TaoMedAI/RareMedData huggingface dataset:
Autosomal recessive intermediate Charcot-Marie-Tooth disease type D (ORPHA:435998)
Autosomal recessive intermediate Charcot-Marie-Tooth disease type D is a rare hereditary motor and sensory neuropathy characterized by childhood onset of unsteady gait, pes cavus, frequent falls and foot dorsiflexor weakness slowly progressing to distal upper and lower limb muscle weakness and atrophy, distal sensory impairment and reduced tendon reflexes. Additional symptoms may include bilateral sensorineural hearing impairment and neuropathic pain.
Autosomal recessive isolated optic atrophy (ORPHA:98676)
A rare hereditary optic atrophy characterized by an early onset of bilateral optic nerve degeneration without other systemic features. Clinical manifestations include pallor of the optic disks, severe but slowly progressing visual impairment, and in some patients also paracentral scotoma, photophobia and dyschromatopsia.
Autosomal recessive Kenny-Caffey syndrome (ORPHA:93324)
A rare, primary bone dysplasia characterized by prenatal and postnatal growth retardation, short stature, cortical thickening and medullary stenosis of the long bones, absent diploic space in the skull bones, hypocalcemia due to the hypoparathyroidism, small hands and feet, delayed mental and motor development, intellectual disability, dental anomalies, and dysmorphic features, including prominent forehead, small deep-set eyes, beaked nose, and micrognathia.
Autosomal recessive lethal neonatal axonal sensorimotor polyneuropathy (ORPHA:538096)
A rare, genetic, autosomal recessive axonal hereditary motor and sensory neuropathy disease characterized by prenatal onset of a severe sensorimotor axonal polyneuropathy (reflected by reduced fetal movement and polyhydramnios), manifesting, at birth, with respiratory failure requiring mechanical ventilation, profound muscular hypotonia, rapidly progressing distal muscle weakness, and absent deep tendon reflexes, in the absence of contractures, leading to death before 8 months of age. Neuropathological findings show severe loss of large- and medium-sized myelinated fibers without signs of demyelination.
Autosomal recessive leukoencephalopathy-ischemic stroke-retinitis pigmentosa syndrome (ORPHA:314572)
A rare neurologic disease characterized by global developmental delay, intellectual disability, multiple ischemic lesions in brain MRI, behavioral abnormalities, dystonia, choreic movements and pyramidal syndrome, facial dysmorphism (hypertelorism, arched palate, macroglossia), retinitis pigmentosa, scoliosis, seizures.
Autosomal recessive lower motor neuron disease with childhood onset (ORPHA:206580)
A rare, genetic, neuromuscular disease characterized by proximal muscle weakness with an early involvement of foot and hand muscles following normal motor development in early childhood, a rapidly progressive disease course leading to generalized areflexic tetraplegia with contractures, severe scoliosis, hyperlordosis, and progressive respiratory insufficiency leading to assisted ventilation. Cranial nerve functions are normal and tongue wasting and fasciculations are absent. Milder phenotype with a moderate generalized weakness and slower disease progress was reported.
Autosomal recessive mendelian susceptibility to mycobacterial diseases due to a complete deficiency (ORPHA:319535)
A group of genetic variants of mendelian susceptibility to mycobacterial diseases (MSMD) comprised of MSMD due to complete interferon gamma receptor 1 (IFN-gammaR1) deficiency, complete IFN-gammaR2 deficiency, complete interleukin-12 subunit beta (IL12B) deficiency, complete interleukin-12 receptor subunit beta-1 (IL-12RB1) deficiency and complete ISG15 deficiency.
Epidemiology
The prevalence is unknown.
Clinical description
This group of diseases has extreme clinical variability ranging from relatively mild infections with bacillus Calmette-Guérin (BCG) and salmonellosis (in IL12B and IL-12RB1 deficiencies) to severe and often fatal infections with BCG and other environmental mycobacteria (complete IFN-gammaR1 and IFN-gammaR2 deficiencies).
Etiology
Autosomal recessive MSMD due to a complete deficiency is caused by mutations in one of 5 genes: IFNGR1, IFNGR2, IL12B , IL12RB1 and ISG15. Mutations in these genes impair IL-12 dependent IFN-gamma immunity.

