TaoMedAI/RareMedData huggingface dataset:
Mesomelic dysplasia, Kantaputra type (ORPHA:1836)
Mesomelic dysplasia Kantaputra type (MDK) is a rare skeletal disease characterized by symmetric shortening of the middle segments of limbs and short stature.
Epidemiology
It has been described in five families.
Clinical description
In the upper limbs, the ulnae are very short, and the radii are bowed. The distal humerus has a dumbbell shape. The hands show progressive flexion contractures of the proximal interphalangeal joints. In the lower limbs, feet are fixed in plantar flexion so that the patients walk on their toetips. The prominent distal fibula on the ventral aspect is common and considered a hallmark. Fibula, talus and calcaneus are small and fibulo-calcaneal synostosis is a characteristic feature. Carpal and tarsal synostoses are observed in some individuals. All affected patients have normal craniofacial features and intelligence.
Etiology
Using microarray-based comparative genomic hybridization (array-CGH), two microduplications have been identified on chromosome 2 (2q31.1-q31.2), separated by a segment of normal copy number. The more centromeric duplication encompasses the HOXD cluster and it is proposed that duplications cause dysregulation of HOXD gene expression.
Genetic counseling
In all families, the condition is transmitted as an autosomal dominant trait.

                            Last update: 
                            November 2010
Mesomelic dysplasia, Nievergelt type (ORPHA:2633)
A rare primary bone dysplasia characterized by severe mesomelic shortness particularly of the lower limbs with distinctive triangular or rhomboid-shaped tibiae and fibulae, accompanied by bony protuberances and skin dimples. Additional manifestations include radioulnar synostosis, dislocation of the radial head, abnormalities of the hands (such as oligosyndactyly or fusiform-shaped fingers) and feet (pes equinovarus, synostoses of tarsals/metatarsals and phalanges), and dysmorphic facial features.
Mesomelic dysplasia, Savarirayan type (ORPHA:85170)
Mesomelic dysplasia, Savarirayan type is characterised by severely hypoplastic and triangular-shaped tibiae, and absence of the fibulae. So far, two sporadic cases have been described. Moderate mesomelia of the upper limbs, proximal widening of the ulnas, pelvic anomalies and marked bilateral glenoid hypoplasia were also reported.
Metabolic myopathy due to lactate transporter defect (ORPHA:171690)
Metabolic myopathy due to lactate transporter defect is a rare metabolic myopathy characterized by muscle cramping and/or stiffness after exercise (especially during heat exposure), post-exertional rhabdomyolysis and myoglobinuria, and elevation of serum creatine kinase.
Metachondromatosis (ORPHA:2499)
Metachondromatosis (MC) is a rare disorder characterized by the presence of both multiple enchondromas and osteochondroma-like lesions.
Epidemiology
The prevalence is unknown and fewer than 40 cases have been reported.
Clinical description
The first signs of MC occur during the first decade of life. Most frequently, osteochondromas occur in the hands and feet, predominantly in digits and toes, and enchondromas involve the iliac crests and metaphyses of long bones. Osteochondromas are small and point towards the adjacent growth plate. MC does not lead to shortening or bowing of the long bones, joint deformity, or subluxation. The lesions spontaneously decrease in size or regress.
Etiology
Loss-of-function mutations, including deletions, non-sense mutations and splice sites mutations, of the PTPN11 gene (12q24) have been linked to MC in several families.
Diagnostic methods
Diagnosis is based on clinical signs, radiographic findings and familial history. The radiographic features are osteochondromas at the metaphyses of the short tubular bones (hands and feet) pointing towards the joints and coexisting with enchondromas.
Differential diagnosis
The differential diagnosis should include hereditary multiple osteochondromas (MO; see this term) in which the long bones are predominantly affected and the lesions point away from the joint/growth plate and may result in shortening or deformity of the affected bones. Other diseases to be considered include the non-hereditary conditions Ollier disease and Maffucci syndrome (in which multiple enchondromas are found in the medulla of the bone and are predominantly unilateral), and dysplasia epiphysealis hemimelica (DEH; characterized by a cartilaginous overgrowth mainly located in the lower extremities on one side of the body) (see these terms).
Antenatal diagnosis
Antenatal diagnosis is technically feasible.
Genetic counseling
MC has an autosomal dominant mode of inheritance. Genetic counseling may be proposed to the patients and their families.
Management and treatment
For severe malalignment of the fingers/toes, surgical intervention can be considered to remove osteochondromas.
Prognosis
No malignant transformation has been reported so far. Clinical course is unpredictable as there may be simultaneous growth of some of the lesions and regression of others. Nerve paralysis or vascular complications (avascular necrosis of the femoral head; see this term) may occur.

