TaoMedAI/RareMedData huggingface dataset:
Worster-Drought syndrome (ORPHA:3465)
Worster-Drought syndrome (WDS) is a form of cerebral palsy characterized by congenital pseudobulbar (suprabulbar) paresis manifesting as selective weakness of the lips, tongue and soft palate, dysphagia, dysphonia, drooling and jaw jerking.
Epidemiology
Prevalence is estimated at around 1/25,000-30,000, with a male predominance (male to female sex ratio: 3:1).
Clinical description
Mean age at diagnosis is 6 years. The main clinical features are spasticity and limited movements around the mouth and throat from an early age, and brisk jaw jerks. In severe cases, the muscles of the pharynx and larynx are also involved. Epilepsy, learning difficulties and behavioral disturbances are common. Mild pyramidal tetraplegia, glue ear, recurrent respiratory infections and aspiration, and gastroesophageal reflux may be present in up to 40% of patients. WDS is associated with bilateral lesions of the corticobulbar tract. Cranial nerves VII, X, and XII are implicated.
Diagnostic methods
Diagnosis is made on the basis of patient history, clinical examination and magnetic resonance imaging studies.
Differential diagnosis
The main differential diagnosis is the bilateral perisylvian polymicrogyria (see this term) which manifests with severe epilepsy Clinical overlap of WDS with congenital bilateral perisylvian polymicrogyria and Foix-Chavany-Marie syndrome (see these terms) has been noted. Some authors propose that these three conditions represent a continuum.
Genetic counseling
Most cases are sporadic but several families with more than one affected member have been reported. Inheritance in these families appeared to follow an autosomal dominant pattern with variable expression and penetrance.
Management and treatment
Management is dependent on the degree of feeding difficulties and speech problems but should include multidisciplinary approach by a pediatrician, speech therapist and educational psychologist. Children with epilepsy are treated with antiepileptic drugs.
Prognosis
WDS has a non-progressive course. The overall prognosis is good when nutritional problems, epilepsy and respiratory complications are properly managed.

                            Last update: 
                            October 2009


                            - Expert reviewer(s): 
                            Pr Jaime CAMPOS-CASTELLÓ
Wound myiasis (ORPHA:165955)
A rare cutaneous myiasis characterized by infestation of open wounds by dipterous fly larvae. Mucous membranes and body cavity openings can also be affected. The condition may be accompanied by fever, pain, and secondary infections and can lead to massive tissue destruction and even death. Predisposing factors for larval infestation are poor hygiene, advanced or very young age, alcoholism, diabetes, and vascular occlusive disease, among others.
Wrinkly skin syndrome (ORPHA:2834)
Wrinkly skin syndrome (WSS) is characterized by wrinkling of the skin of the dorsum of the hands and feet, an increased number of palmar and plantar creases, wrinkled abdominal skin, multiple skeletal abnormalities (joint laxity and congenital hip dislocation), late closing of the anterior fontanel, microcephaly, pre- and postnatal growth retardation, developmental delay and facial dysmorphism (a broad nasal bridge, downslanting palpebral fissures and hypertelorism).
Epidemiology
Prevalence is unknown but only around 30 cases have been reported in the literature so far.
Clinical description
Although the clinical picture is milder, WSS also shows significant overlap with classic features of ARCL2 (also known as Debré-type cutis laxa), leading to the suggestion that WSS and ARCL2 are variable manifestations of the same disorder. The clinical spectrum in WSS also closely resembles that of geroderma osteodysplastica (GO) and to some extent that of De Barsy syndrome (DBS; see these terms).
Etiology
Although the etiology in some patients remains unknown, mutations in the ATP6V0A2 gene (12q24.31) have been identified both in patients with WSS and in those with autosomal recessive cutis laxa (ARCL) type 2 (see this term). Mutations in the PYCR1 gene (17q25.3) have recently been identified in patients with phenotypes (wrinkly skin, osteopenia and progeroid features) overlapping with ARCL2, GO and DBS.
Diagnostic methods
Histological findings are not pathognomonic for WSS (elastic fiber abnormalities may be mild or nonspecific) but may allow WSS to be distinguished from ARCL2 and ARCL1 (see this term).
Genetic counseling
WSS is transmitted in an autosomal recessive manner.
Management and treatment
Treatment is symptomatic.
Prognosis
Patients with WSS syndrome have a variable outcome. The prognosis depends on the underlying mutation and appears to be most benign in children with a mutation in the ATP6V0A2 gene.

