TaoMedAI/RareMedData huggingface dataset:
Knobloch syndrome (ORPHA:1571)
A rare systemic disorder characterized by vitreoretinal and macular degeneration, as well as occipital encephalocele.
Epidemiology
The exact prevalence of Knobloch syndrome (KS) is unknown but less than 100 cases have been reported in the literature so far.
Clinical description
KS is characterized by early-onset severe myopia (usually becoming apparent in the first year of life), vitreoretinal degeneration with retinal detachment, macular abnormalities, and midline encephalocele (mainly in the occipital region). Predisposition to hydrocephalus is frequent. Ocular abnormalities vary and may include congenital cataract, iris abnormalities, and lens subluxation. Numerous extraocular abnormalities have been described: a single umbilical artery, pyloric stenosis, a flat nasal bridge, midface hypoplasia, bilateral epicanthic folds, abnormal lymphatic vessels in the lung, patent ductus arteriosus, cardiac dextroversion, generalized hyperextensibility of the joints, unusual palmar creases, and unilateral duplication of the renal collecting system. Structural brain defects, epilepsy and cognitive abnormalities have also been frequently reported. However, the full phenotypic spectrum is yet to be defined.
Etiology
The syndrome is caused by inactivating mutations in the collagen XVIII/endostatin gene (COL18A1; 21q22.3) which is highly expressed throughout the human eye. As a mutational hot-spot the c.4063_4064delCT is the most common mutation detected in Knobloch syndrome to date. İn one reported family the locus remains unmapped.
Diagnostic methods
Diagnosis is based on ocular abnormalities and occipital encephalocele (detected by computed tomography and magnetic resonance imaging). Magnetic resonance imaging of the brain would also help to detect associated developmental brain abnormalities. Sequencing of (COL18A1) gene.
Differential diagnosis
The differential diagnosis should include the following syndromes with or without encephalocele: Stickler, Wagner, Marshall, Meckel, and Walker-Warburg syndromes.
Genetic counseling
Transmission is autosomal recessive. Genetic counseling should be offered to at-risk couples (both individuals are carriers of a disease-causing mutation) informing them that there is a 25% risk of having an affected child at each pregnancy.
Management and treatment
Management of the ocular manifestations requires referral to an ophthalmologist specialist in retinopathies. Treatment modalities include retinal reattachment surgery, prophylactic treatment of the vitreoretinal pathology and photodynamic therapy. Encephalocele should be treated by surgical methods, aiming to restore normal anatomy with repair of the defective dura, bone and skin.
Prognosis
The eye findings in KS are severe and progressive, and regularly lead to bilateral blindness at a young age.

                            Last update: 
                            April 2020


                            - Expert reviewer(s): 
                            Pr Ahmet CAGLAYAN
Knuckle pads-leukonychia-sensorineural deafness-palmoplantar hyperkeratosis syndrome (ORPHA:2698)
A rare, syndromic genetic deafness disease characterized by symmetric or asymmetric knuckle pads (typically located on the distal and interphalangeal joints), leukonychia, diffuse palmoplantar keratoderma, and congenital, mild to moderate sensorineural deafness.
Kommerell diverticulum (ORPHA:99077)
Kommerell diverticulum (KD) is a developmental anomaly of the aortic arch characterized by a diverticulum at the proximal descending aorta of left or right arch configuration that gives rise to an aberrant subclavian artery. KD is primarily asymptomatic but may become symptomatic secondary to dilatation of KD, atheroma and fibrotic changes in paratracheal or paraesophageal tissue, presenting with signs of tracheal compression (more common in children), esophageal compression (dysphagia lusoria; more common in patients with a right sided aortic arch), chest pain, or blood pressure difference in the upper limbs. KD may also predispose toward aortic dissection or rupture.
Kosaki overgrowth syndrome (ORPHA:477831)
A rare genetic multiple congenital anomalies/dysmorphic syndrome characterized by postnatal tall stature with long hands and feet, scoliosis, distinctive dysmorphic facial features (prominent forehead, proptosis, downslanting palpebral fissures, broad nasal bridge, thin upper lip, and pointed chin), hyperelastic, thin, and fragile skin, lipodystrophy, and variable intellectual disability and neurological deterioration. Additional reported manifestations include craniosynostosis, camptodactyly, progressive flexion contractures, joint dislocation, and cerebrovascular complications, among others. Brain MRI may show extensive periventricular white matter lesions and other anomalies.