                            Last update: 
                            May 2011


                            - Expert reviewer(s): 
                            Pr J.V.M.G. [Judith] BOVÉE  -  Christianne REIJNDERS
Metachromatic leukodystrophy, adult form (ORPHA:309271)
A subtype of Metachromatic leukodystrophy characterized by progressive psychomotor regression with an insidious onset after the age of 16 years, most often beginning with intellectual and behavioral changes, such as memory deficits or emotional instability. The clinical picture is dominated by gradual cognitive, later also motor, decline, taking a protracted course with periods of waxing and waning. Decerebration and death occur within decades after disease onset.
Metachromatic leukodystrophy, juvenile form (ORPHA:309263)
A subtype of Metachromatic leukodystrophy characterized by progressive psychomotor regression with an onset between 30 months and 16 years of age, often beginning with behavioral abnormalities or deterioration of school performance. Further manifestations are ataxia, gait disturbances, reduced deep tendon reflexes, spasticity, seizures, paralysis, dementia, and loss of speech, vision, and hearing, eventually resulting in complete loss of motor and cognitive skills, and decerebration. The rate of deterioration is variable with possible survival up to the third decade of life.
Metachromatic leukodystrophy, late infantile form (ORPHA:309256)
A subtype of Metachromatic leukodystrophy characterized by rapidly progressive psychomotor regression with an onset before 30 months of age after a period of apparently normal development. Manifestations developing during the course of the disease are impaired feeding and swallowing due to pseudobulbar palsies, seizures, painful spasms, muscle weakness, ataxia, paralysis, dementia, and loss of speech, vision, and hearing, quickly resulting in complete loss of motor and cognitive skills, and decerebration. Death occurs within the first decade of life.
Metachromatic leukodystrophy (ORPHA:512)
A rare lysosomal disease characterized by accumulation of sulfatides in the central and peripheral nervous system due to deficiency of the enzyme arylsulfatase A, leading to demyelination. Three clinical subtypes can be distinguished based on the age of onset: late infantile, juvenile, and adult. Lead symptoms are deterioration in motor or cognitive function or behavioral problems, depending on the subtype, all eventually culminating in a decerebrated state and death after a highly variable disease course and duration. Mode of inheritance is autosomal recessive.
Metaphyseal anadysplasia (ORPHA:1040)
A rare form of metaphyseal dysplasia characterized by short stature, rhizomelic micromelia and a mild varus deformity of the legs evident from the first months of life, that is associated with radiological features of severe metaphyseal changes (irregularities, widening and marginal blurring) in long bones, most prominent in proximal femurs, and generalized osteopenia, and that usually spontaneously resolves by the age of three years. Severe autosomal dominant and milder recessive variants have been observed.
Metaphyseal chondrodysplasia, Jansen type (ORPHA:33067)
A rare autosomal dominant skeletal dysplasia characterized by short-limbed short stature (due to severe metaphyseal changes that are often discovered in childhood by imaging), waddling gait, bowed legs, contracture deformities of the joints, short hands with clubbed fingers, clinodactyly, prominent upper face and small mandible, as well as chronic parathyroid hormone-independent hypercalcemia, hypercalciuria, and mild hypophosphatemia.
Metaphyseal chondrodysplasia, Kaitila type (ORPHA:166038)
Metaphyseal chondrodysplasia, Kaitila type is a rare multiple metaphyseal dysplasia disease characterized by disproportionate short stature, short limbs and digits, tracheobronchial malacia and progressive thoracolumbar scoliosis. Radiographic imaging shows progression from marked metaphyseal dysplasia of tubular bones in childhood to short and broad bones with mild dysplasia of the joints in adulthood. There have been no further descriptions in the literature since 1982.
Metaphyseal chondrodysplasia, Rosenberg type (ORPHA:1837)
Ulna metaphyseal dysplasia syndrome is a rare primary bone dysplasia characterized by dysplasia of the distal ulnar metaphyses, as well as metacarpal/metatarsal dysplasia and metaphyseal changes resembling enchondromata. Patients usually present bony swelling of the wrists with or without pain (knees and ankles may also be affected). Other variably associated features include platyspondyly, skeletal development delay, short stature and coxa valga.
Metaphyseal chondrodysplasia, Schmid type (ORPHA:174)
Schmid metaphyseal chondrodysplasia is a rare disorder characterized by moderately short stature with short limbs, coxa vara, bowlegs and an abnormal gait.
Epidemiology
Prevalence is unknown.
Etiology
The disorder is caused by mutations in the COL10A1 (6q21-q22) gene encoding the collagen alpha-1(X) chain.
Diagnostic methods
The condition is usually diagnosed during the second or third year of life. Diagnosis relies on detection of the metaphyseal lesions at radiography.
Differential diagnosis
Hypochondroplasia (see this term) and sequelae from rickets are the principle differential diagnoses. Other metaphyseal dysplasias (such as cartilage-hair hypoplasia or Jansen type metaphyseal chondrodysplasia; see these terms) can be excluded as they are associated with very short stature and other features.
Antenatal diagnosis
Prenatal diagnosis should not be proposed for this disease.
Genetic counseling
Schmid metaphyseal chondrodysplasia is transmitted in an autosomal dominant manner. Genetic counseling may be recommended with a 50% risk of recurrence.
Management and treatment
Orthopedic correction is the only possible treatment.