                            Last update: 
                            July 2010


                            - Expert reviewer(s): 
                             M GUILLARD  - Pr D.J. [Dirk] LEFEBER  - Pr Eva MORAVA-KOZICZ  - Pr R.A. [Ron] WEVERS
WT limb-blood syndrome (ORPHA:3466)
A rare constitutional aplastic anemia disorder characterized by severe hypo/aplastic anemia or pancytopenia associated with skeletal anomalies (such as radial/ulnar defects and hand/digit abnormalities) and an increased risk of leukemia. There have been no further descriptions in the literature since 1995.
X small rings (ORPHA:96201)
X small rings is a rare chromosome X structural anomaly, with highly variable phenotype, principally characterized by developmental delay, intellectual disability, short stature, craniofacial dysmorphism (incl. microcephaly, facial asymmetry, hypertelorism, long palpebral fissures, epicanthus, low-set or malrotated ears, broad nose with a flat nasal bridge, anteverted nares, long philtrum, thin upper lip, high arched palate, micrognathia) and skeletal anomalies (e.g. cubitus valgus, talipes equinovarus). Patients may also present heart malformations (e.g. ventricular septal defects, mitral valve stenosis), sacral dimple, soft tissue syndactyly, pigmented nevi, and seizures.
X-linked adrenal hypoplasia congenita (ORPHA:95702)
A rare genetic adrenal disease characterized by primary adrenal insufficiency (AI) and/or hypogonadotropic hypogonadism (HH). Male patients typically present with AI with acute onset in infancy or insidious onset in childhood. Clinical features of AI include hyperpigmentation, vomiting, poor feeding, failure to thrive, seizures, vascular collapse, and sometimes sudden death. HH manifests later as delayed or arrested puberty. In rare cases, patients become symptomatic in early adulthood with delayed-onset AI, partial HH, and/or infertility. Histologically, the adrenal glands lack the permanent adult cortical zone. The remaining cells are larger than fetal adrenal cells (''cytomegalic'') and contain characteristic nuclear inclusions.
X-linked calvarial hyperostosis (ORPHA:391327)
A rare, genetic, primary bone dysplasia with increased bone density disorder characterized by benign, isolated, calvarial thickening, presenting with prominent frontoparietal bones, a high forehead with ridging of the metopic and sagittal sutures, lateral frontal prominences, and facial dysmorphism comprising a flat nasal root and short, upturned nose. Increased intracranial pressure and cranial nerve entrapment are not associated. There have been no further descriptions in the literature since 1986.
X-linked central congenital hypothyroidism with late-onset testicular enlargement (ORPHA:329235)
X-linked central congenital hypothyroidism with late-onset testicular enlargement is a rare, genetic, endocrine disease characterized by central hypothyroidism, testis enlargement in adolescence resulting in adult macroorchidism, delayed pubertal testosterone rise with a subsequent delayed pubertal growth spurt, small thyroid gland, and variable prolactin and growth hormone deficiency.
X-linked centronuclear myopathy (ORPHA:596)
A rare X-linked congenital myopathy characterized by numerous centrally placed nuclei on muscle biopsy and that presents at birth with marked weakness, hypotonia and respiratory failure.
Epidemiology
The birth prevalence of X-linked centronuclear myopathy (XLMTM) is estimated at 1/50,000 males.
Clinical description
The disease is characterized by a severe phenotype in males presenting at birth with marked weakness, hypotonia and respiratory failure. Signs of antenatal onset are frequent and comprise reduced fetal movements and polyhydramnios. Thinning of the ribs is observed on chest radiographs of the newborn. Birth asphyxia may be the presenting feature. A family history of either male neonatal deaths or miscarriages is common. Affected infants are often macrosomic, with a body length above the 90th centile and large head circumference. External ophthalmoplegia is commonly associated. Testes are frequently undescended. Pyloric stenosis and cavernous hemangiomas of the liver have been reported in some long-term survivors.
Etiology
XLMTM is caused by mutations in the myotubularin (MTM1); Xq27.3-q28) gene.
Diagnostic methods
Diagnosis is based on typical histopathological findings on muscle biopsy in combination with suggestive clinical features. Genetic testing confirms the diagnosis.
Differential diagnosis
The main differential diagnoses include congenital myotonic dystrophy and other conditions characterized by severe neonatal hypotonia.
Antenatal diagnosis
Prenatal diagnosis is possible where the mutation has been previously identified in a family member.
Genetic counseling
The pattern of inheritance is x-linked recessive. Where the female is a carrier, the risk to male offspring inheriting the disease is 50%; female offspring have a 50% risk of being carriers. The degree of disease penetrance depends on skewed X-inactivation; the majority of female disease carriers are asymptomatic but may show signs of only mild muscle weakness or urinary incontinence, indicating smooth muscle involvement. Genetic counseling should be offered to all patients and families.
Management and treatment
There is currently no curative treatment available. Management is supportive and based on a multidisciplinary approach.
Prognosis
In the majority of cases, the course is fatal within the first months of life. A proportion of affected males may survive into their teens or beyond. In these cases, the survival depends on a substantial degree of medical intervention and often constant ventilation.

