A number sign (#) is used with this entry because gray platelet syndrome (GPS) is caused by homozygous or compound heterozygous mutation in the NBEAL2 gene (614169) on chromosome 3p21. Description The gray platelet syndrome (GPS) is a rare inherited disorder characterized by mild to moderate bleeding tendency, moderate thrombocytopenia, and a marked decrease or absence of platelet alpha-granules and of the proteins contained in alpha-granules. The platelets are enlarged, but not giant, and have a gray appearance on light microscopy of Wright-stained peripheral blood smears due to decreased granules. Many patients with gray platelet syndrome develop a stable myelofibrosis (summary by Nurden and Nurden, 2007). Cases suggesting autosomal dominant and autosomal recessive inheritance have been described, indicating that GPS is probably a genetically heterogeneous disorder with more than one molecular cause.

Gray platelet syndrome (GPS) is a rare inherited bleeding disorder characterized by macrothrombocytopenia, myelofibrosis, splenomegaly and typical gray appearance of platelets on Wright stained peripheral blood smear. Epidemiology Exact prevalence of the disorder is not known. About 60 cases from various populations around the world have been described in the literature to date. It affects males and females equally. Clinical description Onset of clinical symptoms is generally in the neonatal period or in early childhood while age of diagnosis is variable. Presenting features include low platelet counts, easy bruising (petechiae), prolonged bleeding and epistaxis. Patients often have myelofibrosis and splenomegaly. Bleeding tendency is usually mild to moderate in GPS patients with mild thrombocytopenia.

A number sign (#) is used with this entry because of evidence that platelet-type bleeding disorder-17 (BDPLT17) is caused by heterozygous mutation in the GFI1B gene (604383) on chromosome 9q34. Description Platelet-type bleeding disorder-17 is an autosomal dominant disorder characterized by increased bleeding tendency due to abnormal platelet function. It is a type of 'gray platelet syndrome' because the platelets appear abnormal on light microscopy. Electron microscopy shows decreased or absent alpha-granules within platelets, and bone marrow biopsy shows increased numbers of abnormal megakaryocytes, suggesting a defect in megakaryopoiesis and platelet production. The bleeding severity is variable (summary by Monteferrario et al., 2014).

Gray platelet syndrome (GPS) is a rare inherited bleeding disorder characterized by platelets that have a gray appearance, severe thrombocytopenia, myelofibrosis , and splenomegaly . About 60 cases from various populations around the world have been described in the literature to date. GPS results from the absence or reduction of alpha-granules in platelets, which store proteins that promote platelet adhesiveness and wound healing when secreted during an injury. GPS is caused by mutations in the NBEAL2 gene and inherited in an autosomal recessive manner.

Gray platelet syndrome is a bleeding disorder associated with abnormal platelets, which are small blood cells involved in blood clotting. People with this condition tend to bruise easily and have an increased risk of nosebleeds (epistaxis). They may also experience abnormally heavy or extended bleeding following surgery, dental work, or minor trauma. Women with gray platelet syndrome often have irregular, heavy periods (menometrorrhagia). These bleeding problems are usually mild to moderate, but they have been life-threatening in a few affected individuals.

Linear atrophoderma of Moulin (LAM) is characterized by mildly atrophic and hyperpigmented band-like lesions that follow the lines of Blaschko on the trunk or limbs. Since its initial description in 1992, less than 30 cases have been reported in the literature. Onset occurs during childhood or adolescence and the disease is non-progressive. There is no prior inflammation or subsequent scleroderma. The aetiology is unknown but as LAM follows the lines of Blaschko it has been suggested that the disease is caused by mosaicism of a predisposing gene.

Urachal sinus is a type of congenital urachal anomaly (see this term) resulting from the failure of the umbilical end of the urachus to close, without continuity to the bladder, and that is usually asymptomatic but can present with continuous cloudy umbilical discharge, tender midline infraumbilical mass and fever when infected.

Verhagen et al. (1988) described a family with vestibular areflexia and progressive hearing loss developing from the age of about 40 years onward and displaying a pattern of autosomal dominant inheritance. Verhagen and Huygen (1991) reported the same disorder in a member of the family previously thought to be unaffected at the age of 42 years. At the age of 47 years she showed progressive hearing loss and left-sided tinnitus as well as head movement-dependent oscillopsia and instability in the dark. Inheritance - Autosomal dominant Neuro - Head movement-dependent oscillopsia and dark instability Ears - Vestibular areflexia - Progressive hearing loss - Tinnitus ▲ Close

Morgagni-Stewart-Morel (MSM) syndrome is a disorder characterized by thickening of the frontal bone of the skull (hyperostosis frontalis interna), as well as obesity and excessive hair growth (hypertrichosis). Other signs and symptoms may include seizures, headaches, diabetes insipidus , and sex gland disturbances. The cause of Morgagni-Stewart-Morel syndrome is not fully understood. Some instances of dominant inheritance have been reported, but whether it is autosomal dominant or X-linked dominant is not known. Treatment may include medication for headaches and seizures and surgery to remove the excessive bone of the skull.

