TaoMedAI/RareMedData huggingface dataset:
Progeroid features-hepatocellular carcinoma predisposition syndrome (ORPHA:435953)
A rare inherited cancer-predisposing syndrome characterized by early-onset hepatocellular carcinoma, genomic instability, and progeroid features, such as short stature, low body weight, muscular atrophy, lipodystrophy, bilateral cataracts, and premature hair graying. Dysmorphic craniofacial features include triangular face, small, deep-set eyes, and micrognathia. Kyphoscoliosis, sloping shoulders, mild pectus excavatum, bilateral contractures of the elbows and fingers, bilateral clinodactyly, and pes planus have also been reported.
Progeroid syndrome, Petty type (ORPHA:2963)
Progeroid syndrome, Petty type is a rare premature aging syndrome characterized by pre-and postnatal growth retardation, a congenital premature-aged appearance with distinctive craniofacial dysmorphism (wide calvaria with large open anterior fontanel and wide metopic suture, broad forehead, small face, micrognathia), markedly diminished subcutaneous fat, cutis laxa and wrinkled skin, without delay in psychomotor development. Scant, brittle hair, hypoplastic nails and delayed, abnormal dentition, as well as hypoplastic distal phalanges, umbilical hernia and eye abnormalities (myopia/hyperopia, strabismus), are also commonly associated.
Progressive autosomal recessive ataxia-deafness syndrome (ORPHA:448251)
A rare genetic disease characterized by severe progressive sensorineural hearing loss and progressive cerebellar signs including gait ataxia, action tremor, dysmetria, dysdiadochokinesis, dysarthria, and nystagmus. Absence of deep tendon reflexes has also been reported. Age of onset is between infancy and adolescence. Brain imaging may show variable cerebellar atrophy in some patients.
Progressive bifocal chorioretinal atrophy (ORPHA:75373)
Progressive bifocal chorioretinal atrophy (PBCRA) is an early-onset chorioretinal dystrophy characterized by large atrophic macular and nasal retinal lesions, nystagmus, myopia, poor vision, and slow disease progression.
Epidemiology
It has been described in two large families.
Etiology
Transmission is autosomal dominant and the causative gene has been mapped to a region on chromosome 6q, close to the macular dystrophy retinal 1 (MCDR1) locus.

                            Last update: 
                            September 2006
Progressive cavitating leukoencephalopathy (ORPHA:139447)
A rare leukoencephalopathy characterized by acute episodes of neurological deficit (ataxia, dysarthria, seizures) with irritability and opisthotonus followed by either steady deterioration or alternating periods of rapid progression and prolonged periods of stability.
Epidemiology
So far around 20 patients have been reported in the literature.
Clinical description
Onset occurs in infancy or early childhood.
Etiology
The etiology remains unknown.
Diagnostic methods
MRI imaging reveals irregular asymmetric patches of leukoencephalopathy with cavities, vascular permeability and cystic degeneration affecting principally the corpus callosum, cerebral and cerebellar white matter, and spinal cord.
Genetic counseling
The mode of transmission is autosomal recessive.

                            Last update: 
                            September 2008
Progressive cerebello-cerebral atrophy (ORPHA:247198)
A rare genetic neurological disorder characterized by postnatal onset of severe global developmental delay, profound mental retardation, progressive microcephaly, progressive spasticity evolving into spastic quadriplegia with joint contractures, generalized seizures, and irritability. Severe choreoathetosis and dysmorphic features are absent. Brain imaging shows progressive cerebellar atrophy followed by cerebral atrophy affecting both white and grey matter, but no pontine involvement.
Progressive cone dystrophy (ORPHA:1871)
A rare retinal dystrophy characterized by photophobia, progressive loss of visual acuity, nystagmus, visual field abnormalities, abnormal color vision, and psychophysical and electrophysiological evidence of abnormal cone function. Progressive cone dystrophy usually presents in childhood or early adult life, and patients tend to develop rod photoreceptor dysfunction in later life.
Progressive encephalomyelitis with rigidity and myoclonus (ORPHA:438266)
A rare stiff person syndrome spectrum disorder characterized by limb and truncal rigidity, stimulus-sensitive spasms, myoclonus, hyperekplexia, autonomic disturbance, and brainstem involvement or other neurological defects. The condition is progressive and potentially life-threatening, especially due to respiratory failure. It may be associated with the presence of glycine receptor or glutamic acid decarboxylase antibodies, as well as thymomas or lymphomas.