                            Last update: 
                            March 2020


                            - Expert reviewer(s): 
                            Pr Enrico BERTINI  - Dr Adele D'AMICO  - Pr Fabiana FATTORI
X-linked cerebral adrenoleukodystrophy (ORPHA:139396)
A progressive peroxisomal disease, characterized by endocrine dysfunction (adrenal failure and sometimes testicular insufficiency), progressive myelopathy and peripheral neuropathy, and leukodystrophy. Age of onset is highly variable, but often in the first decade.
X-linked cerebral-cerebellar-coloboma syndrome (ORPHA:163961)
X-linked cerebral-cerebellar-coloboma syndrome is a rare, genetic syndrome with a cerebellar malformation as major feature characterized by cerebellar vermis hypo- or aplasia, ventriculomegaly, agenesis of corpus callosum and abnormalities of the brainstem and cerebral cortex in association with ocular coloboma. Clinically, patients show hydrocephalus at birth, neonatal hypotonia with abnormal breathing pattern, ocular abnormalities with impaired vision, severe psychomotor delay, and seizures.
X-linked Charcot-Marie-Tooth disease type 1 (ORPHA:101075)
A rare genetic peripheral sensorimotor neuropathy characterized by an X-linked dominant inheritance pattern and adolescence onset in males of progressive, distal, moderate to severe muscle weakness and atrophy in lower extremities and intrinsic hand muscles, pes cavus, bilateral foot drop, reduced or absent tendon reflexes, as well as mild to moderate sensory impairment in lower extremities. Females tend to have milder manifestations or may be asymptomatic. Sensorineural deafness and (often transient) central nervous system involvement have also been reported.
X-linked Charcot-Marie-Tooth disease type 2 (ORPHA:101076)
A rare genetic peripheral sensorimotor neuropathy characterized by an X-linked recessive inheritance pattern and the infantile-to childhood-onset of progressive, distal muscle weakness and atrophy (more prominent in the lower extremities than in the upper extremities), pes cavus, and absent tendon reflexes. Sensory impairment and intellectual disability has been reported in some individuals.
X-linked Charcot-Marie-Tooth disease type 3 (ORPHA:101077)
A rare genetic peripheral sensorimotor neuropathy characterized by an X-linked recessive inheritance pattern and the childhood onset of progressive, distal muscle weakness and atrophy (beginning in the lower extremities and then affecting the upper extremities), as well as distal, pansensory loss in the upper and lower extremities, pes cavus, and absent or reduced distal tendon reflexes. Pain and paresthesia are frequently the initial sensory symptoms.
X-linked Charcot-Marie-Tooth disease type 4 (ORPHA:101078)
A rare genetic, axonal, peripheral sensorimotor neuropathy, characterized by an X-linked recessive inheritance pattern and the neonatal- to early childhood-onset of severe, slowly progressive, distal muscle weakness and atrophy (in particular of the peroneal group), as well as sensory impairment (with the lower extremities being more affected than the upper extremities), pes cavus, areflexia and hammertoes. Sensorineural hearing loss and cognitive impairment may also be associated. Females are asymptomatic and do not display the phenotype.
X-linked Charcot-Marie-Tooth disease type 5 (ORPHA:99014)
A rare genetic peripheral sensorimotor neuropathy characterized by infancy-to childhood onset of progressive distal muscle weakness and atrophy (first appearing and more prominent in the lower extremities than the upper) which usually manifests with foot drop and gait disturbance, bilateral, profound, prelingual sensorineural hearing loss and progressive optic neuropathy.
X-linked Charcot-Marie-Tooth disease type 6 (ORPHA:352675)
A rare genetic peripheral sensorimotor neuropathy characterized by principally axonal, peripheral sensorimotor neuropathy with an X-linked dominant inheritance pattern and the childhood-adolescence-onset of slowly progressive, moderate to severe, distal muscle weakness and atrophy of the lower extremities, as well as distal, panmodal sensory abnormalities, bilateral foot deformities (pes cavus, clawed toes), absent ankle reflexes and gait abnormalities (steppage gait). Females are usually asymptomatic or only present mild manifestations (mild postural hand tremor, mild wasting of hand intrinsic muscles).
X-linked cleft palate and ankyloglossia (ORPHA:324601)
X-linked cleft palate and ankyloglossia is a rare, genetic developmental defect during embryogenesis syndrome characterized by the association of complete, partial or submucous cleft palate and ankyloglossia. Patients may also present abnormal uvula (e.g. absent, bifid, shortened or laterally deviated), short lingual frenulum and dental anomalies (e.g. buccal crossbite, absent and/or misshapen teeth). Digital abnormalities, such as mild clinodactyly and/or syndactyly, have also been reported.
X-linked colobomatous microphthalmia-microcephaly-intellectual disability-short stature syndrome (ORPHA:431140)