                            Last update: 
                            November 2008


                            - Expert reviewer(s): 
                            Dr Martine LE MERRER
Metaphyseal chondrodysplasia, Spahr type (ORPHA:2501)
A rare, genetic, primary bone dysplasia disease characterized by usually moderate, postnatal short stature, progressive genu vara deformity, a waddling gait, and radiological signs of metaphyseal dysplasia (i.e. irregular, sclerotic and widened metaphyses), in the absence of biochemical abnormalities suggestive of rickets disease. Intermittent knee pain, lordosis, and delayed motor development may also occasionally be associated.
Metaphyseal chondromatosis with D-2-hydroxyglutaric aciduria (ORPHA:99646)
Metaphyseal chondromatosis with D-2-hydroxyglutaric aciduria is an extremely rare genetic disorder characterized by the unique association of enchondromatosis with D-2 hydroxyglutaric aciduria (see these terms). Clinical features include enchondromatosis (with short stature, severe metaphyseal dysplasia and mild vertebral involvement), elevated levels of urinary 2-hydroxyglutaric acid and mild developmental delay.
Metaphyseal dysostosis-intellectual disability-conductive deafness syndrome (ORPHA:2502)
Metaphyseal dysostosis-intellectual disability-conductive deafness syndrome is characterised by metaphyseal dysplasia, short-limb dwarfism, mild intellectual deficit and conductive hearing loss, associated with repeated episodes of otitis media in childhood. It has been described in three brothers born to consanguineous Sicilian parents. Variable manifestations included hyperopia and strabismus. The mode of inheritance is autosomal recessive.
Metaphyseal dysplasia, Braun-Tinschert type (ORPHA:85188)
Metaphyseal dysplasia, Braun-Tinschert type is characterised by metapyhseal undermodeling with broadening of the long bones and femora with an 'Erlenmeyer flask'' appearance, expansion and bowing of the radii with severe varus deformity and flat exostoses of the long bones at the metadiaphyseal junctions.
Epidemiology
It has been described in four German families originating from the same town in Bohemia and in a 7-year-old Japanese girl.
Differential diagnosis
Erlenmeyer flask deformity is also a prominent feature of the autosomal recessive Pyle type of metaphyseal dysplasia (see this term). The two conditions can be distinguished by the mode of inheritance and by the presence of the marked varus deformity of the distal part of the radii in Braun-Tinschert metaphyseal dysplasia.
Genetic counseling
Transmission of metaphyseal dysplasia, Braun-Tinschert type is autosomal dominant.

