TaoMedAI/RareMedData huggingface dataset:
X-linked erythropoietic protoporphyria (ORPHA:443197)
A rare disorder of heme metabolism characterized by severe cutaneous photosensitivity in affected boys and sometimes in girls, manifesting in childhood.
Epidemiology
X-linked erythropoietic protoporphyria (XLPP) has been reported with a prevalence <1/1,000,000.
Clinical description
The disease manifests in infancy or childhood through the onset of severe acute cutaneous photosensitivity in affected boys, with tingling, burning and itching within few minutes of exposure to sunlight or illumination in the visible spectrum (in particular, in the Soret band [400 - 410 nm]), often accompanied by skin edema and redness. Pain may persist for several hours or days after the initial reaction. As protoporphyrin is a lipophilic molecule excreted by the liver, some XLPP patients may develop biliary lithiasis and liver damage. In heterozygous girls, the phenotypes vary from asymptomatic to severe.
Etiology
XLPP is due to gain-of-function mutations in the ALAS2 gene (NM_000032.4) encoding erythrocyte-specific aminolevulinic acid synthase 2.
Diagnostic methods
Diagnosis is based on the presence of high concentrations of protoporphyrin in plasma and red blood cells, and the detection of a plasma fluorescence peak at 635 nm. The percentage of zinc-bound protoporphyrin is reduced but remains higher than in autosomal EPP, and FECH enzyme activity is normal. A liver damage analysis is recommended. Genetic analysis (mutations in the ALAS2 gene) and family screening are also recommended.
Differential diagnosis
Differential diagnosis includes autosomal erythropoietic protoporphyria, phototoxic drug reactions, solar urticaria, contact dermatitis, angioedema, and hydroa vacciniforme.
Antenatal diagnosis
Antenatal diagnosis is theoretically possible, but not offered.
Genetic counseling
The transmission pattern is X-linked dominant.
Management and treatment
Treatment is based on preventive measures similar to those proposed for the treatment of autosomal erythropoietic protoporphyria. Since liver disease is the major risk in XLPP, regular monitoring of liver function is recommended. Sequential liver and bone marrow transplant should be considered in the treatment of severe cases with liver damage.
Prognosis
The prognosis of XLPP depends on the progression of liver disease. However, photosensitivity can affect patients' quality of life. In contrast to EPP, oral iron supplementation in XLPP patients with iron deficiency anemia reduces the concentration of protoporphyrins in the blood and improves symptoms.

                            Last update: 
                            March 2024


                            - Expert reviewer(s): 
                            Dr Neila TALBI | MetabERN*


                                * European Reference Network
X-linked external auditory canal atresia-dilated internal auditory canal-facial dysmorphism syndrome (ORPHA:500188)
A rare syndromic genetic deafness characterized by congenital hearing loss, atresia or stenosis of the external auditory canal, dilated internal auditory canal, malformation of the inner ear (incomplete separation of the cochlea basal turn from the fundus of the internal auditory canal), in combination with abnormal auricular shape and facial dysmorphism (including thick eyebrows, ptosis, broad nasal root, and telecanthus). Intelligence is normal and developmental delay is absent.
X-linked female restricted facial dysmorphism-short stature-choanal atresia-intellectual disability (ORPHA:480880)
A rare genetic multiple congenital anomalies/dysmorphic syndrome characterized by global developmental delay, intellectual disability, and dysmorphic facial features (such as facial asymmetry, prominent forehead, short palpebral fissures, low nasal bridge, smooth and long philtrum, thin upper lip, and low-set, posteriorly rotated, dysplastic ears), exclusively affecting females. Additional reported manifestations include short stature, choanal atresia, scoliosis, congenital ocular, dental, cardiac, and urogenital anomalies, as well as hypotonia, seizures, and structural brain abnormalities, among others.
X-linked hereditary sensory and autonomic neuropathy with deafness (ORPHA:139583)
A rare peripheral neuropathy characterized by the association of an axonal sensory and autonomic neuropathy with hearing loss.
Epidemiology
It has been described in a large five-generation Chinese family.
Clinical description
Onset occurred in the second decade of life (with an average age of onset of 13 years) with mild to severe hearing impairment due degeneration of the auditory nerve (type 1 auditory neuropathy), followed by late-onset of a diffuse and progressive peripheral sensory neuropathy.
Etiology
The causative gene was mapped to the AUNX1 locus on chromosome Xq23-27.3.
Genetic counseling
Transmission was X-linked recessive.