A rare cranial malformation characterized by hyperostosis frontalis interna, variably associated with metabolic and endocrine disorders (such as obesity, diabetes mellitus, and hirsutism, among others). Compression by calvarial thickening may lead to cerebral atrophy and present with cognitive impairment, neuropsychiatric symptoms, headaches, and epilepsy. The condition predominantly affects women.

Hyperostosis frontalis interna Hyperostosis frontalis interna in a 74-year-old woman Specialty Radiology Hyperostosis frontalis interna is a common, benign thickening of the inner side of the frontal bone of the skull . It is found predominantly in women after menopause and is usually asymptomatic. Mostly frequently it is found as an incidental finding discovered during an X-ray or CT scan of the skull. Additional images [ edit ] Hyperostosis frontalis at CT References [ edit ] She R, Szakacs J (2004). "Hyperostosis frontalis interna: case report and review of literature".

In addition to thickening of the inner table of the frontal bone, obesity and hypertrichosis may be present. This condition affects mainly females. Knies and Le Fever (1941) reported mother and 3 children affected. Thus, the disorder may be dominant, but whether autosomal or X-linked is not known. Lieberman (1967) has observed 5 affected females in 3 generations. No case of male-to-male transmission is known. Rosatti (1972) described a family with 12 affected members (10 of them females) in 4 successive generations.

A rare hereditary demyelinating motor and sensory neuropathy characterized by slowed nerve conduction velocities, in the absence of clinically apparent neurological deficits, gait abnormalities or muscular atrophy, associated with a germline mutation in the ARGHEF10 gene.

A number sign (#) is used with this entry because of evidence that distal hereditary motor neuropathy type IIC (HMN2C) is caused by heterozygous mutation in the HSPB3 gene (604624) on chromosome 5q11. One such family has been reported. For a general phenotypic description and a discussion of genetic heterogeneity of distal HMN (dHMN), see HMN type I (HMN1; 182960). Clinical Features Kolb et al. (2010) reported 2 sisters with adult-onset distal hereditary motor neuropathy. The proband was a 58-year-old woman who presented with a history of slowly progressive distal arm and leg weakness. Her symptoms began in her early twenties, when she noticed easy fatigability in her legs, frequent ankle turning, and instability going up and down stairs.

A number sign (#) is used with this entry because of evidence that distal hereditary motor neuronopathy type IID (HMN2D) is caused by heterozygous mutation in the FBXO38 gene (608533) on chromosome 5q32. Description Distal hereditary motor neuronopathy type IID is an autosomal dominant neurologic disorder characterized by onset of slowly progressive distal lower limb weakness and atrophy between the second and fourth decades of life. Weakness usually begins in the calf muscles and later involves more proximal muscles. The severity is variable, and some patients have difficulty walking or running. Most also have upper limb involvement, particularly of the triceps and intrinsic hand muscles.

A number sign (#) is used with this entry because distal hereditary motor neuronopathy type 2B (dHMN2B or HMN2B) is caused by heterozygous mutation in the gene encoding heat-shock 27-kD protein-1 (HSPB1; 602195) on chromosome 7q11. Axonal Charcot-Marie-Tooth disease type 2F (CMT2F; 606595) is an allelic disorder with a similar phenotype. For a general phenotypic description and a discussion of genetic heterogeneity of distal HMN (dHMN), see HMN type I (HMN1; 182960). Clinical Features Houlden et al. (2008) reported 5 families with HMN2B. All patients had a remarkably similar slowly progressive disease course with a mean age at onset ranging from 21 to 54 years.

A number sign (#) is used with this entry because distal hereditary motor neuronopathy type IIA (dHMN2A or HMN2A) is caused by heterozygous mutation in the gene encoding heat-shock 22-kD protein-8 (HSPB8; 608014) on chromosome 12q24. Charcot-Marie-Tooth disease type 2L (CMT2L; 608673) is an allelic disorder with an overlapping phenotype. For a general phenotypic description and a discussion of genetic heterogeneity of distal HMN, see HMN type I (HMN1; 182960). Clinical Features Nelson and Amick (1966) reported a family in which 6 members had insidious onset and gradual progression of symmetrical distal atrophy and weakness of the extremities associated with hyporeflexia. Age at onset ranged from 20 to 40 years and the inheritance appeared to be autosomal dominant.

