TaoMedAI/RareMedData huggingface dataset:
Distal myopathy with posterior leg and anterior hand involvement (ORPHA:63273)
Distal myopathy with posterior leg and anterior hand involvement, also named distal ABD-filaminopathy, is a neuromuscular disease characterized by a progressive symmetric muscle weakness of anterior upper and posterior lower limbs.
Epidemiology
It has been described in several members of an Australian and an Italian family.
Clinical description
The disease usually manifests during the third decade of life with thenar muscle weakness resulting in reduced grip strength. The disease is slowly progressive and generally proceeds with calf muscle weakness appearing during the fourth decade and proximal muscles becoming perceptibly affected in the fifth decade. The tibial anterior muscle is spared, so is respiratory function. Mild cardiomyopathy can sometimes be observed.
Etiology
The disease is due to mutations on the actin-binding domain of the FLNC gene that encodes filamin C, a muscle specific filamin that is also associated with myofibrillar myopathy when mutations affect other parts of the protein. The disease mechanism seems to be linked to an increased actin-binding affinity of filamin C.
Genetic counseling
Transmission is autosomal dominant.

                            Last update: 
                            April 2012


                            - Expert reviewer(s): 
                            Dr Rachael DUFF
Distal myopathy, Tateyama type (ORPHA:488650)
Distal myopathy, Tateyama type is a rare, genetic, slowly progressive, distal myopathy disorder characterized by muscle atrophy and weakness limited to the small muscles of the hands and feet (in particular, thenar and hypothenar muscle atrophy), increased serum creatine kinase, and severely reduced caveolin-3 expression on muscle biopsy. Some patients may also show calf hypertrophy, pes cavus, and signs of muscle hyperexcitability.
Distal myopathy (ORPHA:599)
Distal myopathy refers to a group of muscle diseases which share the clinical pattern of predominant weakness and atrophy beginning in the feet and/or hands.
Epidemiology
The estimated prevalence of distal myopathy in the northern region of England is 1/300,000. Some forms have been identified with greater frequency in certain populations. For example, tibial muscular dystrophy is frequent in Finland with a prevalence of 1/5,000 and Welander distal myopathy occurs with greater frequency in Sweden.
Clinical description
Distal myopathy is characterized by progressive muscular weakness and atrophy beginning in the distal parts of upper and lower limbs with an extremely variable age of onset. Distal myopathy is a genetically heterogeneous group (currently comprising more than 20 genetic types) which affects different regions of the distal extremities and is classified according to clinical features, inheritance pattern, histopathological criteria, and molecular genetics. The main autosomal dominant forms of distal myopathy are Welander distal myopathy (weakness in the distal upper extremities which later progresses to distal lower extremity), tibial muscular dystrophy (mainly affects the front of the lower leg), distal myotilinopathy (progressive distal muscle weakness and peripheral neuropathy with hyporeflexia), late-onset distal myopathy, Markesbery-Griggs type (ZASP-related myofibrillar myopathy), Laing early-onset distal myopathy, distal myopathy with posterior leg and anterior hand involvement (distal ABD-filaminopathy), and adult-onset distal myopathy due to VCP mutation. The genetically confirmed autosomal recessive forms are distal myopathy, Nonaka type (GNE-myopathy, weakness in the anterior distal legs), Miyoshi myopathy (weakness in the distal lower extremity posterior compartment), nebulin-related early-onset distal myopathy and distal anoctaminopathy. The age at onset is extremely variable and for recessive varieties of distal myopathy, symptoms usually develop in early adult life whereas in the dominant Welander and tibial muscular dystrophy, the onset is usually later. However, in some disorders (i.e. Laing early-onset distal myopathy and nebulin-related early-onset distal myopathy) the onset may be during childhood, and even in infancy.
Etiology
Distal myopathy is caused by defect or lack of specific proteins that play an essential role in the proper function and health of muscle cells. 15 causative genes have to date been associated with distal myopathy: ANO5 (11p15.1), CRYAB (11q22.3-q23.1), DES (2q35), DYSF (2p13.3), FLNC (7q32-q35), GNE (9p13.1), KLHL9 (9p22), LDB3 (10q22.3-q23.2), MATR3 (5q31.3), MYH7 (14q11.2-q13),  MYOT (5q31.2),  NEB (2q22), TIA1 (2p13), TTN (2q31) and VCP (9p13.3).
Genetic counseling
Distal myopathy can be inherited as an autosomal dominant or as an autosomal recessive trait.