Progressive encephalopathy with leukodystrophy due to DECR deficiency (ORPHA:431361)
Progressive encephalopathy with leukodystrophy due to DECR deficiency is a rare mitochondrial disease, which presents with neonatal hypotonia, central nervous system abnormalities (ventriculomegaly, corpus callosum hypoplasia, cerebellar atrophy), acquired microcephaly, failure to thrive, developmental delay and intermittent lactic acidosis provoked by catabolic stress (e.g. infection). Hyperlysinemia and elevated C10:2 carnitine can be detected in plasma. Later on, epilepsy, cerebellar ataxia, renal tubular acidosis, severe encephalopathy, dystonia, spastic quadriplegia and other complications may develop.
Progressive epilepsy-intellectual disability syndrome, Finnish type (ORPHA:1947)
Progressive epilepsy-intellectual deficit, Finnish type (also known as Northern epilepsy) is a subtype of neuronal ceroid lipofuscinosis (NCL; see this term) characterized by seizures, progressive decline of intellectual capacities and variable loss of vision.
Epidemiology
Prevalence is unknown but the disorder is principally reported in Northern Finland.
Clinical description
The disorder is characterized by generalized tonic-clonic seizures with onset at 5 to 10 years of age and subsequent slowly progressive mental deterioration. The seizures increase in frequency until puberty after which the epileptic activity starts to decline. The intellectual deficit is severe, develops 2-5 years after the onset of seizures and progresses continuously through adulthood. Visual problems are not a prominent feature of this disorder; if present they may be mild and go unrecognized.
Etiology
Progressive epilepsy-intellectual deficit, Finnish type is caused by mutations in the CLN8 gene (8p23.3) encoding a putative transmembrane protein of unknown function.
Diagnostic methods
Diagnosis is based on the clinical picture, family history and electron microscopy studies of tissue specimens showing intracellular accumulation of storage material. The diagnosis can be confirmed by molecular analysis.
Differential diagnosis
The differential diagnosis should include other causes of dementia and seizures starting at school age, including atypical forms of other NCL disorders (typically juvenile NCL (see this term) caused by mutations in PPT1 (CLN1 disease), TPP1 (CLN2 disease), or CTSD (CLN10 disease)), as well as mitochondrial disorders and chronic types of encephalitis (see these terms).
Antenatal diagnosis
Prenatal diagnosis is feasible for families in which the disease-causing mutation has already been identified and genetic counseling should be provided.
Genetic counseling
Progressive epilepsy-intellectual deficit, Finnish type is transmitted in an autosomal recessive manner
Management and treatment
Treatment is supportive only with palliative care including administration of anticonvulsants, as well as educational, psychological, and psychiatric management.
Prognosis
Although patients suffer from slow cognitive decline, life expectancy is less severely reduced than in other forms of NCL with juvenile onset and patients may reach 50 or 60 years of age.

                            Last update: 
                            February 2010


                            - Expert reviewer(s): 
                            Pr Alfried KOHLSCHÜTTER
Progressive essential tremor-speech impairment-facial dysmorphism-intellectual disability-abnormal behavior syndrome (ORPHA:457212)
A rare genetic syndromic intellectual disability characterized by global developmental delay, moderate to severe intellectual disability, motor and language impairment, behavioral abnormalities (with mood instability, aggression, and self-mutilation), and progressive hand tremor. Facial dysmorphism includes narrow palpebral fissures, large ears, long philtrum, and prominent chin.
Progressive external ophthalmoplegia-myopathy-emaciation syndrome (ORPHA:352447)
Progressive external ophthalmoplegia-myopathy-emaciation syndrome is a rare mitochondrial oxidative phosphorylation disorder due to nuclear DNA anomalies characterized by progressive external ophthalmoplegia without diplopia, cerebellar atrophy, proximal skeletal muscle weakness with generalized muscle wasting, profound emaciation, respiratory failure, spinal deformity and facial muscle weakness (manifesting with ptosis, dysphonia, dysphagia and nasal speech). Intellectual disability, gastrointestinal symptoms (e.g. nausea, abdominal fullness, and loss of appetite), dilated cardiomyopathy and renal colic have also been reported.
Progressive familial intrahepatic cholestasis (ORPHA:172)
Progressive familial intrahepatic cholestasis (PFIC) refers to a heterogeneous group of autosomal recessive disorders of childhood that disrupt bile formation and present with cholestasis of hepatocellular origin.
