressive distal motor weakness and atrophy (more severe in legs and moderate in arms) with mildly delayed motor development, hypotonia, and distal sensory impairment of all sensory modalities.

Intellectual deficit (moderate to severe) is a constant feature and is associated with cerebral atrpohy or quadriplegia in some cases.

Identification of biallelic pathogenic variants in TYROBP or TREM2 can confirm the diagnosis if radiographic and clinical features are inconclusive. Management. Treatment of manifestations: Treatment is symptomatic. ... Suggestive Findings PLOSL should be suspected in individuals with the following features: Radiologically demonstrable polycystic osseous lesions and fractures of the wrists and ankles after minor trauma at the mean age of 27 years (range 18-33 years) [Paloneva et al 2001]. ... Option 2 When the diagnosis of PLOSL has not been considered because an individual has atypical phenotypic features, comprehensive genomic testing , which does not require the clinician to determine which gene is likely involved, is an option. ... Histologic examination reveals scattered neurons showing features of central chromatolysis. Intraneuronal or glial pathologic inclusions have not been observed [Paloneva et al 2001].

This article includes a list of general references , but it remains largely unverified because it lacks sufficient corresponding inline citations . Please help to improve this article by introducing more precise citations. ( June 2019 ) ( Learn how and when to remove this template message ) Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy Specialty Medical genetics Causes Mutations in the TREM2 and TYROBP genes Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy is a rare disease characterised by early-onset dementia and multifocal bone cysts. [1] It is also known as Nasu–Hakola disease. Contents 1 Signs and symptoms 2 Genetics 3 Pathopysiology 4 Diagnosis 4.1 Differential diagnosis 4.2 Investigations 5 Treatment 6 Epidemiology 7 History 8 References Signs and symptoms [ edit ] Four stages are recognised in this condition. The first (latent stage) show no symptoms or signs. This stage typically lasts up to the early 20s. This is followed by the osseous stage. This is characterised by recurrent bone pain usually affecting the long bones of the limbs.

Genetic Heterogeneity of Polycystic Lipomembranous Osteodysplasia with Sclerosing Leukoencephalopathy Also see PLOSL2 (618193), cause by mutation in the TREM2 gene (605086) on chromosome 6p21. Clinical Features Hakola (1972) reported a disorder in Finland in which affected patients had onset in the third decade of pain and swelling following strain of the wrist or ankle; fractures occurred after minor accidents. ... Patients usually die between ages 35 and 45, and the later features of the disorder resemble those of Alzheimer disease. ... The disorder was first manifested by multiple bone cysts, with development of a severe neuropsychiatric disorder around the age of 30 years. The typical macroscopic features were marked hydrocephalus ex vacuo due to severe destruction of the white matter, with extensive secondary astrocytic gliosis and relatively better preserved gray matter. ... Verloes et al. (1997) reported a further case and reviewed the epidemiology of clinical features--radiology, pathology, pathophysiology, biochemistry, and differential diagnosis.

Nasu-Hakola disease (NHD), also referred to as polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy (PLOSL), is a rare inherited leukodystrophy characterized by progressive presenile dementia associated with recurrent bone fractures due to polycystic osseous lesions of the lower and upper extremities. Epidemiology Over 200 cases have been reported worldwide in the literature, the majority of them being in the Japanese and Finnish population. The prevalence in Finland is estimated between 1/500,000 and 1/1,000,000. Clinical description The disease course is generally divided into four stages: latent, osseous, early neurologic, and late neurologic. After a normal development during childhood (latent stage), the disease starts manifesting during adolescence or young adulthood (typical age of onset 20-30 years) with pain in the hands, wrists, ankles, and feet.

A rare disorder of pentose phosphate metabolism characterized by developmental delay and intellectual disability, delayed or absent speech, short stature, and congenital heart defects (such as ventricular septal defect, atrial septal defect, and patent foramen ovale). Additional reported features include hypotonia, hyperactivity, stereotypic behavior, ophthalmologic abnormalities (bilateral cataract, uveitis, strabismus), hearing impairment, and variable facial dysmorphism, among others.

Intellectual disability, Buenos-Aires type is a rare intellectual disability syndrome characterized by growth retardation, microcephaly, characteristic facial features (including narrow forehead, bushy eyebrows, hypertelorism, small, downward-slanting palpebral fissures with blepharoptosis, malformed and low-set ears, broad straight nose, thin upper lip, and a wide, tented mouth), developmental delay, intellectual disability, speech disorder, and multiple organ malformations (e.g. ventricular septal defect, megaloureter, dilated renal pelvis).

This article needs additional citations for verification . Please help improve this article by adding citations to reliable sources . Unsourced material may be challenged and removed. Find sources: "CAMFAK syndrome" – news · newspapers · books · scholar · JSTOR ( April 2010 ) ( Learn how and when to remove this template message ) CAMFAK syndrome Other names Cataract-microcephaly-arthrogryposis-kyphosis syndrome, Cataract-microcephaly-failure to thrive-kyphoscoliosis syndrome CAMFAK syndrome has an autosomal recessive pattern of inheritance . CAMFAK syndrome (or CAMAK syndrome ) is an acronym used to describe a rare inherited neurologic disease, characterized by peripheral and central demyelination of nerves, similar to that seen in Cockayne syndrome . [1] The name "CAMFAK" comes from the first letters of the characteristic findings of the disease: ca taracts , m icrocephaly , fa ilure to thrive , and k yphoscoliosis . [2] The disease may occur with or without failure to thrive and arthrogryposis . Contents 1 Presentation 2 Genetics 3 Treatment 4 References 5 External links Presentation [ edit ] Low birth weight and a bird-like face may be the first signs. Severe intellectual deficit and death within the first decade are typical.