                            Last update: 
                            June 2007
Metaphyseal dysplasia-maxillary hypoplasia-brachydacty syndrome (ORPHA:2504)
Metaphyseal dysplasia-maxillary hypoplasia-brachydacty syndrome is characterized by metaphyseal dysplasia associated with short stature and facial dysmorphism (a beaked nose, short philtrum, thin lips, maxillary hypoplasia, dystrophic yellowish teeth) and acral anomalies (short fifth metacarpals and/or short middle phalanges of fingers two and five). It has been described in several members spanning four generations of a French-Canadian family. The syndrome is likely to be transmitted as an autosomal dominant trait.
Metaplastic carcinoma of the breast (ORPHA:213531)
Metaplastic carcinoma of the breast is a rare, aggressive subtype of invasive breast carcinoma characterized by rapid growth, relatively large tumor size and a tendency to metastasize to distant organs, particularly the lungs, with relatively less frequent involvement of the axillary lymph nodes. Histologically, the tumor shows high-grade cellularity and heterologous differentiation, including chondroid, osseous, pleomorphic/sarcomatoid, spindled, and squamous elements. Patients usually present with a fast-growing, large, well-circumscribed, mobile lump in the breast, which can become painful and involve the chest wall and the skin, leading to ulceration.
Methanol poisoning (ORPHA:31825)
Methanol poisoning is a rare poisoning resulting in elevated anion gap metabolic acidosis, due to the alcohol dehydrogenase (ADH)-mediated production of formic acid (which is poisonous to the central nervous system), and characterized by dizziness, nausea, vomiting, confusion, metabolic acidosis, visual disturbances (which if left untreated can lead to blindness), coma, and death (due to respiratory failure).
Methimazole embryofetopathy (ORPHA:1923)
A teratogenic embryofetopathy that results from maternal exposition to methimazole (MMI; or the parent compound carbimazole) in the first trimester of pregnancy. MMI is an antithyroid thionamide drug used for the treatment of Graves' disease. In the infant, MMI may result in choanal atresia, esophageal atresia, omphalocele, omphalomesenteric duct anomalies, congenital heart disease (such as ventricular septal defect), renal system malformations and aplasia cutis. Additional features that may be observed include facial dysmorphism (short upslanting palpebral fissures, a broad nasal bridge with a small nose and a broad forehead) and athelia/hypothelia.
Methionine adenosyltransferase I/III deficiency (ORPHA:168598)
A rare inborn error of metabolism characterized by persistently elevated serum methionine levels. Half of patients reported with MAT I/III deficiency, notably those with hypermethioninemia below 800 µM, have no CNS abnormalities and are clinically asymptomatic. However, individuals with higher levels might show evidence of central nervous system abnormalities, most notably hypo- or demyelination on brain MRI, as well as developmental delay and intellectual disability. Bad breath or a strong smell of urine and sweat may be noted in some patients.
Methotrexate toxicity (ORPHA:565782)
A rare intoxication characterized by acute renal tubular toxicity due to crystallization of methotrexate in the renal tubular lumen (which in turn leads to impaired methotrexate clearance and further deterioration of renal function and exacerbation of non-renal adverse events), myelosuppression with pancytopenia, gastrointestinal mucositis, maculopapular skin rash, chemical conjunctivitis, hepatotoxicity (reversible chemical hepatitis and hyperbilirubinemia), pulmonary toxicity, and, in severe cases, multiorgan failure. Central nervous system involvement, including headaches, seizures, and stroke-like symptoms, may also be observed.
Methotrexate-associated lymphoproliferative disorders (ORPHA:86904)
Methotrexate-associated lymphoproliferative disorders are rare immunodeficiency-associated lymphoproliferative diseases characterized by lymphoid proliferation or lymphomas (large B-cell lymphoma, T-cell lymphoma, Hodgkin lymphoma, reactive lymphadenitis and a polymorphic post-transplant lymphoproliferative disorder) that develop in patients with different autoimmune diseases treated with methotrexate. Swelling is the predominant manifestation of the disease and regression after methotrexate withdrawal is observed in a significant proportion of patients.
Methylmalonic acidemia due to methylmalonyl-CoA epimerase deficiency (ORPHA:308425)
Methylmalonic acidemia due to methylmalonyl-CoA epimerase deficiency is a rare inborn error of metabolism disease characterized by mild to moderate, persistent elevation of methylmalonic acid in plasma, urine and cerebrospinal fluid. Clinical presentation may include acute metabolic decompensation with metabolic acidosis (presenting with vomiting, dehydration, confusion, hallucinations), nonspecific neurological symptoms, or may also be asymptomatic.
Methylmalonic acidemia with homocystinuria type cblF (ORPHA:79284)
cblF type methylmalonic acidemia with homocystinuria is a form of methylmalonic acidemia with homocystinuria (see this term), an inborn error of vitamin B12 (cobalamin) metabolism characterized by megaloblastic anemia, lethargy, failure to thrive, developmental delay, intellectual deficit and seizures.
Epidemiology
To date, 15 cases have been reported.
Clinical description
cblF type methylmalonic acidemia with homocystinuria has a variable age of onset (from birth to 11 years of age) and manifestations also vary and can include development delay, feeding difficulties, signs of megaloblastic anemia (pallor, fatigue, anorexia), hypotonia, stomatitis and skin rashes.
Etiology
The disorder is caused by mutations in the LMBRD1 gene (6q13) and is transmitted in an autosomal recessive manner.