                            Last update: 
                            January 2009
X-linked immunoneurologic disorder (ORPHA:2571)
X-linked immunoneurologic disorder is characterized by immune deficiency and neurological disorders in females, and by neonatal death in males.
Epidemiology
The syndrome has been described in only one family with nine affected individuals (five males and four females) spanning two generations.
Clinical description
Symptomatic females present slowly progressive proximal muscle weakness, leg hyperreflexia, pes cavus, increased muscle tone in the legs, poor bladder function, static reduced night vision, and frequent sinopulmonary infections associated with IgG2 deficiency. Males present with low birth weight and severe hypotonia that leads to death in the neonatal period.
Etiology
The gene locus has been mapped to Xq26-qter.
Differential diagnosis
The syndrome should be considered in the differential diagnosis of hereditary spastic paraplegia in females and of other causes of severe neonatal hypotonia in males.
Genetic counseling
The condition is thought to be transmitted in an X-linked dominant manner.

                            Last update: 
                            August 2009
X-linked intellectual disability due to GRIA3 mutations (ORPHA:364028)
A rare, genetic, X-linked syndromic intellectual disability disorder characterized by moderate to severe intellectual disability associated with epilepsy, short stature, autistic features and behavioral problems, such as self injury and aggressive outbursts. Observed facial dysmorphism includes brachycephaly, prominent supraorbital ridges, and deep set eyes. Additional variable manifestations include malposition of feet, asthenic habitus, hyporeflexia, bowel occlusions, hydronephrosis, ren arcuatus, delayed motor development and disturbed sleep-wake cycle.
X-linked intellectual disability, Abidi type (ORPHA:85273)
X-linked intellectual disability, Abidi type is characterized by X-linked intellectual deficit and mild variable manifestations, including short stature, small head circumference, sloping forehead, hearing loss, abnormally shaped ears, and small testes. It has been described in eight affected males from three generations.
X-linked intellectual disability, Armfield type (ORPHA:85276)
X-linked intellectual disability, Armfield type is characterised by intellectual deficiency, short stature, seizures, and small hands and feet. It has been described in six males from three generations of one family. Three of them also had cataracts/glaucoma and two of them had cleft palate. The locus has been mapped to the terminal 8 Mb of Xq28.
X-linked intellectual disability, Cantagrel type (ORPHA:85277)
A rare X-linked intellectual disability characterized by marked neonatal hypotonia, progressive quadriparesia, severely delayed developmental milestones (walking at 3 years of age), gastroesophageal reflux, stereotypic movements of the hands, esotropia and infantile autism.
X-linked intellectual disability, Cilliers type (ORPHA:163971)
A rare developmental defect characterized by mild intellectual deficit associated with short stature, hypergonadotropic hypogonadism, microcephaly and mild facial dysmorphism (deep-set eyes, prominent supraorbital ridges, a high nasal bridge and large ears).
Epidemiology
It has been described in four males from one family.
Etiology
The syndrome is mapped to the Xq25-q26 region of the X-chromosome.
Genetic counseling
The syndrome was transmitted in an X-linked recessive manner.

                            Last update: 
                            May 2009
X-linked intellectual disability, Golabi-Ito-Hall type (ORPHA:93947)
An X-linked intellectual disability syndrome (XLMR) characterized by intellectual deficiency, microcephaly and short stature. It belongs to the group of disorders collectively referred to as Renpenning syndrome.
Epidemiology
It has been reported in only one family, with three affected patients.
Clinical description
Moderate to severe intellectual deficiency (IQ<50) is seen in all cases as are marked facial characteristics (long narrow face with upslanting palpebral fissures). Spastic diplegia is common. Golabi-Ito-Hall syndrome shows atrial septal defects and severe growth restriction (head circumference and length) but unlike other syndromes in the Renpenning group, small testes are not observed.
Etiology
It is caused by a missense mutation in the PQBP1 gene on exon 3 that leads to deregulated splicing that alters an amino acid in the gene's WW domain.
Genetic counseling
Golabi-Ito-Hall syndrome follows an X-linked recessive pattern of inheritance. Genetic testing is possible to identify carrier females and to inform them of the risk of passing on the gene to their offspring.