                            Last update: 
                            June 2015


                            - Expert reviewer(s): 
                            Dr Johanna PALMIO  - Pr Bjarne UDD
Distal myotilinopathy (ORPHA:98911)
A rare, late adult-onset myofibrillar myopathy characterized by progressive distal muscle weakness associated with peripheral neuropathy and hyporeflexia. Ambulation may be lost within a few years.
Distal nebulin myopathy (ORPHA:399103)
Distal nebulin myopathy is a rare, slowly progressive, autosomal recessive distal myopathy characterized by early onset of predominantly distal muscle weakness and atrophy affecting lower leg extensor muscles, finger extensors and neck flexors. Muscle histology does not always show nemaline rods.
Epidemiology
To date, the disease has been described in 13 patients from five unrelated Finnish families and four non-Finnish families.
Clinical description
Distal nebulin myopathy manifests initially, in early childhood or young adulthood, by foot drop, but the first symptoms can be seen as early as one year of age. The most severely affected muscles include the ankle dorsiflexors, the finger extensors and the neck flexors. Patients are usually not able to walk on their heels and later in the disease course, there is a mild proximal muscle involvement. Additional features include early-onset moderate facial weakness and mild respiratory problems, such as shortness of breath on strenuous exercise (although only one patient presenting decreased vital capacity has been reported). Cardiac muscle is usually not affected, however cardiomyopathy has been described in one patient.
Etiology
Distal nebulin myopathy is caused by biallelic mutations (with at least one of them being missense mutation) in the gene NEB (2q22) which encodes the protein nebulin. The latter is expressed in the thin filaments of striated muscle and is required for the proper assembly of the thin filaments, for the maintenance of their lengths and for their contractile function.
Diagnostic methods
Diagnosis is based on clinical, muscle histology and laboratory examinations. Muscle histology shows a marked fiber size variation, presence of hypertrophic fibers with internal nuclei, and variably abundant nemaline rods. CK levels are normal or slightly increased. Diagnosis is confirmed by genetic screening of NEB.
Differential diagnosis
Differential diagnosis includes other distal myopathies, especially Laing distal myopathy.
Genetic counseling
Transmission is autosomal recessive and genetic counseling is recommended for at-risk couples (both individuals are carriers of a disease-causing mutation) informing them of the 25% risk of having an affected child.
Management and treatment
Currently no specific treatment is available. Management is mainly symptomatic and includes the help of an occupational and a physical therapists. Foot drop may be aided by orthoses. Occasional monitoring of respiratory function is recommended.
Prognosis
Prognosis is good with patients typically remaining ambulant although proximal weakness may occur at the later stages.