Epidemiology
The exact prevalence remains unknown, but the estimated prevalence at birth varies between 1/50,000 and 1/100,000.
Clinical description
Three types of PFIC have been identified and are related to mutations in hepatocellular transport system genes involved in bile formation. PFIC1 and PFIC2 (see these terms) usually appear in the first months of life, whereas onset of PFIC3 (see this term) may also occur later in infancy, in childhood or even during young adulthood. Main clinical manifestations include cholestasis, pruritus and jaundice. Serum gamma-glutamyltransferase (GGT) activity is normal in PFIC1 and PFIC2 patients, but is elevated in PFIC3 patients. Additional manifestations may include short stature, sensorineural deafness, watery diarrhea, pancreatitis, elevated sweat electrolyte concentration and liver steatosis.
Etiology
Both PFIC1 and PFIC2 are caused by impaired bile salt secretion due respectively to defects in ATP8B1 encoding the FIC1 protein, and in ABCB11 encoding the bile salt export pump protein (BSEP). Defects in ABCB4, encoding the multi-drug resistant 3 protein (MDR3), impair biliary phospholipid secretion resulting in PFIC3.
Diagnostic methods
Diagnosis is based on clinical manifestations, liver ultrasonography, cholangiography and liver histology, as well as on specific tests for excluding other causes of childhood cholestasis. MDR3 and BSEP liver immunostaining, and analysis of biliary lipid composition should help to select PFIC candidates in whom genotyping could be proposed to confirm the diagnosis.
Differential diagnosis
Differential diagnoses include diseases that present with progressive cholestatic liver disease of childhood.
Antenatal diagnosis
Antenatal diagnosis can be proposed for affected families in which a mutation has been identified.
Management and treatment
Ursodeoxycholic acid (UDCA) therapy should be initiated in all patients to prevent liver damage. In some PFIC1 or PFIC2 patients, biliary diversion can also relieve pruritus and slow disease progression. However, most PFIC patients are ultimately candidates for liver transplantation. Monitoring of hepatocellular carcinoma, especially in PFIC2 patients, should be offered from the first year of life. Hepatocyte transplantation, gene therapy or specific targeted pharmacotherapy may represent alternative treatments in the future.
Prognosis
PFIC patients usually develop fibrosis and end-stage liver disease before adulthood.

                            Last update: 
                            May 2011


                            - Expert reviewer(s): 
                            Dr Christiane BAUSSAN  - Pr Emmanuel GONZALES  - Pr Emmanuel JACQUEMIN  - Dr Anne SPRAUL
Progressive microcephaly-seizures-cortical blindness-developmental delay syndrome (ORPHA:477814)
Progressive microcephaly-seizures-cortical blindness-developmental delay syndrome is a rare, genetic, neuro-ophthalmological syndrome characterized by post-natal, progressive microcephaly and early-onset seizures, associated with delayed global development, bilateral cortical visual impairment and moderate to severe intellectual disability. Additional manifestations include short stature, generalized hypotonia and pulmonary complications, such as recurrent respiratory infections and bronchiectasis. Auditory and metabolic screenings are normal.
Progressive muscular atrophy (ORPHA:454706)
A rare motor neuron disease characterized by isolated lower motor neuron features, including progressive flaccid weakness, muscle atrophy, fasciculations, and reduced or absent tendon reflexes. Onset is in late adulthood, with men being affected more often than women. Upper motor neuron signs may develop later in some cases. Occurrence of respiratory insufficiency determines the prognosis. Neuropathological analysis shows intraneuronal Bunina bodies and ubiquitin-positive inclusions.
Progressive myoclonic epilepsy type 3 (ORPHA:263516)
A rare, genetic, neuronal ceroid lipofuscinosis disorder characterized by infantile- to early childhood-onset of progressive myoclonic seizures (occasionally accompanied by generalized tonic-clonic seizures) and severe, progressive neurological regression, leading to psychomotor and cognitive decline, cerebellar ataxia, dementia and, frequently, early death. Vision loss may be associated. EEG typically reveals epileptiform activity with predominance in the posterior region and photosensitivity.
Progressive myoclonic epilepsy type 5 (ORPHA:402082)
A rare, genetic neurological disorder characterized by early-onset progressive ataxia associated with myoclonic seizures, generalized tonic-clonic seizures (which are often sleep-related), and normal to mild intellectual disability. Dysarthria, upward gaze palsy, sensory neuropathy, developmental delay and autistic disorder have also been associated.
