TaoMedAI/RareMedData huggingface dataset:
X-linked intellectual disability-dysmorphism-cerebral atrophy syndrome (ORPHA:2958)
An X-linked syndromic intellectual disability characterized by intellectual disability, subcortical cerebral atrophy, dental anomalies, patella luxation, lower back skin dimple, and dysmorphic facial features.
X-linked intellectual disability-epilepsy-progressive joint contractures-dysmorphism syndrome (ORPHA:85319)
X-linked intellectual disability-epilepsy-progressive joint contractures-dysmorphism syndrome is characterised by intellectual deficit, epilepsy, facial dysmorphism and progressive joint contractures. It has been described in two boys. Hypotonia and feeding problems at birth were also reported. The mode of transmission is X-linked.
X-linked intellectual disability-global development delay-facial dysmorphism-sacral caudal remnant syndrome (ORPHA:480907)
A rare multiple congenital anomalies/dysmorphic syndrome characterized by global developmental delay, intellectual disability, growth retardation, hearing impairment, characteristic facial dysmorphology (including prominent supraorbital ridges, downslanting palpebral fissures, deep-set eyes, long face, sagging cheeks, anteverted nares, and pointed chin), generalized hypotonia, joint hypermobility, gluteal crease with sacral caudal remnant and sacral dimple, and variable neurological features. Various ophthalmic, cutaneous, musculoskeletal, gastrointestinal, and cardiovascular anomalies have also been described.
Epidemiology
Due to the small number of known affected individuals, the prevalence of this condition remains unknown. Globally, some 30 cases are known.
Clinical description
The main clinical features include growth retardation, delayed speech and language development, delayed gross motor development, generalized hypotonia, intellectual disability and symptoms of autism spectrum disorder. Microcephaly, facial dysmorphism, hearing impairment, variable brain morphological abnormalities, and congenital heart defects, hypospadias and cryptorchidism have also been reported.
Etiology
The disorder is caused by pathogenic mutations in the TAF1 gene (Xq13.1). The encoded protein, transcription initiation factor TFIID subunit 1, is a part of the transcription factor II D complex that participates in the initiation of the transcription of RNA polymerase II transcription-dependent genes.
Diagnostic methods
Diagnosis is based on clinical examination and genetic testing.
Differential diagnosis
The main differential diagnosis options include other X-linked intellectual disability syndromes that involve similar symptoms or clinical findings.
Antenatal diagnosis
Antenatal diagnosis is possible if a familial pathogenic variant has been identified.
Genetic counseling
The pattern of inheritance is X-linked. Where the female is a carrier, at risk couples should be informed that for each pregnancy the male offspring have a 50% risk of being affected and female offspring have a 50% risk of being a carrier. Females may rarely be affected due to skewed X chromosome inactivation.
Management and treatment
Management is symptomatic. After initial diagnosis, evaluation by a pediatric urologist, pediatric cardiologist, pediatric neurologist, otorhinolaryngologist or other relevant specialist may be warranted to rule out associated congenital abnormalities.
Prognosis
Studies suggest that the symptoms are generally not progressive; however, individual cases with progressive symptomatology have been reported. Longitudinal data regarding life expectancy is currently unavailable due to the small number of known cases.

                            Last update: 
                            October 2021


                            - Expert reviewer(s): 
                            Dr Outi KUISMIN | ITHACA* - Dr Leila SOIKKONEN | ITHACA*


                                * European Reference Network
X-linked intellectual disability-hypogammaglobulinemia-progressive neurological deterioration syndrome (ORPHA:85317)
A rare genetic multiple congenital anomalies/dysmorphic syndrome characterized by moderate intellectual disability, dysmorphic facial features (such as prominent glabella, synophrys, and prognathism), generalized hirsutism, bilateral single palmar creases, and seizures. Additional reported manifestations include slowly progressive neurological deterioration with muscular weakness and impaired gait and balance, as well as hypogammaglobulinemia with specific absence of plasma and/or secretory IgA, among others. Brain imaging may show mild cerebellar atrophy and thin corpus callosum.
X-linked intellectual disability-hypogonadism-ichthyosis-obesity-short stature syndrome (ORPHA:3055)
X-linked intellectual disability-hypogonadism-ichthyosis-obesity-short stature syndrome is a rare X-linked intellectual disability syndrome characterized by intellectual disability associated with short stature, obesity, primary hypogonadism and an ichthyosiform skin condition. There have been no further descriptions in the literature since 1982.