                            Last update: 
                            September 2018


                            - Expert reviewer(s): 
                            Dr Johanna PALMIO  - Pr Bjarne UDD
Distal renal tubular acidosis with anemia (ORPHA:93610)
A rare form of distal renal tubular acidosis characterized by a defect in renal acidification and hereditary hemolytic anemia.
Distal spinal muscular atrophy type 3 (ORPHA:139547)
Distal spinal muscular atrophy type 3 is a rare neuromuscular disease characterized by progressive muscular weakness and atrophy predominantly affecting distal parts of limbs, later involvement of proximal and trunk muscles with marked hyperlordosis and late diaphragmatic dysfunction.
Distal Xq28 microduplication syndrome (ORPHA:293939)
A rare syndromic X-linked intellectual disability characterized by cognitive impairment, behavioral and psychiatric problems, obesity, recurrent infections, atopic diseases, and distinctive facial features in males. Females are clinically asymptomatic or mildly affected, presenting mild learning difficulties and facial dysmorphism.
Distomatosis (ORPHA:1685)
A rare group of infectious disease characterized by the infection of different organs (liver, lungs, or intestines) by flat worms live in contact with epitheliums. Clinical symptoms vary depending on the infected organ. In liver infection, (often presents with inflammation and obstruction of the biliary ducts) fever, allergic reactions (dermographism), abdominal pain, nausea, diarrhoea, hypereosinophilia and angiocholitis attacks can be observed. In lung infection, tuberculosis-like clinical signs (cough or haemoptysis) are observed without fever, however erratic cases may also exist. In intestine infection, painful diarrhea, abdominal pain, oedema (face, abdomen or legs), vomiting, anorexia, or intestinal obstruction can be observed, some patients can also be asymptomatic.
DITRA (ORPHA:404546)
A rare, genetic, autoinflammatory syndrome with immune deficiency disease characterized by recurrent and severe flares of generalized pustular psoriasis associated with high fever, asthenia, and systemic inflammation, due to IL36R antagonist deficiency. Psoriatic nail changes (e.g. pitting and onychomadesis) and ichthyosis may occasionally be associated.
DK1-CDG (ORPHA:91131)
DK1-CDG is characterised by muscular hypotonia and ichthyosis. It has been described in four children from two consanguineous families. All the affected children died during early infancy, two from dilated cardiomyopathy. The syndrome is caused by a deficiency in dolichol kinase 1 (DK1), an enzyme involved in the de novo biosynthesis of dolichol phosphate. The mutations identified in the DK1 gene led to a 96 to 98% reduction in DK activity.
DNA2-related mitochondrial DNA deletion syndrome (ORPHA:352470)
A rare, genetic, mitochondrial oxidative phosphorylation disorder characterized by either late-onset myopathy with progressive external ophthalmoplegia and muscular weakness (predominantly limb-girdle) or early-onset myopathy presenting with decreased fetal movements, congenital ptosis, progressive external ophthalmoplegia, hypotonia and, variably, joint contractures. Reduced content and multiple deletions of mitochondrial DNA is observed in muscle biopsy.
DNAJB2-related Charcot-Marie-Tooth disease type 2 (ORPHA:443950)
A rare autosomal recessive axonal hereditary motor and sensory neuropathy characterized by adolescent or adult onset of slowly progressive muscle weakness and atrophy of the distal lower limbs progressing to involve also the upper limbs and proximal muscles, and sensory impairment. Patients present gait disturbances and loss of reflexes, at later stages loss of ambulation, dysarthria, dysphagia, facial weakness, and impairment of respiratory muscles requiring assisted ventilation.
DNAJB6-related limb-girdle muscular dystrophy D1 (ORPHA:34516)
A subtype of autosomal dominant limb-girdle muscular dystrophy characterized by an adult-onset of slowly progressive, proximal pelvic girdle weakness, with none, or only minimal, shoulder girdle involvement, and absence of cardiac and respiratory symptoms. Mild to moderate elevated creatine kinase serum levels and gait abnormalities are frequently observed.
Dobrow syndrome (ORPHA:3262)
A rare multiple congenital defects/dysmorphic syndrome characterized by variable degrees of bony syngnathia associated with variable additional abnormalities, including growth retardation, intellectual disability, microcephaly, iris coloboma, nystagmus, deafness, and vertebral segmentation defects, as well as genital, limb and additional facial malformations, among others.
Dominant beta-thalassemia (ORPHA:231226)
Dominant beta-thalassemia is a form of beta-thalassemia (see this term) resulting in moderate to severe anemia.
Epidemiology
Prevalence of this form is not known.
Clinical description
Patients present with moderate to severe anemia, jaundice and splenomegaly.
Etiology
Rare mutations in the beta-globin HBB gene result in synthesis of extremely unstable beta-globin variants which precipitate in erythroid precursors causing ineffective erythropoiesis.
Diagnostic methods
The presence of hyper-unstable hemoglobin should be suspected in any individual with beta-thalassemia intermedia (see this term) when both parents are hematologically normal (de novo mutations), or in families with a pattern of autosomal dominant transmission of beta-thalassemia intermedia. Diagnosis is based on beta-globin gene sequencing.

