TaoMedAI/RareMedData huggingface dataset:
Dysplasia of head of femur, Meyer type (ORPHA:168621)
Meyer dysplasia of the femoral head is a mild localized form of skeletal dysplasia characterized by delayed, irregular ossification of femoral capital epiphysis.
Epidemiology
Prevalence is unknown.
Clinical description
The condition is often discovered incidentally during early childhood (during the second or third year of life). It is often bilateral, although severity may be asymmetric. Clinical manifestations may include a waddling gait, genu valgum, hip pain and restricted movement, although these manifestations are usually transient and the majority of patients are asymptomatic. Resolution without treatment by six years of age has been reported in some cases, however, permanent deformity (flattening) of the femoral head has also been described and could represent a mild form of multiple epiphyseal dysplasia (see this term).

                            Last update: 
                            November 2008


                            - Expert reviewer(s): 
                            Dr Martine LE MERRER
Dysplastic cortical hyperostosis, Kozlowski-Tsuruta type (ORPHA:2204)
Dysplastic cortical hyperostosis is an extremely rare primary bone dysplasia with increased bone density characterized by lethal neonatal dwarfism with hydrops, narrow chest and short limbs with extensive cortical thickening of all long bones, ribs, clavicles and scapulae, and coronal clefts in vertebral bodies.
Dysraphism-cleft lip/palate-limb reduction defects syndrome (ORPHA:2476)
A rare developmental defect during embryogenesis disorder characterized by spinal dysraphism, cleft lip and palate, limb reduction defects and anencephaly. There have been no further descriptions in the literature since 1994.
Dyssegmental dysplasia, Silverman-Handmaker type (ORPHA:1865)
Dyssegmental dysplasia, Silverman-Handmaker type is a rare, genetic, primary bone dysplasia disorder, and lethal form of neonatal short-limbed dwarfism, characterized by anisospondyly, severe short stature and limb shortening, metaphyseal flaring and distinct dysmorphic features (i.e. flat facial appearance, abnormal ears, short neck, narrow thorax). Additional features may include other skeletal findings (e.g. joint contractures, bowed limbs, talipes equinovarus) and urogenital and cardiovascular abnormalities.
Dysspondyloenchondromatosis (ORPHA:85198)
Dysspondyloenchondromatosis is a rare skeletal dysplasia characterized by anisospondyly and multiple enchondromas in vertebrae and the metaphyseal and diaphyseal parts of long tubular bones, leading to kyphoscoliosis and lower limb asymmetry.
Dystonia 16 (ORPHA:210571)
Dystonia 16 (DYT16) is a very rare and newly discovered movement disorder which is characterized by early-onset progressive limb dystonia, laryngeal and oromandibular dystonia, and parkinsonism.
Epidemiology
It has been described in 8 patients from three Brazilian families and one German family to date.
Clinical description
Disease presents in infancy to late childhood with one of two possible phenotypes: either generalized dystonia or dystonia-parkinsonism not responsive to L-Dopa. Dystonia usually starts in one limb, becomes generalized and mainly affects the trunk, neck and oromandibular muscles. Motor and speech developmental delays were also reported. The phenotypic spectrum of this disease is still being determined. Pharmacological therapy is ineffective.
Etiology
DYT16 is caused by mutations in the protein kinase, interferon-inducible double stranded RNA dependent activator (PRKRA) gene, located on chromosome 2q31.2.
Genetic counseling
DYT16 is inherited in an autosomal recessive manner, and genetic counseling is possible and recommended.