                            Last update: 
                            March 2012


                            - Expert reviewer(s): 
                            Dr David ROSENBLATT  - Dr David WATKINS
Methylmalonic acidemia with homocystinuria, type cblC (ORPHA:79282)
cblC type methylmalonic acidemia with homocystinuria is a form of methylmalonic acidemia with homocystinuria (see this term), an inborn error of vitamin B12 (cobalamin) metabolism characterized by megaloblastic anemia, lethargy, failure to thrive, developmental delay, intellectual deficit and seizures.
Epidemiology
To date, over 500 cases of cblC have been reported, making it the most frequent type of methylmalonic acidemia with homocystinuria.
Clinical description
The disease typically presents with failure to thrive, acute neurological deterioration, intellectual deficit, lethargy, seizures, microcephaly, a salt-and-pepper retinopathy, and signs of megaloblastic anemia (pallor, fatigue, anorexia). Severe brain abnormalities including hydrocephalus, white matter abnormalities, cerebral atrophy, and unusual basal ganglia lesions are common. Onset of the disorder can be early (infantile) or late (juvenile or adult), with the late-onset form characterized by ataxia, dementia and psychosis.
Etiology
cblC type methylmalonic acidemia with homocystinuria is caused by mutations in the MMACHC gene (1p36.3) and is transmitted in an autosomal recessive manner.

                            Last update: 
                            March 2012


                            - Expert reviewer(s): 
                            Dr David ROSENBLATT  - Dr David WATKINS
Methylmalonic acidemia with homocystinuria, type cblD (ORPHA:79283)
cblD type methylmalonic acidemia with homocystinuria is a form of methylmalonic acidemia with homocystinuria (see this term), an inborn error of vitamin B12 (cobalamin) metabolism characterized by variable biochemical, neurological and hematological manifestations.
Epidemiology
To date, 17 cases of cblD have been reported (6 classic cblD, 5 cblDv1 and 6 cblDv2).
Clinical description
Three different presentations have been described: the classic form with combined methylmalonic aciduria and homocystinuria; cblD variant 1 (cblDv1) with isolated homocystinuria; and cblD variant 2 (cblDv2) with isolated methylmalonic aciduria. Clinical presentation is extremely variable. The disorder can present from early infancy to late childhood. Presenting signs are variable depending on which aspect(s) of cobalamin metabolism are affected and can include developmental delay, severe learning difficulties, seizures, movement and gait abnormalities, behavioral problems and signs of megaloblastic anemia (pallor, fatigue, anorexia).
Etiology
The causal gene for cblD is MMADHC (2q23.2) and the disorder is transmitted in an autosomal recessive manner.

                            Last update: 
                            March 2012


                            - Expert reviewer(s): 
                            Dr David ROSENBLATT  - Dr David WATKINS