                            Last update: 
                            May 2011


                            - Expert reviewer(s): 
                            Pr Renzo GALANELLO  - Dr Raffaella ORIGA
Dominant hypophosphatemia with nephrolithiasis or osteoporosis (ORPHA:244305)
A rare, genetic renal tubular disease characterized by phosphate loss in the proximal tubule, leading to hypercalciuria and recurrent urolithiasis and/or osteoporosis.
Epidemiology
More than 10 cases have been identified to date.
Clinical description
Disease onset is in adulthood with presentation of nephrolithiasis, renal phosphate wasting and skeletal abnormalities variably including osteopenia, osteoporosis and increased susceptibility to fractures. Cases of spinal deformity have also been described.
Etiology
Heterozygous mutations have been identified in two genes SCL34A1 (5q35), and SLC9A3R1 (17q25.1). SCL34A1 encodes the main sodium-phosphate cotransporter, sodium-dependent phosphate transport protein 2A (NPT2a), located in the apical membrane of renal proximal tubular cells.  SLC9A3R1 encodes the Na(+)/H(+) exchange regulatory cofactor (NHERF1), a cytoplasmic protein essential for recruitment of transporter or signaling proteins to the plasma membrane which stabilize NaPi-IIa, the parathyroid hormone (PTH) receptor 1, and phospholipase C at the brush border membrane and creates a platform for PTH signaling to NaPi-IIa . SLC9A3R1 mutations decreases NPT2a expression directly or indirectly via an increase in PTH-responsive downregulation of NaPi-IIa. The decreased serum phosphate levels stimulate 1,25-dihydroxy-Vitamin D synthesis leading to absorptive hypercalciuria, which together with elevated urinary phosphate levels can trigger the formation of calcium-phosphate crystals favoring the development of renal calcifications.
Diagnostic methods
Diagnosis is usually based on clinical features, plasma and urine electrolytes showing hypophosphatemia, hyperphosphaturia, hypercalciuria and increased serum 1,25-dihydroxy-Vitamin D in response to phosphate deprivation. A definitive diagnosis can be achieved by genetic testing.
Differential diagnosis
The differential diagnosis includes other forms of inherited hypophosphatemia such as X-linked hypophosphatemia, autosomal recessive hypophosphatemic rickets, autosomal dominant hypophosphatemic rickets, hereditary hypophosphatemic rickets with hypercalciuria.
Genetic counseling
The pattern of inheritance is autosomal dominant. There is a 50% risk of the disease occurring in a sibling or being transmitted to the offspring of affected individuals.
Management and treatment
Supportive treatment is with phosphate and low‐ dose vitamin D supplementation.
Prognosis
There is no information available on outcomes.

                            Last update: 
                            January 2020


                            - Expert reviewer(s): 
                            Pr Elena LEVTCHENKO | ERKNet*


                                * European Reference Network
Dopa-responsive dystonia (ORPHA:255)
Dopa-responsive dystonia (DRD) describes a group of neurometabolic disorders characterized by dystonia that typically shows diurnal fluctuations, that responds excellently to levodopa (L-dopa) and that is comprised of autosomal dominant dopa-responsive dystonia (DYT5a), autosomal recessive dopa-responsive dystonia (DYT5b) and dopa responsive dystonia due to sepiapterin reductase (SR) deficiency.
Epidemiology
The estimated European prevalence of DRD ranges from 1/1,000,000-1/200,000.
Clinical description
DRD usually has a pediatric onset, typically with lower limb dystonia that leads to gait disturbances and that usually worsens during the course of the day and is improved in the morning after sleeping. Parkinsonism can develop at a later age in some patients. Anxiety, depression, sleep disturbances and obsessive-compulsive disorders have also been reported in a few patients with DYT5a. Rarer subtypes which are inherited in an autosomal recessive manner typically show a much more severe phenotype, with onset in the first year of life with additional manifestations of global developmental delay, axial hypotonia, oculogyric crises and encephalopathy. DRD responds dramatically and continuously to L-dopa therapy, and patients usually experience a significant improvement of symptoms once treatment is initiated. If untreated, patients can become wheelchair bound.
Etiology
DRD is due to mutations in genes that encode proteins essential for the biosynthesis of dopamine. DYT5a is due to mutations in the GTP cyclohydrolase 1 (GCH1) gene (14q22.1 to q22.2) which encodes an enzyme needed for the biosynthesis of tetrahydrobiopterin, the essential co-factor for tyrosine hydroxylase. DYT5b is caused by mutations in the tyrosine hydroxylase TH gene (11p15.5) encoding tyrosine hydroxylase, the enzyme responsible for catalyzing the conversion of tyrosine to L-dopa, the precursor of dopamine. Finally, DRD due to an SRD is due to mutations in the SPR gene (2p14-p12), encoding the enzyme sepiapterin reductase (SR), which is also required for the biosynthesis of tetrahydrobiopterin.
Genetic counseling
DRD can be inherited in an autosomal dominant or autosomal recessive manner, depending on the subtype. It can also occur due to de novo mutations.