X-linked intellectual disability-hypotonia-facial dysmorphism-aggressive behavior syndrome (ORPHA:85329)
A rare X-linked syndromic intellectual disability characterized by severe to profound intellectual disability, muscular hypotonia in childhood, delayed walking, delayed or minimal/absent speech, behavioral abnormalities including aggressiveness, agitation, and self-injurious behavior, and dysmorphic facial features (such as triangular face with high forehead, prominent ears, and small, pointed chin). Additional reported manifestations include microcephaly, short stature, and seizures, among others.
X-linked intellectual disability-hypotonia-movement disorder syndrome (ORPHA:457260)
A rare, genetic, syndromic intellectual disability characterized by mild to severe intellectual disability associated with variable features, including hypotonia, dyskinesia, spasticity, wide-based gait, microcephaly, epilepsy and behavioral problems. MRI imaging may show a corpus callosum hypoplasia or ventricular enlargement. Other variable features, such as joint hyperlaxity, skin pigmentary abnormalities, and visual impairment, have also been reported.
X-linked intellectual disability-limb spasticity-retinal dystrophy-arginine vasopressin deficiency (ORPHA:423479)
X-linked intellectual disability-limb spasticity-retinal dystrophy-diabetes insipidus syndrome is a rare genetic neurometabolic disease characterized by severe intellectual disability, spastic quadraparesis, Leber´s congenital amaurosis and diabetes insipidus. Additional manifestations include facial dysmorphy (dolichocephalic skull, hypertelorism, deep-set eyes, hypoplastic nares, low-set ears), short stature, truncal hypotonia and axial hypertonia. Brain anomalies (e.g. thin corpus callosum with lack of isthmus and tapered splenium, hypoplasia or atrophy of the optic chiasm, prominent lateral ventricles, diminished white matter), described on magnetic resonance imaging, have been reported. High prenatal α-fetoprotein and intrauterine growth restriction is observed in routine pregnancy examination.
X-linked intellectual disability-macrocephaly-macroorchidism syndrome (ORPHA:85320)
An X-linked syndromic intellectual disability characterized by intellectual disability, macrocephaly, macroorchidism, prominent eyebrows and jaws and abnormal ears. Males are predominantly affected, some females show lower cognitive abilities.
X-linked intellectual disability-plagiocephaly syndrome (ORPHA:2898)
A rare, syndromic intellectual disability characterized by severe intellectual deficit, brachycephaly, plagiocephaly, and prominent forehead in male patients. Females may display moderate intellectual deficit without craniofacial dysmorphism. There have been no further descriptions in the literature since 1992.
X-linked intellectual disability-psychosis-macroorchidism syndrome (ORPHA:3077)
An X-linked syndromic intellectual disability characterized by developmental delay, variable degree of intellectual disability, speech delay or absent speech, pyramidal signs, tremor, macroorchidism and variable mood and behavior problems, including psychosis and autistic-like behavior. Males are predominantly affected, some females show lower cognitive abilities.
X-linked intellectual disability-retinitis pigmentosa syndrome (ORPHA:85332)
X-linked intellectual disability-retinitis pigmentosa syndrome is characterized by moderate intellectual deficit and severe, early-onset retinitis pigmentosa. It has been described in five males spanning three generations of one family. Some patients also had microcephaly. It is transmitted as an X-linked recessive trait.
X-linked intellectual disability-seizures-psoriasis syndrome (ORPHA:3052)
A rare, X-linked syndromic intellectual disability disorder characterized by severe intellectual disability, psychomotor developmental delay, generalized seizures, and psoriasis. Mild craniofacial dysmorphism, such as hypertelorism, broad nasal bridge, anteverted nares, macrostomia, highly arched palate and large ears, is also associated. There have been no further descriptions in the literature since 1988.
X-linked intellectual disability-short stature-overweight syndrome (ORPHA:457240)
X-linked intellectual disability-short stature-overweight syndrome is a multiple congenital anomalies syndrome characterized by borderline to severe intellectual disability, speech delay, short stature, elevated body mass index, a pattern of truncal obesity (reported in older males), and variable neurologic features (e.g. hypotonia, tremors, gait disturbances, behavioral problems, and seizure disorders). Less common manifestations include microcephaly, microorchidism and/or microphallus. Dysmorphic features have been reported in some patients but no consitent pattern has been noted.