A number sign (#) is used with this entry because of evidence that Majeed syndrome (MJDS) is caused by homozygous mutation in the LPIN2 gene (605519) on chromosome 18p11. Clinical Features Majeed et al. (1989) reported 2 brothers and a female cousin who had chronic recurrent multifocal osteomyelitis (CRMO; 259680) and congenital dyserythropoietic anemia (CDA); the brothers also had neutrophilic dermatosis or Sweet syndrome (608068).

Majeed syndrome is characterized by recurrent episodes of fever and inflammation in the bones and skin. The two main features of this condition are chronic recurrent multifocal osteomyelitis (CRMO) and congenital dyserythropoietic anemia (CDA).

Majeed syndrome Specialty Dermatology Majeed syndrome is an inherited skin disorder characterized by chronic recurrent multifocal osteomyelitis , congenital dyserythropoietic anemia and a neutrophilic dermatosis. [1] It is classified as an autoinflammatory bone disorder. The condition is found in people with two defective copies (autosomal recessive inheritance) of the LPIN2 gene. LPIN2 encodes lipin-2 which is involved in lipid metabolism. The pathogenesis of this mutation with the clinical manifestations has not been elucidated. [2] See also [ edit ] TNF receptor associated periodic syndrome List of cutaneous conditions References [ edit ] ^ Rapini, Ronald P.; Bolognia, Jean L.; Jorizzo, Joseph L. (2007). Dermatology: 2-Volume Set . St. Louis: Mosby. ISBN 978-1-4160-2999-1 . ^ "Majeed syndrome" . Genetics Home Reference . Retrieved 17 April 2018 . External links [ edit ] Orphanet syndrome Majeed syndrome This dermatology article is a stub .

Majeed syndrome is a rare genetic multisystemic disorder characterized by chronic recurrent multifocal osteomyelitis, congenital dyserythropoietic anemia, which may be accompanied by neutrophilic dermatosis. Epidemiology The syndrome is extremely rare. Fourteen cases born into consanguineous families, from the Middle East, India and Spain have been reported. Clinical description Onset is generally within the first two years of life although it may present later in childhood (range 1 month to 8 years) as bone pain. Chronic recurrent multifocal osteomyelitis (CRMO) associated with Majeed syndrome is typically more severe than that of non-syndromic CRMO, and is more persistent, with short remissions and more frequent exacerbations. It can be associated with fever, joint pain, delayed bone age, growth failure, short adult stature, and development of flexion contractures.

Hypertelorism-hypospadias-polysyndactyly syndrome is a very rare syndrome associating an acro-fronto-facio-nasal dysostosis with genitourinary anomalies. Epidemiology It has been described in three families. Clinical description Craniofacial manifestations include wide anterior fontanel, flat occiput, hypertelorism, ptosis, proptosis, broad nasal bridge and nasal tip, long philtrum and posteriorly rotated or low set ears. Hypospadias and shawl scrotum are present in all males. Acral manifestations include syndactyly of fingers, broad thumbs or halluces or preaxial polydactyly. The affected patients have no intellectual deficit. Genetic counseling The condition seems to be hereditary, and transmitted as an autosomal recessive trait.

Prevalence The prevalence of ethylmalonic encephalopathy is unknown. More than 80 individuals with features consistent with EE and a molecularly confirmed diagnosis have been reported [Tiranti et al 2004, Tiranti et al 2006, Mineri et al 2008]. ... Defects of the mitochondrial electron-transfer flavoprotein pathway or glutaric aciduria type II Some forms of respiratory chain deficiency Of note, brain vascular lesions appear to be a specific neuropathologic feature of EE, not seen in other forms of ethylmalonic aciduria or in disorders caused by primary respiratory chain defects such as Leigh syndrome [Giordano et al 2012, Tiranti & Zeviani 2013].

Ethylmalonic encephalopathy (EE) causes damage to the brain, nerves, and blood vessels. Symptoms are present at birth and tend to get worse over time. These include low muscle tone, spasms of the arms and legs, seizures, and developmental delay. Blood vessel damage causes tiny red spots under the skin ( petechiae ) and blue discoloration in the hands and feet due to reduced blood flow ( acrocyanosis ). Chronic bloody diarrhea and difficulty swallowing leads to poor growth. EE is considered a lethal condition, and most people die in childhood.

Death usually occurs in the first decade of life (summary by Drousiotou et al., 2011). Clinical Features Burlina et al. (1991) first described ethylmalonic encephalopathy as a syndrome characterized by developmental delay, acrocyanosis, petechiae, and chronic diarrhea. ... Animal Model Tiranti et al. (2009) found that Ethe1-null mice developed the cardinal features of ethylmalonic encephalopathy, including poor growth, reduced motor activity, early death, low cytochrome c oxidase (COX) in muscle and brain, and increased urinary excretion of ethylmalonic acid. ... The toxic effects of this accumulation can account for several features, including ethylmalonic aciduria, COX deficiency, microangiopathy, acrocyanosis, and chronic diarrhea.

However, more cases need to be identified before it can be determined whether milder cases of EE exist with clinical features like MADD or SCADD. In the absence of any detectable ETHE1 gene mutation, molecular analysis should include sequencing of the SCAD gene (mutations in which lead to SCADD) and, eventually, of the two electron transfer flavoprotein ( ETFA and ETFB ) genes and the ETFDH gene (one of which may carry mutations in patients with MADD).

Chronic diarrhea is another common feature of ethylmalonic encephalopathy. [3] EE is often identified by urine organic acid analysis, the excretion of ethylmalonic acid, methylsuccinic acid, isobutyrylglycine and isovalerylglucine. ... It remains unclear how a loss of the ETHE1 enzyme leads to progressive brain dysfunction and the other features of ethylmalonic encephalopathy.