                            Last update: 
                            June 2012


                            - Expert reviewer(s): 
                            Pr Vincent DES PORTES
X-linked intellectual disability, Hedera type (ORPHA:93952)
X-linked intellectual disability, Hedera type is a rare X-linked intellectual disability syndrome characterized by an onset in infancy of delayed motor and speech milestones, generalized tonic-clonic seizures and drop attacks, and mild to moderate intellectual disability. Additional, less common manifestations include scoliosis, ataxia (resulting in progressive gait disturbance), and bilateral pes planovalgus. Physical appearance is normal with no dysmorphic features reported.
X-linked intellectual disability, Miles-Carpenter type (ORPHA:85283)
X-linked mental retardation, Miles-Carpenter type is characterised by severe intellectual deficit, microcephaly, exotropia and low digital arches.
Epidemiology
It has been described in four male members of one family.
Clinical description
Joint hypermobility, distal muscle wasting, hypogonadism and rocker bottom feet were also reported. Low digital arches and exotropia were described in several female members of the family.
Genetic counseling
Transmission is X-linked and the causative gene has been mapped to Xq13-q22.

                            Last update: 
                            March 2008
X-linked intellectual disability, Najm type (ORPHA:163937)
Najm type X-linked intellectual deficit is a rare cerebellar dysgenesis syndrome characterized by variable clinical manifestations ranging from mild intellectual deficit with or without congenital nystagmus, to severe cognitive impairment associated with cerebellar and pontine hypoplasia/atrophy and abnormalities of cortical development.
Epidemiology
Prevalence of this rare neurological syndrome is unknown. Up to 35 families have been reported to date.
Clinical description
Patients (mostly females) have been reported to have variable clinical manifestations including intellectual deficit, severe developmental delay, seizures, unsteady gait, sensorineural hearing loss and postnatal microcephaly (in most cases). Minor facial anomalies include: low or broad forehead, hypertelorism, long philtrum and micrognathia. Ocular findings are also variable and include congenital nystagmus, strabismus, cataracts, myopia or reduced visual acuity. Males appear to be more severely affected.
Etiology
Point mutations and deletions in the CASK gene (Xp11.4) have been found in patients with this syndrome.
Diagnostic methods
Magnetic resonance imaging (MRI) generally shows pontocerebellar hypoplasia/atrophy and simplified cortical gyri. Molecular genetic testing is needed to confirm diagnosis.
Genetic counseling
Transmission follows an X-linked dominant pattern.