X-linked keloid scarring-reduced joint mobility-increased optic cup-to-disc ratio syndrome (ORPHA:482606)
A rare genetic disease characterized by congenital contractures of the distal interphalangeal joints, progressive stiffness of the shoulders and neck, keloid scarring, increased optic cup-to-disc ratio, and renal stones. Additional reported features include arthritis, osteoporosis, hypoplastic flexion creases, clinodactyly, anxiety, and facial dysmorphism (such as sloping forehead, prominent supraorbital ridges, downslanting palpebral fissures, prominent ears, and high arched palate). Female carriers exhibit a variable, milder phenotype.
X-linked lethal multiple pterygium syndrome (ORPHA:79447)
X-linked lethal multiple pterygium syndrome is a rare, genetic, developmental defect during embryogenesis characterized by the typical lethal multiple pterygium syndrome presentation (comprising of multiple pterygia, severe arthrogryposis, cleft palate, cystic hygromata and/or fetal hydrops, skeletal abnormalities and fetal death in the 2nd or 3rd trimester) with an X-linked pattern of inheritance.
X-linked lissencephaly with abnormal genitalia (ORPHA:452)
A rare genetic multiple congenital anomalies/dysmorphic syndrome characterized by lissencephaly, agenesis of the corpus callosum and other cerebral structural anomalies, early-onset intractable seizures, and ambiguous genitalia. Consequences of hypothalamic dysfunction, such as disturbed temperature regulation, may be observed. Additional anomalies including dysmorphic craniofacial features have been reported. The disease is fatal in infancy or childhood in males, while female carriers may be unaffected or show a milder phenotype with developmental delay, behavioral abnormalities, and seizures.
X-linked lymphoproliferative disease due to SAP deficiency (ORPHA:538931)
A rare, genetic, primary immunodeficiency disorder characterized by an abnormal immune response to Epstein-Barr virus (EBV) infection, caused by hemizygous mutations in the X-linked SH2D1A gene, resulting in B cell lymphoproliferation and manifesting with various phenotypes which include EBV-driven severe or fulminant mononucleosis, hemophagocytic lymphohistiocytosis (presenting with fulminant hepatitis, hepatic necrosis, bone marrow hypoplasia, and neurological involvement), hypogammaglobulinemia, and B-cell lymphoma. Additional variable manifestations include vasculitis, lymphomatoid granulomatosis, aplastic anemia, and chronic gastritis. Occasionally, T-cell lymphoma may be observed. Laboratory findings include normal or increased activated T cells and reduced memory B cells.
X-linked lymphoproliferative disease due to XIAP deficiency (ORPHA:538934)
A rare, genetic, primary immunodeficiency disorder characterized by an abnormal immune response to Epstein-Barr virus (EBV) infection, caused by hemizygous mutations in the X-linked XIAP gene, resulting in B cell lymphoproliferation and manifestating with various phenotypes which include EBV-driven hemophagocytic lymphohistiocytosis, hypogammaglobulinemia, recurrent splenomegaly, hepatitis, colitis, and intestinal bowel disease with features of Crohn's disease. Additional manifestations include variable auto-inflammatory symptoms such as uveitis, arthritis, skin abscesses, erythema nodosum, and nephritis. Neurological involvement is rare and lymphoma is never observed. Laboratory findings include normal or increased activated T cells, low or normal iNKT cells, and normal or reduced memory B cells.
X-linked mandibulofacial dysostosis (ORPHA:1131)
X-linked mandibulofacial dysostosis is an extremely rare multiple congenital abnormality syndrome that is characterized by microcephaly, malar hypoplasia with downslanting palpebral fissures, highly arched palate, apparently low-set and protruding ears, micrognathia, short stature, bilateral hearing loss, and learning disability. Occasionally, additional features have been observed such as bilateral cryptorchidism, cardiac valvular lesions, body asymmetry, and pectus excavatum.
X-linked microcephaly-growth retardation-prognathism-cryptorchidism syndrome (ORPHA:435938)
X-linked microcephaly-growth retardation-prognathism-cryptorchidism syndrome is a rare syndromic intellectual disability characterized by hypotonia, microcephaly, severe developmental delay, seizures, intellectual disability, growth retardation, cardiac septal defects, cryptorchidism, hypospadias, and dysmorphic features - prominent ears, prognathism, thin upper lip, dental crowding.
X-linked myopathy with excessive autophagy (ORPHA:25980)
X-linked myopathy with excessive autophagy is a childhood-onset X-linked myopathy characterised by slow progression of muscle weakness and unique histopathological findings.