Progressive myoclonic epilepsy type 6 (ORPHA:280620)
A rare, genetic, neurological disorder characterized by early-onset, progressive ataxia associated with myoclonic seizures (frequently associated with other seizure types such as generalized tonic-clonic, absence and drop attacks), scoliosis of variable severity, areflexia, elevated creatine kinase serum levels, and relative preservation of cognitive function until late in the disease course.
Progressive myoclonic epilepsy type 7 (ORPHA:435438)
A rare, genetic, neurological disorder characterized by childhood to adolescent onset of progressive myoclonus (which becomes very severe and results in major motor impediment) associated with infrequent tonic-clonic seizures, and, occasionally, ataxia. Learning disability prior to seizure onset and mild cognitive decline may be associated.
Progressive myoclonic epilepsy type 8 (ORPHA:424027)
A rare, genetic, neurological disorder characterized by childhood to adolescent-onset of action myoclonus, generalized tonic-clonic seizures, and slowly progressive, moderate to severe cognitive impairment that may lead to dementia. EEG reveals progressive slowing of background activity and epileptic abnormalities and brain MRI shows cerebellar and brainstem atrophy.
Progressive myoclonic epilepsy type 9 (ORPHA:457265)
A rare, genetic, neurological disorder characterized by childhood-onset severe myoclonic and tonic-clonic seizures and early-onset ataxia leading to severe gait disturbances associated with normal to slightly diminished cognition. Scoliosis, diffuse muscle atrophy and subcutaneous fat loss, as well as developmental delay, may be associated. Brain MRI may reveal complete agenesis of the corpus callosum, ventriculomegaly, interhemispheric cysts, and simplified gyration (frontally).
Progressive myoclonic epilepsy with dystonia (ORPHA:352596)
Progressive myoclonic epilepsy with dystonia is a rare, genetic epilepsy syndrome characterized by neonatal or early infantile onset of severe, progressive, typically frequent and prolonged myoclonic seizures that are refractory to treatment, associated with localized and/or generalized paroxysmal dystonia (which later becomes persistent). Other features include severe hypotonia, hemiplegia, psychomotor regression (or lack of psychomotor development) and progressive cerebral and cerebellar atrophy, with affected individuals becoming progressively non-reactive to environmental stimuli.
Progressive nodular histiocytosis (ORPHA:158022)
Progressive nodular histiocytosis is a rare, normolipemic, non-Langerhans cell histiocytosis characterized by progressive growth of multiple to disseminated, asymptomatic skin lesions that range in appearance from yellow plaques to coalescence-prone red-brown papules, nodules and pedunculated tumors up to 5 cm in size, located typically on the face, trunk and extremities (and rarely on conjuctiva and mucous membranes). Characteristic microscopic findings include a storiform spindle cell infiltrate in the deep dermis with xanthomatized macrophages and some Touton cells in the upper dermis. It is usually not associated with systemic disease.
Progressive non-fluent aphasia (ORPHA:100070)
Progressive non-fluent aphasia (PNFA) is a form of frontotemporal dementia (FTD; see this term), characterized by agrammatism, laborious speech, alexia, and agraphia, frequently accompanied by apraxia of speech (AOS). Language comprehension is relatively preserved.
Progressive osseous heteroplasia (ORPHA:2762)
Progressive osseous heteroplasia (POH) is a rare genetic bone disorder characterized clinically by progressive extraskeletal bone formation presenting in early life with cutaneous ossification, that progressively involves subcutaneous and then subsequently deep connective tissues, including muscle and fascia. POH overlaps with a number of related genetic disorders including Albright hereditary osteodystrophy, pseudohypoparathyroidism (see these terms), and primary osteoma cutis, that share the common features of superficial heterotopic ossification in association with inactivating mutations of GNAS gene (20q13.2-q13.3), coding for guanine nucleotide-binding proteins. POH can, however, be distinguished clinically by the deep and progressive nature of the heterotopic bone formation.
Progressive polyneuropathy with bilateral striatal necrosis (ORPHA:217396)
Progressive polyneuropathy with bilateral striatal necrosis is a rare, genetic disorder of thiamine metabolism and transport characterized by the childhood-onset of recurrent episodes of flaccid paralysis and encephalopathy, associated with bilateral striatal necrosis and chronic progressive axonal polyneuropathy with proximal and distal muscle weakness, areflexia, contractures and foot deformities.
Progressive pseudorheumatoid arthropathy of childhood (ORPHA:1159)
A rare spondyloepiphyseal dysplasia (SED) characterized by an association with progressive arthropathy.