                            Last update: 
                            February 2013


                            - Expert reviewer(s): 
                            Dr Ginevra ZANNI
X-linked intellectual disability, Nascimento type (ORPHA:163956)
X-linked intellectual disability, Nascimento type is a rare X-linked intellectual disability syndrome characterized by intellectual disability (with severe speech impairment), a myxedematous appearance, dysmorphic facial features (including large head, synophrys, prominent supraorbital ridges, almond-shaped and deep-set eyes, large ears, wide mouth with everted lower lip and downturned lip corners), low posterior hairline, short, broad neck, marked general hirsutism and abnormal hair whorls, skin changes (e.g. dry skin or hypopigmented spots), widely spaced nipples, obesity, micropenis, onychodystrophy and seizures.
X-linked intellectual disability, Pai type (ORPHA:85322)
A rare X-linked syndromic intellectual disability characterized by global developmental delay and severe intellectual disability, seizures, and recurrent lower respiratory tract infections, resulting in premature death in affected males. Additional reported manifestations include mild dysmorphic facial features (such as epicanthic folds, high nasal bridge, or small mouth), gait disturbances, brisk tendon reflexes, delayed bone age, and tapering fingers. No evident heterozygous manifestation has been reported in females.
X-linked intellectual disability, Schimke type (ORPHA:85285)
A rare X-linked syndromic intellectual disability characterized by intellectual deficit, growth retardation with short stature, deafness and ophthalmoplegia. Choreoathetosis with muscle spasticity generally appears during childhood.
X-linked intellectual disability, Seemanova type (ORPHA:85323)
X-linked intellectual disability, Seemanova type is characterised by microcephaly, intellectual deficit, growth retardation and hypogenitalism. It has been described in four boys from one family. A characteristic facies and ophthalmologic anomalies were also present and included microphthalmia, microcornea and cataract. Transmission is X-linked.
X-linked intellectual disability, Shashi type (ORPHA:85286)
X-linked intellectual disability, Shashi type is characterised by moderate intellectual deficit, obesity, macroorchidism and a characteristic facies (large ears, a prominent lower lip and puffy eyelids). It has been described in nine boys from two families. Transmission is X-linked and the causative gene has been localised to the q21.3-q27 region of the X chromosome.
X-linked intellectual disability, Shrimpton type (ORPHA:85324)
An X-linked syndromic intellectual disability characterised by severe intellectual disability, microcephaly and short stature in male patients. Strabismus and spastic diplegia have also been described.
X-linked intellectual disability, Siderius type (ORPHA:85287)
X-linked intellectual disability, Siderius type is characterised by mild to borderline intellectual deficit associated with cleft lip/palate. Preaxial polydactyly, large hands and cryptorchidism are sometimes present. The syndrome has been described in seven boys from two families. Transmission is X-linked and the syndrome is caused by mutations in the PHF8 gene, localised to the p11.21 region of the X chromosome.
X-linked intellectual disability, Snyder type (ORPHA:3063)
X-linked intellectual disability, Snyder type is a rare X-linked intellectual disability syndrome characterized by hypotonia, asthenic build with diminished muscle mass, severe generalized psychomotor delay, unsteady gait and moderate to severe intellectual disability, as well as a long, thin, asymmetrical face with prominent lower lip, long fingers and toes and nasal, dysarthric or absent speech. Bone abnormalities (e.g., osteoporosis, kyphoscoliosis, fractures, joint contractures) are also characteristic. Myoclonic, or myoclonic-like, seizures and renal abnormalities have been associated in some patients.
X-linked intellectual disability, Stevenson type (ORPHA:85325)
X-linked intellectual disability, Stevenson type is characterised by intellectual deficit, hypotonia, absent deep tendon reflexes, tapered fingers and excessive fingerprint arches, genu valgum, a characteristic face and small teeth. It has been described in four males from two generations of one family. The causative gene appears to be located in the q13 region of the X chromosome.
X-linked intellectual disability, Stocco Dos Santos type (ORPHA:85288)
X-linked intellectual disability, Stocco Dos Santos type is characterised by severe intellectual deficit with hyperactivity, language delay, congenital hip luxation, short stature, kyphosis and recurrent respiratory infections. Aggressive behaviour and frequent epileptic seizures may also be present. The syndrome has been described in four boys from the same family. Transmission is X-linked and is caused by mutations in the KIAA1202 gene, localised to the Xp11.2 region.
X-linked intellectual disability, Stoll type (ORPHA:85326)
X-linked intellectual disability, Stoll type is characterised by intellectual deficit, short stature and characteristic facies (hypertelorism, prominent forehead, frontal bossing, a broad nasal tip and anteverted nares). It has been described in four males from three generations of the same family. Two females from this family also displayed intellectual deficit and the characteristic facies. Transmission is X-linked.
X-linked intellectual disability, Van Esch type (ORPHA:163976)
A rare, genetic, syndromic intellectual disability characterized by developmental delay, mild to moderate intellectual disability, low birth weight, moderate to severe short stature, microcephaly and variable hypergonadotropic hypogonadism. Mild facial dismorfism include upslanted palpebral fissures and prominent nasal bridge.
X-linked intellectual disability, Wilson type (ORPHA:85290)
X-linked intellectual disability, Wilson type is characterised by severe intellectual deficit with mutism, epilepsy, growth retardation and recurrent infections. It has been described in three males from three generations of one family. The causative gene has been localised to the 11p region of the X chromosome.
X-linked intellectual disability-acromegaly-hyperactivity syndrome (ORPHA:85327)
X-linked intellectual disability-acromegaly-hyperactivity syndrome is characterised by severe intellectual deficit, acromegaly and hyperactivity. The syndrome has been described in two half-brothers. Dysarthria, aggressive behaviour, a characteristic facies (an acromegalic and triangular face with a long nose) and macroorchidism were also present. The mother displayed moderate intellectual deficit and milder facial anomalies. Central nervous system anomalies were identified in the two boys: subarachnoid cysts and hyperdensity in the pontine region.
X-linked intellectual disability-ataxia-apraxia syndrome (ORPHA:85338)
A rare, X-linked syndromic intellectual disability disorder characterized by non-progressive ataxia, apraxia, variable intellectual disability and/or visuospatial, visuographic and visuoconstructive dysfunctions in male patients. Seizures, congenital clubfoot and macroorchidism have also been associated. Partial clinical expression was noted in obligate female carriers. There have been no further descriptions in the literature since 1992.
X-linked intellectual disability-cardiomegaly-congestive heart failure syndrome (ORPHA:324410)
X-linked intellectual disability-cardiomegaly-congestive heart failure syndrome is a rare X-linked syndromic intellectual disability disorder characterized by profound intellectual disability, global developmental delay with absent speech, seizures, large joint contractures, abnormal position of thumbs and middle-age onset of cardiomegaly and atrioventricular valve abnormalities, resulting in subsequent congestive heart failure. Additional features include variable facial dysmorphism (notably large ears with overfolded helix) and large testes.
X-linked intellectual disability-cerebellar hypoplasia syndrome (ORPHA:137831)
X-linked intellectual deficit-cerebellar hypoplasia, also known as OPHN1 syndrome, is a rare syndromic form of cerebellar dysgenesis characterized by moderate to severe intellectual deficit and cerebellar abnormalities.
Epidemiology
OPHN1 syndrome is very rare. To date, up to 12 families have been reported.
Clinical description
Affected male patients present moderate to severe intellectual disability, hypotonia, severe developmental delay, early-onset complex partial or tonic-clonic seizures, strabismus, dysmetria and occasionally ataxia. Cryptorchidism and genital hypoplasia have been reported. Some patients have abnormal behavior and a characteristic facial phenotype (long face, prominent forehead, infraorbital creases, deep-set eyes, upturned philtrum and large ears). Carrier females have been reported to have mild learning disabilities, mild cognitive impairment, strabismus, and subtle facial changes.
Etiology
Various mutations including deletions and splice site mutations in the OPHN1 gene (Xq12) have been reported in patients with this syndrome.
Diagnostic methods
Neuroradiological findings include posterior vermis dysgenesis, vermian parasagittal cleft, cerebellar hypoplasia, cortical atrophy, and enlargement of the cerebral ventricles. Molecular genetic testing is needed to confirm diagnosis.
Genetic counseling
Transmission appears to follow an X-linked semi-dominant pattern.