Kostmann syndrome (ORPHA:99749)
Kostmann syndrome is a rare, severe, congenital neutropenia disorder characterized by a lack of mature neutrophils (absolute neutrophil counts less than 500 cells/mm3) associated with frequent, recurrent bacterial infections (e.g. otitis media, pneumonia, sinusitis, urinary tract infections, abscesses of skin and/or liver) and increased promyelocytes in the bone marrow. Periodontal disease, as well as neurological symptoms, such as cognitive impairment, severe neurodegeneration and epilepsy, have been reported in some patients.
Kousseff syndrome (ORPHA:2351)
A rare syndromic central nervous system malformation characterized by the association of conotruncal heart defects, myelomeningocele and craniofacial dysmorphism similar to that seen in monosomy 22q11.
KRT1-related diffuse nonepidermolytic keratoderma (ORPHA:530838)
A rare, genetic, isolated diffuse palmoplantar keratoderma characterized by diffuse, mild to thick, finely demarcated hyperkeratosis of palms and soles. Additional clinical findings include knuckle pad-like keratoses on fingers, hyperkeratosis of umbilicus and areolae, diffuse dry skin, hyperhidrosis, hangnails and frequent fungal infections. Histological examination of lesions reveals orthokeratotic hyperkeratosis, acanthosis, hypergranulosis, and mild lymphocyte infiltrations in the upper dermis with no evidence of epidermolysis.
Kufor-Rakeb syndrome (ORPHA:306674)
Kufor-Rakeb syndrome (KRS) is a rare genetic neurodegenerative disorder characterized by juvenile Parkinsonism, pyramidal degeneration (dystonia), supranuclear palsy, and cognitive impairment.
Kuru (ORPHA:454745)
A rare acquired human prion disease characterized by rapidly progressive, fatal neurodegeneration, caused by the consumption of prion-containing tissue in endocannibalistic funeral rituals in Papua New Guinea until the late 1950s. After a decades-long asymptomatic period and a non-specific prodromal phase with headaches and arthralgia, the most prominent neurological feature is ataxia, in addition to other symptoms involving the cerebellum, brain stem, mid-brain, hypothalamus, and cerebral cortex, and emotional changes including inappropriate euphoria and compulsive laughter, or depression and apprehension. The last reported patient died in 2005 with an incubation period extending over four decades.
Kuskokwim syndrome (ORPHA:1149)
A very rare congenital contracture disorder, reported exclusively in Yup'ik Eskimos of the Kuskokwim River delta region of Alaska, characterized by multiple contractures of large joints (predominantly the knees and ankles) that present at birth or during childhood but are lifelong; deformities of the spine, pelvis and feet; and sometimes proximally or distally displaced patellae and muscle atrophy in the limbs with contractures. Additional radiological features include mild vertebral wedging, elongation of the vertebral pedicle, and clubbing of the distal clavicle. An autosomal recessive pattern of inheritance has been suggested.
Kyasanur forest disease (ORPHA:319254)
A rare infectious disease caused by the kyasanura forest disease virus and clinically characterized by an initial fever, headache and myalgia that can progress to a hemorrhagic disease and that in some cases is followed by a second phase characterized by neurological manifestations.
Kyphomelic dysplasia (ORPHA:1801)
A rare primary bone dysplasia characterized, radiologically, by short, stubby long bones, severely angulated femurs and lesser bowing of other long bones (mild, moderate or no bowing), short and wide iliac wings with horizontal acetabular roofs, platyspondyly and a narrow thorax, clinically manifesting with severe, disproportionate short stature. Regression of femora angulation is observed with advancing age.
Kyphoscoliosis-lateral tongue atrophy-hereditary spastic paraplegia syndrome (ORPHA:496689)
A rare complex hereditary spastic paraplegia characterized by neonatal to infantile onset of progressive spasticity in the lower limbs, hyperreflexia, tip-toe walking, pes equinus, and delayed motor developmental milestones. Kyphoscoliosis becomes evident in older patients, and most patients show atrophy of the lateral aspects of the tongue. Additional signs may include intellectual disability, language impairment, and moderate upper limb involvement.