                            Last update: 
                            November 2013


                            - Expert reviewer(s): 
                            Dr Christoph KAMM
Dystonia 28 (ORPHA:589618)
A rare persistent combined dystonia characterized by childhood onset of progressive dystonia typically beginning in the lower limbs and eventually progressing to generalized dystonia with involvement of the upper limbs, trunk, face, and neck. Variable developmental delay and intellectual disability, as well as mild microcephaly, short stature, abnormal eye movements, and slightly dysmorphic facial features have been reported in association.
Dystonia-aphonia syndrome (ORPHA:412217)
Dystonia-aphonia syndrome is a rare, genetic, persistent combined dystonia disorder characterized by slowly progressive, severe, caudo-rostrally spreading generalized dystonia with prominent facial and oro-mandibular involvement leading to severe anarthria and/or aphonia, swallowing difficulties, and gait disturbances. Additional manifestations include slowed horizontal saccades, subclinical epilepsy, photic myoclonus, oral hypertrophic changes (e.g. gingival or lingual hyperplasia), as well as delayed milestones and cognitive impairment.
Dystonia-parkinsonism-hypermanganesemia syndrome (ORPHA:521406)
A rare disorder of manganese transport characterized by progressive movement disorder and elevated blood manganese levels. Patients present in infancy or early childhood with loss of motor milestones, rapidly progressive dystonia, spasticity, bulbar dysfunction, and parkinsonism, resulting in loss of independent ambulation. Cognition may be impaired but is generally better preserved than motor function. Additional manifestations include abnormal head growth and skull deformities. Brain MRI shows abnormalities of the basal ganglia, variably also of other brain regions.
Dystrophic epidermolysis bullosa pruriginosa (ORPHA:89843)
A rare dystrophic epidermolysis bullosa (DEB) characterized by generalized or localized skin lesions associated with severe, if not intractable, pruritus.
Epidemiology
Prevalence is unknown. Approximately 100 families or sporadic cases have been reported to date, but it might be underreported.
Clinical description
While skin fragility and blistering lesions usually manifest in infancy, which heal with atrophic scarring and milia formation, the onset of intense pruritus is frequently delayed until the adolescence or even adulthood. At the onset of pruritus, the clinical picture generally worsens with the development of papules, nodules, lichenoid and hypertrophic lesions in a linear distribution, preferentially on the extensor surfaces of the limbs. Nail dystrophy is usually present.
Etiology
DEB pruriginosa is caused by mutations within the type VII collagen gene (COL7A1/i>; 3p21.31). Mutations in this gene lead to an alteration in function or to reduced amounts of collagen VII. This impairs its assembly into anchoring fibrils that anchor the basement membrane to the underlying dermis.
Diagnostic methods
Transmission electron microscopy shows blister formation below the lamina densa and reduced number of anchoring fibrils in adjacent non-blistered skin. Immunofluorescence mapping shows dermal cleavage of the skin and reduced immunoreactivity for type VII collagen. The diagnosis is confirmed by genetic testing.
Differential diagnosis
Differential diagnosis includes nodular prurigo, lichen simplex, lichen planus, hypertrophic scarring and dermatitis artefacta.
Antenatal diagnosis
Antenatal diagnosis is not recommended.
Genetic counseling
The disorder is typically sporadic but autosomal dominant and recessive inheritance has also been reported. Genetic counselling should be offered to affected individuals informing them of risk of transmitting the pathogenic variant to offspring.
Management and treatment
Clinical management of DEB pruruginosa is often difficult, although generic measures reduce itching. Nevertheless, there are some reports of helpful interventions which include topical treatments (e.g. tacrolimus), systemic agents (e.g. ciclosporin or thalidomide), and cryotherapy. Recently, dupilumab has proven to be effective.
Prognosis
The condition is therapy resistant, but the overall course of the disease is mild to moderate and life expectancy is normal.

                            Last update: 
                            May 2021


                            - Expert reviewer(s): 
                            Pr Cristina HAS | ERN-Skin* - Pr Carmen SALAVASTRU | ERN-Skin*