X-linked colobomatous microphthalmia-microcephaly-intellectual disability-short stature syndrome is a rare syndromic microphthalmia disorder characterized by microphthalmia with coloboma (which may involve the iris, cilary body, choroid, retina and/or optic nerve), microcephaly, short stature and intellectual disability. Other eye abnormalities such as pendular nystagmus, esotropia and ptosis may also be present. Additional associated abnormalities include kyphoscoliosis, anteverted pinnae with minimal convolutions, diastema of the incisors and congenital pes varus.
X-linked complicated corpus callosum dysgenesis (ORPHA:1497)
A congenital, X-linked, clinical subtype of L1 syndrome, characterized by variable spastic paraplegia, mild to moderate intellectual disability, and dysplasia, hypoplasia or aplasia of the corpus callosum. In this subtype hydrocephalus, adducted thumbs, or absent speech are not observed.
X-linked complicated spastic paraplegia type 1 (ORPHA:306617)
A congenital, X-linked, clinical subtype of L1 syndrome, characterized by spastic paraplegia, mild to moderate intellectual disability and normal brain morphology. This subtype represents the milder end of the L1 syndrome spectrum.
X-linked cone dysfunction syndrome with myopia (ORPHA:90001)
X-linked cone dysfunction syndrome with myopia is characterised by moderate to high myopia associated with astigmatism and deuteranopia. Less than 10 families have been described so far. Transmission is X-linked recessive and the locus has been mapped to Xq28.
X-linked congenital generalized hypertrichosis (ORPHA:79495)
X-linked congenital generalized hypertrichosis is an extremely rare type of hypertrichosis lanuginosa congenita, a congenital skin disease, which is characterized by hair overgrowth on the entire body in males, and mild and asymmetric hair overgrowth in females. It is associated with a mild facial dysmorphism (anterverted nostrils, moderate prognathism), and, in a kindred, it was also associated with dental anomalies and deafness.
X-linked corneal dermoid (ORPHA:1661)
X-linked corneal dermoid (X-CND) is an exceedingly rare, benign, congenital, corneal tumor characterized by bilateral opacification of the cornea with superficial grayish layers and irregular raised whitish plaques, as well as fine blood vessels covering the central cornea, and intact peripheral corneal borders. No other ocular or systemic abnormality is noted. The pattern of inheritance described in the affected family is consistent with X-linked transmission.
X-linked distal spinal muscular atrophy type 3 (ORPHA:139557)
X-linked distal spinal muscular atrophy type 3 is a rare distal hereditary motor neuropathy characterized by slowly progressive atrophy and weakness of distal muscles of hands and feet with normal deep tendon reflexes or absent ankle reflexes and minimal or no sensory loss, sometimes mild proximal weakness in the legs and feet and hand deformities in males.
X-linked dominant chondrodysplasia, Chassaing-Lacombe type (ORPHA:163966)
X-linked dominant chondrodysplasia Chassaing-Lacombe type is a rare genetic bone disorder characterized by chondrodysplasia, intrauterine growth retardation (IUGR), hydrocephaly and facial dysmorphism in the affected males.
Epidemiology
Prevalence is unknown. To date, 10 patients (4 males and 6 females) in a single family have been reported through 4 generations.
Clinical description
Three male fetuses were diagnosed prenatally on ultrasonography (skeletal abnormalities and hydrocephaly) leading to termination of the pregnancies. The fourth affected male died at 6 days of life. The disease is severe and probably lethal in males, in whom the clinical picture includes short hands, brachydactyly, hydrocephaly and facial dysmorphism, including frontal bossing, low-set ears, short flat nose and microphthalmia. Other signs may include cerebellar hypoplasia and hyperkeratotic skin. X-rays show severe platyspondyly due to delayed ossification of the vertebrae, thin ribs, moderate shortening of the long bones, hypoplastic iliac wings, poorly ossified pubis, brachydactyly of the fingers and/or toes with cupped metacarpals, metatarsals, and phalanges and hypoplastic square calcaneus. The clinical picture in females is less severe and comprises short stature (128-151 cm), rhizomelic shortening of the limbs, short hands, brachymesophalangia of the 3rd and 4th toes, and may be associated with body asymmetry and mild cognitive impairment.
Etiology
X-linked dominant chondrodysplasia Chassaing-Lacombe type is due to a mutation in the histone deacetylase 6 HDAC6 gene (Xp11.3-q13.1) that causes a nucleotide substitution in the 3' untranslated region (UTR) of the HDAC6 transcript. This mutation lies in the seed sequence of microRNA-433 (hsa-miR-433) and abolishes the post-transcriptional regulation of HDAC6 expression by hsa-miR-433, resulting in the overexpression of the HDAC6 protein.
Genetic counseling
Inheritance is X-linked dominant.