Epidemiology
It has been described in about fifteen families.
Clinical description
The first manifestations appear typically in children around 5-10 years of age and include difficulty climbing stairs and running.
Etiology
The Xq28 locus has been associated with the disease.
Diagnostic methods
Muscle fibres are not necrotic but they show excessive autophagic activity and exocytosis of the phagocytosed material.
Genetic counseling
Transmission is X-linked recessive; female carriers are asymptomatic or only mildly affected.
Prognosis
Progression is very slow, longevity is not altered. Many patients need a wheelchair in their 6th decade of life.

                            Last update: 
                            June 2006
X-linked myopathy with postural muscle atrophy (ORPHA:178461)
A rare progressive muscular dystrophy characterized by an adult-onset scapulo-axio-peroneal myopathy. Clinical presentation includes shoulder girdle atrophy, scapular winging, axial muscular atrophy of postural muscles combined with a generalized hypertrophy. Typically, neck rigidity, rigid spine, Achilles tendon shortening, and respiratory insufficiency later in disease course are present.
X-linked myotubular myopathy-abnormal genitalia syndrome (ORPHA:456328)
X-linked myotubular myopathy-abnormal genitalia syndrome is a rare chromosomal anomaly, partial deletion of the long arm of chromosome X, characterized by a combination of clinical manifestations of X-linked myotubular myopathy and a 46,XY disorder of sex development. Patients present with severe form of congenital myopathy and abnormal male genitalia.
X-linked neurodegenerative syndrome, Bertini type (ORPHA:85334)
An X-linked syndromic intellectual disability characterized by congenital ataxia and generalized hypotonia, global developmental delay with intellectual disability, myoclonic encephalopathy, progressive neurological deterioration, macular degeneration, and recurrent bronchopulmonary infections.
X-linked neurodegenerative syndrome, Hamel type (ORPHA:85336)
An X-linked syndromic intellectual disability characterized by a few months of normal development, followed by progressive neurodegenerative course with gradual loss of vision, development of spastic tetraplegia, convulsions, microcephaly, failure to thrive, and early death.
X-linked non progressive cerebellar ataxia (ORPHA:314978)
X-linked non progressive cerebellar ataxia is a rare hereditary ataxia characterized by delayed early motor development, severe neonatal hypotonia, non-progressive ataxia and slow eye movements, presenting normal cognitive abilities and absence of pyramidal signs. Frequently patients also manifest intention tremor, mild dysphagia, and dysarthria. Brain MRI reveals global cerebellar atrophy with absence of other malformations or degenerations of the central and peripheral nervous systems.
X-linked osteoporosis with fractures (ORPHA:391330)
A rare, genetic, primary bone dysplasia with decreased bone density disorder characterized by childhood-onset osteoporosis associated with recurrent, multiple, osteoporotic, long bone fractures and/or vertebral compression fractures, significant height loss in adulthood, low bone mineral density scores, and otherwise no other abnormalities. Heterozygote females may be unaffected or have a milder phenotype.
X-linked parkinsonism-spasticity syndrome (ORPHA:363654)
A rare, genetic, neurological disorder characterized by parkinsonian features (including resting or action tremor, cogwheel rigidity, hypomimia and bradykinesia) associated with variably penetrant spasticity, hyperactive deep tendon reflexes and Babinski sign.
X-linked progressive cerebellar ataxia (ORPHA:1175)
A rare X-linked cerebellar ataxia, characterized by a combination of upper and lower motor neuron signs, with an age of onset in the first or second decade, slow progression, and normal intelligence. Typical features of cerebellar dysfunction include gait and limb ataxia, intention tremor, dysmetria, dysdiadochokinesia, dysarthria, nystagmus, and hyperreflexia. Further phenotypic features are pes cavus, scoliosis, muscle atrophy, and peripheral sensory and motor nerve abnormalities.
X-linked reticulate pigmentary disorder (ORPHA:85453)
X-linked reticulate pigmentary disorder is an extremely rare skin disease described in only four families to date and characterized in males by diffuse reticulate brown hyperpigmentated skin lesions developing in early childhood and a variety of systemic manifestations (recurrent pneumonia, corneal opacification, gastrointestinal inflammation, urethral stricture, failure to thrive, hypohidrosis, digital clubbing, and unruly hair and flared eyebrows), while in females, there is only cutaneous involvement with the development in early childhood of localized brown hyperpigmented skin lesions following the lines of Blaschko. This disease was first considered as a cutaneous amyloidosis, but amyloid deposits are an inconstant feature.