                                * European Reference Network
Ear-patella-short stature syndrome (ORPHA:2554)
A rare microcephalic primordial dwarfism characterized by the association of bilateral microtia (severe hypoplasia of ear pinnae), absent patellae, short stature and characteristic facial features such as high forehead, micrognathism with full lips and small mouth, and accentuated nasolabial folds (smile wrinkles linking the nostrils to the labial commissure).
Early myoclonic encephalopathy (ORPHA:1935)
A rare disorder characterized clinically by the onset of fragmentary myoclonus appearing in the first month of life, often associated with erratic focal seizures and a suppression-burst EEG pattern.
Epidemiology
The prevalence is unknown but Early myoclonic encephalopathy is a rare disease with only around 30 cases described so far.
Clinical description
Onset sometimes occurs as early as a few hours after birth, and postnatal movements are sometimes reported by the mother to be of the same type as those felt at the end of pregnancy. Other types of seizures, including partial seizures, massive myoclonia, and tonic spasms can also occur; usually at around 3-4 months of age. Neurological abnormalities are constant: very severe delay in psychomotor acquisitions, marked hypotonia, and disturbed alertness, sometimes with a vegetative state. Signs of peripheral neuropathy may also occur in rare cases.
Etiology
Although the etiology is mostly unknown, nonketotic hyperglycinemia, pyridoxine or pyridoxal-phosphate dependency, together with congenital deficiency of the mitochondrial glutamate transporter are known to produce a similar clinical picture. Therefore, this condition may result from excess glutamate delivery in the synaptic cleft by the end of pregnancy.
Genetic counseling
There is a high risk of familial recurrence since in most cases the disease appears to be inherited as an autosomal recessive trait.
Management and treatment
There is no effective treatment.
Prognosis
The prognosis is poor: children with the condition survive in a persistent vegetative state or die within the first or second year of life.

                            Last update: 
                            October 2006


                            - Expert reviewer(s): 
                            Pr Olivier DULAC
Early onset non-syndromic cataract (ORPHA:91492)
A rare, genetic, non-syndromic developmental defect of the eye disorder, with high clinical and genetic heterogeneity, most frequently characterized by bilateral, symmetrical, non-progressive cataracts which present at birth or in early-childhood. Additional ocular manifestations (e.g. anterior segment dysgenesis, colobomas, nystagmus, microcornea, microphthalmia, myopia) may be associated, however other organs/systems are usually not affected.
Early-onset autosomal dominant Alzheimer disease (ORPHA:1020)
Early-onset autosomal dominant Alzheimer disease (EOAD) is a progressive dementia with reduction of cognitive functions. EOAD presents the same phenotype as sporadic Alzheimer disease (AD) but has an early age of onset, usually before 60 years old.
Epidemiology
EOAD represents less than 1% of all cases of AD.
Clinical description
Initial findings of EOAD are mainly disorders of episodic memory or changes in behavior. The patient is often anosognosic and the diagnosis is therefore carried out with the help of a family member. Neurological signs that can be associated with EOAD are spastic paraparesis, intracerebral hemorrhages, seizures, extrapyramidal syndrome and exceptionally cerebellar ataxia.
Etiology
EOAD is the consequence of either PSEN1 mutations (69%), APP mutations (13%), or APP duplication (7,5%), and exceptionally of PSEN2 mutations (2%). These mutations result in an incompletely understood cascade of events resulting in neuronal death, synapse loss, and the formation of neurofibrillary tangles and senile plaques.
Diagnostic methods
EOAD is diagnosed using the clinical criteria of the NINCDS-ADRDA(McKahnn, 1984). Brain imaging can be normal. Lumbar puncture for measurement of cerebrospinal fluid tau and amyloid may be useful (tau and phosphorylated tau are often elevated and amyloid is usually low). Age of onset before 60 years suggests an EOAD and needs a pedigree.
Differential diagnosis
Differential diagnosis includes depression and other young dementias such as frontotemporal dementia, Lewy body dementia and Huntington disease (see these terms).
Genetic counseling
Genetic counseling should be offered to the families.
Management and treatment
Management is symptomatic and includes the use of cholinesterase inhibitors and partial N-methyl-D-aspartate antagonists. Psychotrops may also be useful.
Prognosis
The disease is progressive; patients have deterioration in their behavior, cognition, and ability to perform activities of daily living. At an advanced stage, patients are confined to bed.