A rare, genetic, neuromuscular disease characterized by progressive, symmetrical, moderate to severe, distal muscle weakness and atrophy, without sensory involvement, first affecting the lower limbs (towards the end of the first decade) and then involving (within two years) the upper extremities. Patients typically develop foot drop, pes varus, hammer toes and claw hands. Pyramidal tract signs (such as brisk knee reflexes and positive Babinski sign) with absent ankle reflexes are initially associated but regress as disease stabilizes (~10 years after onset).

A number sign (#) is used with this entry because of evidence that autosomal recessive distal spinal muscular atrophy-2 (DSMA2) is caused by homozygous mutation in the SIGMAR1 gene (601978) on chromosome 9p13. One such family has been reported. Description Distal spinal muscular atrophy-2 is an autosomal recessive neuromuscular disorder characterized by onset of distal muscle weakness and wasting affecting the lower and upper limbs in the first decade; there is no sensory involvement (summary by Li et al., 2015). For a general phenotypic description and a discussion of genetic heterogeneity of DSMA, see HMN1 (182960). Clinical Features Christodoulou et al. (2000) identified a novel form of autosomal recessive distal hereditary motor neuropathy in 27 patients belonging to a cluster of 7 consanguineous families from neighboring villages of the Jerash region of Jordan. Onset of the disease occurred between ages 6 and 10 years and was characterized by weakness and atrophy of the lower limbs associated with pyramidal features.

A number sign (#) is used with this entry because of evidence that mitochondrial DNA depletion syndrome-4B (MTDPS4B), which manifests as a neurogastrointestinal encephalopathy (MNGIE), is caused by compound heterozygous mutation in the POLG gene (174763) on chromosome 15q26. See also MTDPS1 (603041) for a more common form of MNGIE caused by recessive mutation in the thymidine phosphorylase gene (TYMP; 131222). Description Mitochondrial DNA depletion syndrome-4B is an autosomal recessive progressive multisystem disorder clinically characterized by chronic gastrointestinal dysmotility and pseudoobstruction, cachexia, progressive external ophthalmoplegia (PEO), axonal sensory ataxic neuropathy, and muscle weakness (van Goethem et al., 2003). For a discussion of genetic heterogeneity of autosomal recessive mtDNA depletion syndromes, see MTDPS1 (603041). Clinical Features Vissing et al. (2002) reported 2 sisters who presented at age 15 years with unsteady gait and gastrointestinal malabsorption.

Diagnosis Suggestive Findings MNGIE ( m itochondrial n euro g astro i ntestinal e ncephalopathy) disease is suggested by the presence of the following clinical findings, neuroimaging, and family history [Hirano et al 1994, Nishino et al 1999, Garone et al 2011]: Clinical findings Severe gastrointestinal (GI) dysmotility Cachexia Ptosis External ophthalmoplegia Sensorimotor neuropathy (usually mixed axonal and demyelinating) Neuroimaging. ... Parental consanguinity is common, occurring in nearly half the families in some reports [Nishino et al 1999, Nishino et al 2000]. Differential Diagnosis MNGIE ( m itochondrial n euro g astro i ntestinal e ncephalopathy) disease has been confused with anorexia nervosa and other classes of GI diseases such as intestinal pseudo-obstruction (e.g., ACTG2 -related disorders), inflammatory bowel disease, celiac disease, and irritable bowel disease. ... Management Evaluations at Initial Diagnosis To establish the extent of disease and needs in a proband with MNGIE ( m itochondrial n euro g astro i ntestinal e ncephalopathy) disease, the following are recommended: EMG/NCV Brain MRI EKG Ophthalmologic evaluation Audiologic evaluation Assessment of hepatic function, renal function, plasma concentrations of amino acids, and serum concentration of lactate and pyruvate GI evaluation, which depends on the symptoms and may include abdominal films, abdominal CT, upper GI contrast radiography, esophagogastroduodenoscopy, sigmoidoscopy, liquid phase scintigraphy, and antroduodenal manometry.

A number sign (#) is used with this entry because mitochondrial DNA depletion syndromes 8A (MTDPS8A) and 8B (MTDPS8B) are caused by homozygous or compound heterozygous mutation in the RRM2B gene (604712) on chromosome 8q22. See also PEOA5 (613077), an allelic disorder caused by heterozygous mutations in the RRM2B gene. Description Mitochondrial DNA depletion syndrome-8A is a severe autosomal recessive disorder characterized by neonatal hypotonia, lactic acidosis, and neurologic deterioration. Renal tubular involvement may also occur (Bourdon et al., 2007). Mitochondrial DNA depletion syndrome-8B is characterized by ophthalmoplegia, ptosis, gastrointestinal dysmotility, cachexia, peripheral neuropathy, and brain MRI changes, known as the MNGIE phenotype (Shaibani et al., 2009). For a discussion of genetic heterogeneity of mtDNA depletion syndromes, see MTDPS1 (603041).