                            Last update: 
                            February 2013


                            - Expert reviewer(s): 
                            Dr Ginevra ZANNI
X-linked intellectual disability-cerebellar hypoplasia-spondylo-epiphyseal dysplasia syndrome (ORPHA:459070)
A rare genetic multiple congenital anomalies/dysmorphic syndrome characterized by global developmental delay, intellectual disability, growth retardation, hypotonia, cerebellar symptoms such as ataxia, spondyloepiphyseal dysplasia, and dysmorphic craniofacial features (including microcephaly, dolichocephaly, prominent ears, epicanthus, broad nasal bridge, long and flat philtrum, or small mouth). Additional reported manifestations are epilepsy, retinitis pigmentosa, and urogenital abnormalities, among others. Brain imaging may show cerebellar hypoplasia.
X-linked intellectual disability-craniofacioskeletal syndrome (ORPHA:163979)
X-linked intellectual disability-craniofacioskeletal syndrome is a rare, hereditary, syndromic intellectual disability characterized by craniofacial and skeletal abnormalities in association with mild intellectual disability in females and early postnatal lethality in males. In addition to mild cognitive impairment, females present with microcephaly, short stature, skeletal features and extra temporal lobe gyrus. In males, intrauterine growth impairment, cardiac and urogenital anomalies have been reported.
X-linked intellectual disability-cubitus valgus-dysmorphism syndrome (ORPHA:85280)
X-linked intellectual disability-cubitus valgus-dysmorphism syndrome is characterised by moderate intellectual deficit, marked cubitus valgus, mild microcephaly, a short philtrum, deep-set eyes, downslanting palpebral fissures and multiple nevi. Less than ten individuals have been described so far. Transmission is thought to be X-linked recessive.
X-linked intellectual disability-Dandy-Walker malformation-basal ganglia disease-seizures syndrome (ORPHA:1568)
A rare central nervous system malformation characterized by severe intellectual deficit, early hypotonia with progression to spasticity and contractures, choreoathetosis, seizures, dysmorphic face (long face with prominent forehead), and brain imaging abnormalities such as Dandy-Walker malformation, and iron deposition.