                            Last update: 
                            February 2011


                            - Expert reviewer(s): 
                            Pr Didier LACOMBE
X-linked dyserythropoietic anemia with abnormal platelets and neutropenia (ORPHA:363727)
X-linked dyserythropoietic anemia with abnormal platelets and neutropenia is a rare, genetic, constitutional dyserythropoietic anemia disorder characterized by moderate to severe anemia without thrombocytopenia, variable degrees of neutropenia, and bone marrow biopsy findings of trilineage dysplasia and hypocellularity of erythroid and granulocytic lineages. Peripheral blood findings include anisocytosis, macrocytosis, poikilocytosis, elliptocytes, and fragmented erythrocytes.
X-linked Ehlers-Danlos syndrome (ORPHA:75497)
A rare systemic disease characterized by a severe phenotype in all male patients, combining abnormality of connective tissue typical for Ehlers-Danlos syndrome (including joint hypermobility, scoliosis, soft and doughy skin, hyperextensible skin, abnormal scarring, facial peculiarities, and generalized hypotonia, among others) and eventually lethal congestive heart failure due to polyvalvular disease. Female carriers are affected to a variable degree.
X-linked endothelial corneal dystrophy (ORPHA:293621)
X-linked endothelial corneal dystrophy (XECD) is a rare subtype of posterior corneal dystrophy (see this term) characterized by congenital ground glass corneal clouding or a diffuse corneal haze, and blurred vision in male patients.
Epidemiology
Prevalence of this rare corneal dystrophy is unknown. Males are affected more severely than females.
Clinical description
Affected males are born with clouding ranging from a diffuse haze to a ground-glass, milky appearance, which commonly causes blurred vision, and possible nystagmus. Female patients are asymptomatic but have crater-like endothelial abnormalities. The condition is progressive in males and non-progressive in females. In advanced cases, a subepithelial band keratopathy associated with endothelial changes that resemble moon craters is observed.
Etiology
XECD has been mapped to the long arm of the X-chromosome (Xq25) but the causative gene has not been identified.
Diagnostic methods
Light microscopy reveals focal discontinuities and degenerative changes in the corneal endothelial cells which underlie the crater-like changes seen clinically. Descemet membrane is irregularly thickened with small pits and excavations. The corneal epithelium and Bowman zone may be irregularly thinned.
Genetic counseling
Transmission is X-linked recessive.
Management and treatment
A penetrating keratoplasty may be indicated in males if corneal opacification impairs vision significantly. Procedures for repairing the posterior surface of the cornea, such as a deep lamellar endothelial keratoplasty (DLEK), Descemet stripping endothelial keratoplasty (DSEK), or Descemet stripping automated endothelial keratoplasty (DSAEK) are technically difficult in young children.

                            Last update: 
                            May 2012


                            - Expert reviewer(s): 
                            Dr Gordon KLINTWORTH
X-linked epilepsy-learning disabilities-behavior disorders syndrome (ORPHA:85294)
X-linked epilepsy-learning disabilities-behavior disorders syndrome is characterized by epilepsy, learning difficulties, macrocephaly, and aggressive behaviour. It has been described in males from a four-generation kindred. It is transmitted as an X-linked recessive trait and is likely to be caused by mutations in the gene encoding synapsin I (Xp11.3-q12).