Retrieved 2015-12-03 . ^ a b c d e f g h i j k l m n o p q r s t u Garone, Caterina; Tadesse, Saba; Hirano, Michio (2011-11-01).

Mitochondrial neurogastrointestinal encephalopathy (MNGIE) syndrome is a condition that mainly affects the digestive system and nervous system. Signs and symptoms most often begin by age 20 and worsen with time. Almost all people with MNGIE have gastrointestinal dysmotility, in which the muscles and nerves of the digestive system do not move food through the digestive tract efficiently and result in early satiety, nausea, dysphagia, gastroesophageal reflux, vomiting after eating (postprandial emesis), episodic abdominal pain and/or distention, and diarrhea . Affected people may also have cachexia, dropped eyelids or weakness of other muscles of the eyes, peripheral neuropathy (manifesting as tingling, numbness, and pain (paresthesias) symmetric weakness, that mainly affect the lower extremities) and hearing loss. Leukoencephalopathy, which is the deterioration of a type of brain tissue known as white matter, is a hallmark of MNGIE; however it does not usually cause symptoms in people with this disorder. MNGIE is caused by variations (mutations) in the TYMP gene, important for allowing adequate levels of thymidine in the mitochondria.

A number sign (#) is used with this entry because mitochondrial DNA depletion syndrome-1 (MTDPS1), which manifests as a neurogastrointestinal encephalopathy (MNGIE), is caused by homozygous or compound heterozygous mutation in the nuclear-encoded thymidine phosphorylase gene (TYMP; 131222) on chromosome 22q13. See also MTDPS4B (613662) for a less common form of MNGIE caused by recessive mutation in the DNA polymerase gamma gene (POLG; 174763). Description Mitochondrial DNA depletion syndrome-1 (MTDPS1) is an autosomal recessive progressive multisystem disorder clinically characterized by onset between the second and fifth decades of life of ptosis, progressive external ophthalmoplegia (PEO), gastrointestinal dysmotility (often pseudoobstruction), cachexia, diffuse leukoencephalopathy, peripheral neuropathy, and mitochondrial dysfunction. Mitochondrial DNA abnormalities can include depletion, deletion, and point mutations (Taanman et al., 2009). Genetic Heterogeneity of Mitochondrial DNA Depletion Syndromes Mitochondrial DNA depletion syndromes are clinically and genetically heterogeneous, and most are autosomal recessive disorders.

J Surg Oncol . 95 (6): 519–22. doi : 10.1002/jso.20730 . PMID 17192915 . ^ Hisaoka M, Ishida T, Kuo TT, et al. (March 2008).

A rare soft tissue tumor characterized by a slowly growing mass typically involving tendons and aponeuroses of the extremities, composed of polygonal or spindle-shaped cells with melanocytic differentiation. The tumor typically affects young adults, who often present with pain or tenderness at the tumor site. Prognosis is poor with high recurrence rates and frequent metastasis, especially to lymph nodes, lung, and bones.

Alternating hemiplegia of childhood is a neurological condition characterized by recurrent episodes of temporary paralysis, often affecting one side of the body (hemiplegia). During some episodes, the paralysis alternates from one side of the body to the other or affects both sides at the same time. These episodes begin in infancy or early childhood, usually before 18 months of age, and the paralysis lasts from minutes to days. In addition to paralysis, affected individuals can have sudden attacks of uncontrollable muscle activity; these can cause involuntary limb movements (choreoathetosis), muscle tensing (dystonia), movement of the eyes (nystagmus), or shortness of breath (dyspnea). People with alternating hemiplegia of childhood may also experience sudden redness and warmth (flushing) or unusual paleness (pallor) of the skin.

Overview Dyshidrosis is a skin condition that causes small, fluid-filled blisters to form on the palms of the hands and sides of the fingers. Sometimes the bottoms of the feet are affected too. The itchy blisters last a few weeks and often come back. Treatment for dyshidrosis most often includes prescription steroid skin creams or ointments. Your doctor or other health care provider may suggest a different treatment, such as light therapy or medicine taken by mouth or injection. The right treatment depends on how severe your symptoms are. Dyshidrosis is also called dyshidrotic eczema and pompholyx.