                            Last update: 
                            December 2009


                            - Expert reviewer(s): 
                            Dr Lucie GUYANT-MARECHAL
Early-onset calcifying leukoencephalopathy-skeletal dysplasia (ORPHA:556985)
A rare genetic neurological disorder characterized by pediatric onset of calcifying leukoencephalopathy and skeletal dysplasia. Reported structural brain abnormalities include agenesis of corpus callosum, ventriculomegaly, congenital hydrocephalus, pontocerebellar hypoplasia, periventricular calcifications, Dandy-Walker malformation and absence of microglia. Characteristic skeletal features include increased bone mineral density (reported in skull, pelvic bone and vertebrae), platyspondyly, and under-modeling of tubular bones with widened/radiolucent metaphysis and constricted/sclerotic diaphysis.
Early-onset cerebellar ataxia with retained tendon reflexes (ORPHA:1177)
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.
Epidemiology
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.
Clinical description
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). 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.
Etiology
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.
Diagnostic methods
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
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 disorders that may express ataxia.
Genetic counseling
Transmission is autosomal recessive. The parents of an affected child should be informed of the 25% risk of transmitting the disease to future offspring.
Management and treatment
Treatment is symptomatic, aimed towards the control of spasticity, and should include physiotherapy and pharmacotherapy (that may include spasmolytic drugs such as baclofen).
Prognosis
The period of latency before becoming wheelchair-bound is significantly longer in EOCARR than in FRDA, resulting in a better prognosis in patients with EOCARR than in those with FRDA.