                            Last update: 
                            February 2013


                            - Expert reviewer(s): 
                            Dr Jacinta BUSTAMANTE  - Pr Jean-Laurent CASANOVA
Autosomal recessive mendelian susceptibility to mycobacterial diseases due to a partial deficiency (ORPHA:319539)
A group of genetic variants of mendelian susceptibility to mycobacterial diseases (MSMD) due to autosomal recessive mutations in the IFNGR1 and IFNGR2 genes which lead to a residual response of IFN-gamma.
Epidemiology
The prevalence is unknown.
Clinical description
Infections in those with autosomal recessive MSMD due to a partial deficiency usually occur after the age of 3 to adulthood. Partial IFN-gammaR1 deficient patients experience infections that are more commonly due to localized non-tuberculosis mycobacterial (NTM) infections. They are also vulnerable to Mycobacterium tuberculosis. Infections in those with a partial IFN-gammaR2 deficiency are due to Mycobacterium bovis BCG and Mycobacterium abscessus. Manifestations include fever, weight loss, lymphadenopathy and hepatosplenomegaly. The infections are usually mild and, with treatment, patients remain in relatively good health.
Etiology
Autosomal recessive MSMD due to a partial deficiency is caused by mutations in either the IFNGR1 or IFNGR2 genes. These mutations lead to patients that have only a residual response to IFN-gamma and consequently have selective susceptibility to BCG and non-tuberculosis environmental mycobacteria (EM) infections and in rare cases to tuberculosis infections.

                            Last update: 
                            February 2013


                            - Expert reviewer(s): 
                            Dr Jacinta BUSTAMANTE  - Pr Jean-Laurent CASANOVA
Autosomal recessive mendelian susceptibility to mycobacterial diseases due to complete RORgamma receptor deficiency (ORPHA:477857)
A rare primary immunodeficiency characterized by increased susceptibility to infections with candida albicans and weakly pathogenic mycobacteria, such as mycobacterium bovis. Patients present in infancy with chronic mucocutaneous candidiasis of varying severity, disseminated mycobacterial disease, absence of palpable axillary and cervical lymph nodes, reduced thymus size, and variable hepatosplenomegaly. The immunological phenotype comprises mild T-cell lymphopenia, absence of type 1 natural killer T-cells and mucosal-associated invariant T-cells, and low levels of type 3 innate lymphoid cells.
Autosomal recessive mendelian susceptibility to mycobacterial diseases due to partial IFNgammaR1 deficiency (ORPHA:319569)
A genetic variant of mendelian susceptibility to mycobacterial diseases (MSMD) characterized by a partial deficiency in IFN-gammaR1, leading to a residual response to IFN-gamma and, consequently, to recurrent, moderately severe infections with bacillus Calmette-Guérin (BCG) and other environmental mycobacteria (EM).
Epidemiology
The prevalence is unknown. The same homozygous mutations have been reported in 14 patients in 11 kindreds from Poland, Portugal, Spain and Chile, thus reflecting a founder effect.
Clinical description
Patients present with moderately severe mycobacterial infections, BCG or EM diseases. These infections are recurrent but less severe than those seen in MSMD due to complete IFN-gammaR1 and IFN-gammaR2 deficiencies (see these terms). Infections with Mycobacterium tuberculosis have also been reported in patients with this disorder.
Etiology
Autosomal recessive MSMD due to partial IFN-gammaR1 deficiency is caused by homozygous mutations in the IFNGR1 gene on chromosome 6q23-q24 that encodes the IFN-gamma receptor ligand binding chain. The most common mutation is, by far, I87T. This mutation leads to the expression of IFN-gamma receptors on the cell surface with no signal transduction capacity and they therefore only show a partial response to IFN-gamma.
Diagnostic methods
Diagnosis is made by laboratory analysis. Low production of IL12p40 is detected in blood after BCG and BCG+IFN-gamma activation. Cells of patients show a residual response to IFN-gamma in terms of Stat-1 DNA-binding (GAS-binding activity) and HLA-II induction. A mutational analysis will identify a mutation in the IFNGR1 gene. Low levels of IFN-gamma were detected in the serum of the patients.
Differential diagnosis
Other genetic etiologies of MSMD should be excluded.
Antenatal diagnosis
This immunodeficiency is not severe and antenatal diagnosis is not necessary.
Genetic counseling
Transmission is autosomal recessive and genetic counseling is possible.
Management and treatment
BCG vaccinations should be avoided in those with a known mutation in IFNGR1. Patients should be treated with antibiotics and, if necessary, with recombinant IFN-gamma.
Prognosis
Prognosis is usually good.