                            Last update: 
                            November 2013


                            - Expert reviewer(s): 
                            Dr Christoph KAMM
Double uterus-hemivagina-renal agenesis syndrome (ORPHA:3411)
A rare congenital urogenital anomaly characterized by the presence of double uterus (didelphys, bicornuate or septum-complete or partial), unilateral cervico-vaginal obstruction (obstructed hemivagina-communicant, not communicant or septate and unilateral cervical atresia) and ipsilateral renal anomalies (renal agenesis and/or other urinary tract anomalies). Patients are usually diagnosed at puberty after menarche due to recurrent severe dysmenorrhea, chronic pelvic pain, excessive foul smelling mucopurulent discharge, spotting and intermenstrual bleeding (depending on the existence of uterine or vaginal communications). Fever, dyspareunia, and a palpable abdominal, pelvic or vaginal mass (mucocolpos or pyocolpos) may also be present.
Double-orifice mitral valve (ORPHA:95474)
A rare, congenital, non-syndromic heart malformation characterized by a single fibrous annulus with two orifices opening into the left ventricle. Clinical presentation is variable and related to the degree of resulting mitral insufficiency and/or stenosis, and depending on the associated heart disease, most commonly atrioventricular septal defect, obstructive left-sided lesions, and cyanotic heart disease. Rare cases of isolated disease have been reported.
Dowling-Degos disease (ORPHA:79145)
A rare, genetic, hyperpigmentation of the skin disease characterized by adulthood-onset of reticular, reddish-brown to dark-brown, macular and/or comedone-like, hyperkeratotic papules with hypopigmented macules, predominantly affecting flexural areas and, on occasion, progressing to involve trunk and acral regions. Histologically, epidermal acanthosis, thin, branch-like, rete ridges, and a tendency for acantholysis and pigmentary incontinence is observed.
DPAGT1-CDG (ORPHA:86309)
DPAGT1-CDG is a form of congenital disorders of N-linked glycosylation characterized by hypotonia, intractable seizures, developmental delay, microcephaly and severe fetal hypokinesia. Additional features that may be observed include apnea and respiratory deficiency, cataracts, joint contractures, vermian hypoplasia, dysmorphic features (esotropia, arched palate, micrognathia, finger clinodactyly, single flexion creases) and feeding difficulties. The disease is caused by loss-of-function mutations in the gene DPAGT1  (11q23.3).
DPM1-CDG (ORPHA:79322)
A rare disorder of multiple glycosylation pathways characterized by global developmental delay, motor skills delay, hypotonia, seizures, microcephaly and eye abnormalities (including retinopathy, nystagmus, strabismus) with varying onset and severity. Additional clinical features may include peripheral neuropathy, dysmorphic features (facial and limb abnormalities), ataxia and severe gastrointestinal involvement.
DPM3-CDG (ORPHA:263494)
DPM3-CDG is an extremely rare form of CDG syndrome (see this term) characterized clinically in the single reported case by muscle weakness, waddling gait and dilated cardiomyopathy (see this term).
Drug or radiation exposure-related interstitial lung disease (ORPHA:264978)
A rare secondary interstitial lung disease (ILD) characterized by development of the condition after exposure to certain drugs or radiation therapy. Diagnostic criteria include clear temporal association, identification of a characteristic reaction pattern to the respective drug, and exclusion of other causes of the ILD. Clinically, drug-induced ILD (DI-ILD) may occur as acute ILD with respiratory failure, or as subacute/chronic DI-ILD. Radiation injury to the lung can develop during or following radiation therapy and depends on the nature and dose of the ionizing radiation, as well as the direction of the radiation beam.
Drug reaction with eosinophilia and systemic symptoms (ORPHA:139402)
A rare hypersensitivity reaction characterized by a generalized infiltrated skin rash with face edema, fever, enlarged lymph nodes, eosinophilia, lymphocytosis and more or less severe visceral involvement (e.g. hepatitis, nephritis, pneumonitis, myocarditis ect.) and, in some patients, reactivation of human herpes virus 6, Epstein-Barr virus and/or cytomegalovirus. Onset usually occurs 2-8 weeks after administration of the causal medication and is most frequently associated with anticonvulsants, antibacterial sulfonamides and allopurinol but many other medications have also been implicated. Histology is characterized by interface dermatitis, sometimes mixed with eczematous and an acute generalized exanthematous pustulosis-like pattern. Auto-immune sequelae may occur.