Epidemiology
The prevalence of progressive pseudorheumatoid arthropathy (dysplasia) of childhood (PPAC; PPD) has been estimated at 1/1,000,000.
Clinical description
Most patients present the disease before the age of 8 years (the onset varies between 2 and 11 years). Typically, there are no symptoms in the newborn period. The most common signs at diagnosis are progressive stiffness and swelling of small joints of hands (interphalangeal) without obvious signs of inflammation. Other joints are progressively affected: toes, elbows, writs, knees, ankles and spine. Bowing of the legs, motion range limitation, deformities and pain develop gradually, and spread to other joints. Many patients have spinal involvement manifesting as exaggerated lumbar lordosis, thoracic kyphosis, and/or scoliosis. Radiologically, the condition presents as SED (reduced joint space, abnormal and often large epiphyses and platyspondyly) with osteoporosis. Extraskeletal manifestations (besides those secondary to the bony changes) have not been reported. Patients have normal facial appearance and intelligence.
Etiology
The responsible gene CCN6 (mapping to human chromosome 6q22) encodes a secreted growth regulator.
Diagnostic methods
Diagnosis is based on clinical and radiographic findings. Molecular testing is available on research basis.
Differential diagnosis
PPAC can be initially misdiagnosed as juvenile idiopathic (rheumatoid) arthritis but is distinguished on radiographic analysis (especially the platyspondyly and generalised epiphyseal dysplasia) and the absence of inflammatory joint disease. PPAC must be differentiated from juvenile idiopathic arthritis to ensure optimal treatment and to avoid unnecessary exposure to immunosuppressants.
Antenatal diagnosis
Antenatal diagnosis is possible where the pathogenic variant has previously been identified in a family member.
Genetic counseling
Transmission is autosomal recessive. Genetic counseling should be offered to at-risk couples (both individuals are carriers of a disease-causing mutation) informing them that there is a 25% risk of having an affected child at each pregnancy.
Management and treatment
There is no specific treatment for PPAC. No clear prevention, improvement or slowing the disease course with anti-inflammatory drugs has been demonstrated.
Prognosis
PPAC does not affect life expectancy, but the progressive nature of the disease frequently requires joint replacement by early adulthood.

                            Last update: 
                            July 2024


                            - Expert reviewer(s): 
                            Pr Katta GIRISHA
Progressive retinal dystrophy due to retinol transport defect (ORPHA:352718)
Progressive retinal dystrophy due to retinol transport defect is a rare, genetic, metabolite absorption and transport disorder characterized by progressive rod-cone dystrophy, usually presenting with impaired night vision in childhood, progressive loss of visual acuity and severe retinol deficiency without keratomalacia. Association with ocular colobomas, severe acne and hypercholesterolemia has been reported.
Progressive scapulohumeroperoneal distal myopathy (ORPHA:447977)
A rare genetic muscular dystrophy characterized by progressive muscle weakness in a scapulo-humero-peroneal and distal distribution, featuring wrist extensor weakness, finger and foot drop, scapular winging, mild facial weakness, contractures of the Achilles tendon, elbow, and shoulder, and diminished or absent deep tendon reflexes. A predilection for the upper extremities has been reported in some patients. Respiratory muscles are spared until late in the disease course. Age of onset, progression, and severity of the disease vary significantly between individuals. Muscle biopsy shows groups of atrophic type I fibers and increased internal nuclei.
Progressive sensorineural hearing loss-hypertrophic cardiomyopathy syndrome (ORPHA:228012)
A rare disorder characterized by progressive, late onset, autosomal dominant sensorineural hearing loss, QT interval prolongation, and mild cardiac hypertrophy.
Progressive spondyloepimetaphyseal dysplasia-short stature-short fourth metatarsals-intellectual disability syndrome (ORPHA:457395)
A rare genetic multiple congenital anomalies/dysmorphic syndrome characterized by global developmental delay and intellectual disability, progressive spondyloepimetaphyseal dysplasia, short stature, short fourth metatarsals, and dysmorphic craniofacial features (including microcephaly, hypertelorism, epicanthal folds, mild ptosis, strabismus, malar hypoplasia, short nose, depressed nasal bridge, full lips, small, low-set ears, and short neck). Craniosynostosis, generalized hypotonia, as well as asymmetry of the cerebral hemispheres and mild thinning of the corpus callosum on brain imaging have also been described.