X-linked retinal dysplasia (ORPHA:1852)
A rare genetic eye disease characterized by abnormal proliferation of retinal tissue resulting in the formation of retinal folds, thereby causing gliosis and, clinically, variable degrees of visual impairment. No clinical findings other than those associated with the eyes have been demonstrated.
X-linked scapuloperoneal muscular dystrophy (ORPHA:431272)
A rare, genetic, muscular dystrophy disease characterized by the co-occurrence of late onset scapular and peroneal muscle weakness, principally manifesting with distal lower limb and proximal upper limb weakness and scapular winging.
X-linked severe congenital neutropenia (ORPHA:86788)
X-linked severe congenital neutropenia is an immunodeficiency syndrome characterized by recurrent major bacterial infections, severe congenital neutropenia, and monocytopenia. It has been described in five males spanning three generations of one family. It is transmitted as an X-linked recessive trait and is caused by mutations in the WAS gene, encoding the WASP protein.
X-linked skeletal dysplasia-intellectual disability syndrome (ORPHA:1436)
A rare genetic syndrome characterized by skeletal anomalies, including short stature, ridging of the metopic suture, a fusion of cervical vertebrae, thoracic hemivertebrae, scoliosis, sacral hypoplasia, short middle phalanges. Patients also had a moderate intellectual disability and abducens palsies. Glucose intolerance and imperforate anus were also described.
X-linked spastic paraplegia type 16 (ORPHA:100997)
A complex, hereditary, spastic paraplegia characterized by delayed motor development, spasticity, and inability to walk, later progressing to quadriplegia, motor aphasia, bowel and bladder dysfunction. Patients also present with vision problems and mild intellectual disability. The disease affects only males.
X-linked spastic paraplegia type 34 (ORPHA:171607)
X-linked spastic paraplegia type 34 is a pure form of hereditary spastic paraplegia characterized by late childhood- to early adulthood-onset of slowly progressive spastic paraplegia with spastic gait and lower limb hyperreflexia, brisk tendon reflexes and ankle clonus. Lower limb pain and reduced lower limb vibratory sense is also reported in some older adult patients.
X-linked spasticity-intellectual disability-epilepsy syndrome (ORPHA:3175)
A rare ARX-related epileptic encephalopathy characterized by infantile onset of myoclonic epilepsy with generalized spasticity, severe global developmental delay, and moderate to profound intellectual disability. Obligate female carriers show subtle, generalized hyperreflexia. Late onset progressive spastic ataxia has also been reported.
X-linked spinocerebellar ataxia type 3 (ORPHA:85297)
X-linked spinocerebellar ataxia type 3 is a form of spinocerebellar degeneration characterized by onset in infancy of hypotonia, ataxia, sensorineural deafness, developmental delay, esotropia, and optic atrophy, and by a progressive course leading to death in childhood. It has been described one family with at least six affected males from five different sibships (connected through carrier females). It is transmitted as an X-linked recessive trait.
X-linked spinocerebellar ataxia type 4 (ORPHA:85292)
A rare X-linked spinocerebellar ataxia characterized by ataxia, pyramidal tract signs and adult-onset dementia. The disease manifests during early childhood with delayed walking and tremor. The pyramidal signs appear progressively and by adulthood memory problems and dementia gradually become apparent.
X-linked spondyloepimetaphyseal dysplasia (ORPHA:93349)
A rare, genetic primary bone dysplasia disorder characterized by disproportionate short stature with mesomelic short limbs, leg bowing, lumbar lordosis, brachydactyly, joint laxity and a waddling gait. Radiographs show platyspondyly with central protrusion of anterior vertebral bodies, kyphotic angulation and very short long bones with dysplastic epiphyses and flarred, irregular, cupped metaphyses.
Xanthinuria type I (ORPHA:93601)
Type I xanthinuria, a type of classical xanthinuria (see this term), is a rare autosomal recessive disorder of purine metabolism (see this term) characterized by the isolated deficiency of xanthine dehydrogenase, causing hyperxanthinemia with low or absent uric acid and xanthinuria, leading to urolithiasis, hematuria, renal colic and urinary tract infections, while some patients are asymptomatic and others suffer from kidney failure. Less common manifestations include arthropathy, myopathy and duodenal ulcer.