                            Last update: 
                            February 2013


                            - Expert reviewer(s): 
                            Dr Jacinta BUSTAMANTE  - Pr Jean-Laurent CASANOVA
Autosomal recessive mendelian susceptibility to mycobacterial diseases due to partial IFNgammaR2 deficiency (ORPHA:319574)
Autosomal recessive mendelian susceptibility to mycobacterial diseases (MSMD) due to partial IFNgammaR2 deficiency is a genetic variant of MSMD (see this term) characterized by a partial deficiency in IFN-gammaR2, leading to a residual response to IFN-gamma and consequently to recurrent, moderately severe infections with bacillus Calmette-Guérin (BCG) and other environmental mycobacteria (EM).
Epidemiology
The prevalence is unknown. Only one patient has been reported with this variant to date.
Clinical description
The patient presented with a mild infection caused by BCG and M. abscessus.
Etiology
Autosomal recessive MSMD due to partial IFNgammaR2 deficiency is caused by a homozygous mutation (R114C) in IFNGR2 on chromosome 21q22.1-22.2 that encodes the IFN-gamma receptor ligand binding chain. This mutation leads to a residual cellular response to IFN-gamma in terms of IL12p40 production.
Genetic counseling
Transmission is autosomal recessive and genetic counseling is possible.

                            Last update: 
                            February 2013


                            - Expert reviewer(s): 
                            Dr Jacinta BUSTAMANTE  - Pr Jean-Laurent CASANOVA
Autosomal recessive mendelian susceptibility to mycobacterial diseases due to partial JAK1 deficiency (ORPHA:574957)
A rare primary immunodeficiency characterized by recurrent atypical mycobacterial infections, accompanied by relatively minor viral infections, on an immunological background of reduced induction of expression of interferon-regulated genes and dysregulated cytokine production, as revealed by laboratory studies. Global developmental delay and occurrence of non-hematopoietic malignancy at a young age have been reported in association.
Autosomal recessive multiple pterygium syndrome (ORPHA:2990)
A rare genetic multiple congenital anomalies/dysmorphic syndrome characterized by congenital pterygia (webbing) mainly affecting the neck and large joints, arthrogryposis multiplex, short stature, and craniofacial dysmorphism (including ptosis, downslanting palpebral fissures, high-arched palate, and retrognathia). Additional manifestations are decreased movements, facial weakness, respiratory distress, vertebral anomalies, scoliosis, anomalies of the fingers, and cryptorchidism, among others. The disease is a non-lethal variant of multiple pterygium syndrome.
Autosomal recessive myogenic arthrogryposis multiplex congenita (ORPHA:319332)
Autosomal recessive myogenic arthrogryposis multiplex congenita is a rare inherited neuromuscular disease characterized by prenatal presentation (usually in the second trimester) of reduced fetal movements and abnormal positioning resulting in joint abnormalities that may involve both lower and upper extremities and is usually symmetric, severe hypotonia at birth with bilateral club foot, motor development delay, mild facial weakness without opthalmoplegia, absent deep tendon reflexes, normal motor and sensory nerve conduction velocities, no cerebellar or pyramidal involvement, and progressive disease course with loss of ambulation after the first decade of life.
Autosomal recessive nail dysplasia (ORPHA:280654)
A rare, isolated nail anomaly characterized by claw-shaped, thick, hyperplastic, hard and hyperpigmented nails, subungual hyperkeratosis, onycholysis and slow nail growth. Variable degree of disease severity has been reported.
Autosomal recessive optic atrophy, OPA7 type (ORPHA:227976)
A rare, syndromic, hereditary optic neuropathy disorder characterized by early-onset, severe, progressive visual impairment, optic disc pallor and central scotoma, variably associated with dyschromatopsia, auditory neuropathy (e.g. mild progressive sensorineural hearing loss), sensorimotor axonal neuropathy and, occasionally, moderate hypertrophic cardiomyopathy.
Autosomal recessive palmoplantar keratoderma and congenital alopecia (ORPHA:1366)
Autosomal recessive palmoplantar hyperkeratosis and congenital alopecia (PPK-CA) is a rare genetic skin disorder characterized by congenital alopecia and palmoplantar hyperkeratosis. It is usually associated with cataracts, progressive sclerodactyly and pseudo-ainhum.
Epidemiology
To date, autosomal recessive PPK-CA has been reported in two families (seven affected individuals). An additional sporadic patient was likely affected by the same condition.
Clinical description
Similarly to the dominant variant, autosomal recessive PPK-CA usually presents during infancy. Its very early onset is often characterized by fading of facial, scalp and body hair within the first months of life without subsequent re-growth. Body and facial keratosis pilaris are additional features which appear in the following years. Skin thickening of palms and soles develops during infancy and may have an unusual pattern affecting the two sides of fingers and palms, but usually sparing the palmar surfaces. Periungueal involvement is typical and leads to secondary nail dystrophy. Autosomal recessive PPK-CA shows a relatively more severe evolution compared to the dominant variant as many patients develop sclerodactyly, small joint contractures and pseudo-ainhum. The original family also had congenital cataract.
Etiology
The genetic basis of autosomal recessive PPK-CA is unknown.
Differential diagnosis
Palmoplantar keratoderma and congenital alopecia/hypotrichosis is also found in ectodermal dysplasias and keratinization disorders, including hydrotic ectodermal dysplasia; hypotrichosis-osteolysis-periodontitis-palmoplantar keratoderma yndrome; KID syndrome; odonto-onycho-dermal dysplasia; Lelis syndrome; mutilating palmoplantar keratoderma with periorificial keratotic plaques; and Schöpf-Schulz-Passarge syndrome.
Genetic counseling
Transmission appears to be autosomal recessive.