                            Last update: 
                            January 2014


                            - Expert reviewer(s): 
                            Pr Francesc PALAU
Early-onset epilepsy-intellectual disability-brain anomalies syndrome (ORPHA:488635)
A rare congenital disorder of glycosylation characterized by early onset of hypotonia, severe global developmental delay, intellectual disability, and seizures. Ataxia, mild facial dysmorphism, and autistic behavior have also been reported. Brain MRI findings are variable and include cerebral atrophy, cerebellar hypoplasia/atrophy, and thin corpus callosum.
Early-onset epileptic encephalopathy and intellectual disability due to GRIN2A mutation (ORPHA:289266)
Early-onset epileptic encephalopathy and intellectual disability due to GRIN2A mutation is a rare intellectual disability and epilepsy syndrome characterized by global developmental delay and mild to profound intellectual disability, multiple types of usually intractable focal and generalized seizures with variable abnormal EEG findings, and bilateral progressive parenchymal volume loss and thin corpus callosum on brain MRI.
Early-onset epileptic encephalopathy-cortical blindness-intellectual disability-facial dysmorphism syndrome (ORPHA:411986)
Early-onset epileptic encephalopathy-cortical blindness-intellectual disability-facial dysmorphism syndrome is a rare, syndromic intellectual disability syndrome characterized by cortical blindness, different types of seizures, intellectual disability with limited or absent speech, and dysmorphic facial features. Brain imaging typically shows mild pontine hypoplasia, hypoplasia of the corpus callosum and atrophy in the occipital region.
Early-onset familial hypoaldosteronism (ORPHA:556030)
A rare type of familial hypoaldosteronism characterized by early infantile onset of vomiting, diarrhea, severe dehydration, and failure to thrive. Analysis of plasma electrolytes shows hyponatremia, hyperkalemia, and acidosis. Plasma renin activity is elevated, and aldosterone levels are low.
Early-onset Lafora body disease (ORPHA:324290)
A rare genetic progressive myoclonic epilepsy characterized by childhood onset of progressive dysarthria, myoclonus, ataxia, seizures, and cognitive decline. The disease takes a protracted course with patients surviving into adulthood, developing signs and symptoms like psychosis with outbursts of prolonged agitation and screaming, spasticity and hyperreflexia, confusion, mutism, and incontinence. There are no visual disturbances. Muscle biopsy shows numerous periodic acid-Schiff-positive inclusions, so-called Lafora bodies.
Early-onset myopathy with fatal cardiomyopathy (ORPHA:289377)
A rare genetic neuromuscular disease characterized by neonatal or infancy onset of delayed motor development, generalized muscle weakness involving also the facial muscles, pseudohypertrophy of lower limb muscles, and joint contractures, associated with childhood onset of rapidly progressive dilated cardiomyopathy with arrhythmias leading to sudden cardiac death. Muscle biopsy in early childhood shows minicore-like lesions and centralized nuclei, with dystrophic features being more conspicuous in the second decade of life.
Early-onset myopathy-areflexia-respiratory distress-dysphagia syndrome (ORPHA:439212)
A rare congenital myopathy characterized by early onset of severe muscular weakness, respiratory distress due to diaphragmatic paralysis, dysphagia and areflexia, joint contractures, and scoliosis. Decreased fetal movements are seen in some individuals. Muscle biopsy may show a combination of dystrophic and myopathic features. The clinical course is variable, with some patients becoming ventilator-dependent and never achieving ambulation.
Early-onset parkinsonism-intellectual disability syndrome (ORPHA:2379)
A rare X-linked syndromic intellectual disability characterized by infantile-onset non-progressive intellectual deficit (with psychomotor developmental delay, cognitive impairment and macrocephaly) and early-onset parkinsonism (before 45 years of age), in male patients.
Early-onset progressive encephalopathy with migrant continuous myoclonus (ORPHA:1943)
A rare disorder characterized by early-onset progressive encephalopathy with migrant, continuous myoclonus. Three cases have been reported. The focal continuous myoclonus appeared during the first months of life. Prolonged bilateral myoclonic seizures and generalized tonic-clonic seizures occurred later. Subsequently, a progressive encephalopathy with hypotonia and ataxia appeared. Cortical atrophy was revealed by computed tomography (CT) scan and magnetic resonance imaging (MRI). The aetiology is unknown.
Early-onset progressive encephalopathy-spastic ataxia-distal spinal muscular atrophy syndrome (ORPHA:496756)
A rare genetic neurodegenerative disease characterized by neonatal to infantile onset of hypotonia, developmental delay, regression of motor skills with distal amyotrophy, ataxia, and spasticity, absent speech or dysarthria, and moderate to severe cognitive impairment. Optic atrophy may also be associated. Brain imaging shows cerebellar atrophy and thin corpus callosum, as well as brain iron accumulation in the pallidum and substantia nigra beginning during the second decade of life.
Early-onset progressive leukoencephalopathy-central nervous system calcification-deafness-visual impairment syndrome (ORPHA:3240)
A rare genetic neurological disorder characterized by early-onset progressive leukoencephalopathy, severe developmental delay, early-onset or congenital deafness (only few cases reported without hearing loss), and visual impairment. All patients manifest calcifications in brain and spinal cord. Cognitive impairment, seizures, hypotonia, spastic tetraplegia or quadriplegia are observed in the majority of the patients. Variable features may include microcephaly and anemia.
Early-onset progressive neurodegeneration-blindness-ataxia-spasticity syndrome (ORPHA:352654)
A rare, genetic, neurodegenerative disease characterized by normal early development followed by childhood onset optic atrophy with progressive vision loss and eventually blindness, followed by progressive neurological decline that typically includes cerebellar ataxia, nystagmus, dorsal column dysfunction (decreased vibration and position sense), spastic paraplegia and finally tetraparesis.
Early-onset seizures-distal limb anomalies-facial dysmorphism-global developmental delay syndrome (ORPHA:505237)
A rare genetic multiple congenital anomalies/dysmorphic syndrome characterized by variable developmental delay, intellectual disability, early-onset seizures, and facial dysmorphism (including arched eyebrows, long palpebral fissures, prominent nasal bridge, large ears, thin upper lip, and high arched palate). Other reported features are microcephaly, hypotonia, growth retardation, congenital heart defects, and malformations of the fingers and toes, as well as additional neurologic manifestations (such as ataxia or spastic quadriplegia). Brain imaging may show hypoplastic corpus callosum, white matter abnormalities, or cortical atrophy.