                            Last update: 
                            July 2013


                            - Expert reviewer(s): 
                            Dr Marco CASTORI
Autosomal recessive primary immunodeficiency with defective spontaneous natural killer cell cytotoxicity (ORPHA:437552)
A rare, genetic primary immunodeficiency characterized by recurrent respiratory and skin viral infections (Epstein-Barr virus, herpes simplex virus, human papillomavirus), deficient spontaneous cytotoxicity of natural killer cells, but preserved antibody-dependent cellular cytotoxicity. No other abnormalities are present on immunologic work-up.
Autosomal recessive progressive external ophthalmoplegia (ORPHA:254886)
A rare genetic, neuro-ophthalmological disease characterized by progressive weakness of the external eye muscles, resulting in bilateral ptosis and diffuse, symmetric ophthalmoparesis. Additional signs may include generalized skeletal muscle weakness, muscle atrophy, sensory axonal neuropathy, ataxia, cardiomyopathy, and psychiatric symptoms. It is usually more severe than autosomal dominant form.
Autosomal recessive proximal renal tubular acidosis (ORPHA:93607)
A rare autosomal recessive form of proximal renal tubular acidosis characterized by an isolated defect in the proximal tubule leading to the decreased reabsorption of bicarbonate and consequentially to urinary bicarbonate wastage. Presentation is typically with hyperchloremic acidosis, usually occurring in childhood. Extrarenal manifestations include ocular abnormalities (band keratopathy, glaucoma, and cataracts), intellectual disability and severe growth retardation. Other features like dental enamel defects, basal ganglia calcification and pancreatitis are sometimes present.
Autosomal recessive Robinow syndrome (ORPHA:1507)
Autosomal recessive Robinow syndrome (RRS) is the less common type of Robinow syndrome (RS, see this term) characterized by short-limb dwarfism, costovertebral segmentation defects and abnormalities of the head, face and external genitalia.
Epidemiology
Fewer than 100 cases of this type have been reported in the literature to date.
Clinical description
The disorder is usually recognizable at birth or in early childhood. The clinical signs are generally far more severe in recessive cases of RS than in the dominant form, particularly skeletal abnormalities. All patients with the recessive form of RS suffer from vertebral segmentation abnormalities, resulting in scoliosis and chest deformities. Rib fusions are considered to be characteristic of the autosomal recessive form.
Etiology
The syndrome is caused by mutations in the ROR2 gene (9q22).
Genetic counseling
Transmission is autosomal recessive.

                            Last update: 
                            May 2011


                            - Expert reviewer(s): 
                            Dr Juliana MAZZEU
Autosomal recessive secondary polycythemia not associated with VHL gene (ORPHA:247378)
A rare, hereditary, hematologic disease characterized by an increase in hemoglobin, hematocrit and erythrocyte mass resulting in plethora or ruddy complexion, headache, dizziness, tinnitus and exertional dyspnea. In some cases, thrombophlebitis and arthralgia have also been reported.
Autosomal recessive severe congenital neutropenia due to CSF3R deficiency (ORPHA:420702)
A rare, genetic, primary immunodeficiency disorder characterized by predisposition to recurrent, life-threatening bacterial infections associated with decreased peripheral neutrophil granulocytes (absolute neutrophil count less than 500 cells/microliter), resulting from recessively inherited loss-of-function mutations in the CSF3R gene. Full maturation of all three lineages in the bone marrow and refractoriness to in vivo rhG-CSF treatment are associated.
Autosomal recessive severe congenital neutropenia due to CXCR2 deficiency (ORPHA:420699)
A rare, genetic, primary immunodeficiency disorder characterized by recurrent bacterial infections (including septic thrombophlebitis and subacute bacterial endocarditis) and neutropenia without lymphopenia or warts, resulting from recessively inherited mutations in CXCR2.
Autosomal recessive spastic ataxia with leukoencephalopathy (ORPHA:314603)
A rare, genetic, autosomal recessive spastic ataxia disease characterized by cerebellar ataxia, spasticity, cerebellar (and in some cases cerebral) atrophy, dystonia, and leukoencephalopathy.
Autosomal recessive spastic ataxia-optic atrophy-dysarthria syndrome (ORPHA:254343)
A rare, genetic, autosomal recessive spastic ataxia disease characterized by onset in early childhood of spastic paraparesis, cerebellar ataxia, dysarthria and optic atrophy.
Autosomal recessive spastic paraplegia type 11 (ORPHA:2822)
A complex hereditary spastic paraplegia characterized by progressive lower limbs weakness and spasticity, upper limbs weakness, dysarthria, hypomimia, sphincter disturbances, peripheral neuropathy, learning difficulties, cognitive impairment and dementia. Magnetic resonance imaging shows thin corpus callosum, cerebral atrophy, and periventricular white matter changes.
Autosomal recessive spastic paraplegia type 14 (ORPHA:100995)
Autosomal recessive spastic paraplegia type 14 is a rare, complex hereditary spastic paraplegia characterized by adulthood-onset of slowly progressive spastic paraplegia of lower limbs presenting with spastic gait, hyperreflexia, and mild lower limb hypertonicity associated with mild intellectual disability, visual agnosia, short and long-term memory deficiency and mild distal motor neuropathy. Bilateral pes cavus and extensor plantar responses are also associated.
Autosomal recessive spastic paraplegia type 15 (ORPHA:100996)
Autosomal recessive spastic paraplegia type 15 is a complex form of hereditary spastic paraplegia characterized by a childhood to adulthood onset of slowly progressive lower limb spasticity (resulting in gait disturbance, extensor plantar responses and decreased vibration sense) associated with mild intellectual disability, mild cerebellar ataxia, peripheral neuropathy (with distal upper limb amyotrophy) and retinal degeneration. Thin corpus callosum is a common imaging finding.
Autosomal recessive spastic paraplegia type 20 (ORPHA:101000)
Autosomal recessive spastic paraplegia type 20 (SPG20) is a type of complex hereditary spastic paraplegia characterized by an onset in infancy of progressive spastic paraparesis associated with distal amyotrophy, psuedobulbar palsy, motor and cognitive delays, mild cerebellar signs (dysarthria, dysdiadochokinesia, mild intention tremor), short stature and subtle skeletal abnormalities (pes cavus, mild talipes equinovarus, kyphoscoliosis). SPG20 is due to mutations in the SPG20 gene (13q13.1), which encodes the protein spartin.
Autosomal recessive spastic paraplegia type 21 (ORPHA:101001)
Autosomal recessive spastic paraplegia type 21 is a complex type of hereditary spastic paraplegia characterized by an onset in adolescence or adulthood of slowly progressive spastic paraparesis associated with the additional manifestations of apraxia, cognitive and speech decline (leading to dementia and akinetic mutism in some cases), personality disturbances and extrapyramidal (e.g. oromandibular dyskinesia, rigidity) and cerebellar (i.e. dysdiadochokinesia and incoordination) signs. Subtle abnormalities (e.g. developmental delays) may be noted earlier in childhood. A thin corpus callosum and white matter abnormalities are equally reported on magnetic resonance imaging.
Autosomal recessive spastic paraplegia type 23 (ORPHA:101003)
Autosomal recessive spastic paraplegia type 23 (SPG23) is a rare, complex type of hereditary spastic paraplegia that presents in childhood with progressive spastic paraplegia, associated with peripheral neuropathy, skin pigment abnormalities (i.e. vitiligo, hyperpigmentation, diffuse lentigines), premature graying of hair, and characteristic facies (i.e. thin with ''sharp'' features). The SPG23 phenotype has been mapped to a locus on chromosome 1q24-q32.
Autosomal recessive spastic paraplegia type 24 (ORPHA:101004)
A very rare, pure form of spastic paraplegia characterized by an onset in infancy of lower limb spasticity associated with gait disturbances, scissor gait, tiptoe walking, clonus and increased deep tendon reflexes. Mild upper limb involvement may occasionally also be associated.
Autosomal recessive spastic paraplegia type 25 (ORPHA:101005)
Autosomal recessive spastic paraplegia type 25 (SPG25) is a rare, complex type of hereditary spastic paraplegia characterized by adult-onset spastic paraplegia associated with spinal pain that radiates to the upper or lower limbs and is related to disk herniation (with minor spondylosis), as well as mild sensorimotor neuropathy. The SPG25 phenotype has been mapped to a locus on chromosome 6q23-q24.1.