Kyphoscoliotic Ehlers-Danlos syndrome due to FKBP22 deficiency (ORPHA:300179)
A rare subtype of kyphoscoliotic Ehlers-Danlos syndrome characterized by congenital muscle hypotonia, congenital or early-onset kyphoscoliosis (progressive or non-progressive), and generalized joint hypermobility with dislocations/subluxations (in particular of the shoulders, hips, and knees). Additional common features are skin hyperextensibility, easy bruising of the skin, rupture/aneurysm of a medium-sized artery, osteopenia/osteoporosis, blue sclerae, umbilical or inguinal hernia, chest deformity, marfanoid habitus, talipes equinovarus, and refractive errors. Subtype-specific manifestations include congenital hearing impairment (sensorineural, conductive, or mixed), follicular hyperkeratosis, muscle atrophy, and bladder diverticula. Molecular testing is obligatory to confirm the diagnosis.
Kyphoscoliotic Ehlers-Danlos syndrome due to lysyl hydroxylase 1 deficiency (ORPHA:1900)
A rare subtype of kyphoscoliotic Ehlers-Danlos syndrome characterized by congenital muscle hypotonia, congenital or early-onset kyphoscoliosis (progressive or non-progressive), and generalized joint hypermobility with dislocations/subluxations (in particular of the shoulders, hips, and knees). Additional common features are skin hyperextensibility, easy bruising of the skin, rupture/aneurysm of a medium-sized artery, osteopenia/osteoporosis, blue sclerae, umbilical or inguinal hernia, chest deformity, marfanoid habitus, talipes equinovarus, and refractive errors. Subtype-specific manifestations include skin fragility, atrophic scarring, scleral/ocular fragility/rupture, microcornea, and facial dysmorphology (like low‐set ears, epicanthal folds, down‐slanting palpebral fissures, high palate). Molecular testing is obligatory to confirm the diagnosis.
Kyphoscoliotic Ehlers-Danlos syndrome (ORPHA:536545)
A rare systemic disease for which two subtypes exist, either related to the gene PLOD1 or FKBP22, and for which the clinically overlapping characteristics include congenital muscle hypotonia, congenital or early-onset kyphoscoliosis (progressive or non-progressive), and generalized joint hypermobility with dislocations/subluxations (in particular of the shoulders, hips, and knees). Additional features which may occur in both subtypes are skin hyperextensibility, easy bruising of the skin, rupture/aneurysm of a medium-sized artery, osteopenia/osteoporosis, blue sclerae, umbilical or inguinal hernia, chest deformity, marfanoid habitus, talipes equinovarus, and refractive errors. Gene-specific features, with variable presentation, are additionally observed in each subtype.
Kyphosis-lateral tongue atrophy-myofibrillar myopathy syndrome (ORPHA:496686)
A rare genetic skeletal muscle disease characterized by neonatal to childhood onset of slowly progressive muscle weakness and atrophy primarily affecting the lower limbs, joint contractures, kyphosis or lordosis of the spine, lateral tongue atrophy, and pes equinus. Progression to upper limb involvement, facial weakness, language impairment, intellectual disability, and behavioral abnormalities have been reported in addition. Muscle biopsy shows myopathic changes with increased fiber size variation, internalized nuclei, fiber atrophy, as well as rod structures and core targetoid defects.
L-2-hydroxyglutaric aciduria (ORPHA:79314)
L-2-hydroxyglutaric aciduria is a primarily neurological form of 2-hydroxyglutaric aciduria (see this term) characterized by psychomotor retardation, cerebellar ataxia and variable macrocephaly or epilepsy.
Epidemiology
Exact prevalence and incidence of this disorder are not known but about 140 cases have been reported to date. The disorder appears to be pan-ethnic with cases reported worldwide.
Clinical description
Onset is often insidious in the first year of life. Presenting symptoms include motor retardation and epilepsy. The disease course is progressive leading to mental deterioration such as speech difficulties and motor deficits such as loss of independent walking. Most reported patients had macrocephaly. Other signs include hypotonia in the early stages and spasticity later in the course of the disease, extrapyramidal symptoms and behavioral disorders. An increased incidence of brain tumors has also been reported.
Etiology
L-2-hydroxyglutaric aciduria is thought to be caused by mutations in the L2HGDH gene (14q22.1) L-encoding mitochondrial 2-hydroxyglutarate dehydrogenase. More than 70 different mutations have been identified to date. However, several affected families did not have identifiable mutations in this gene.
Diagnostic methods
Urinary organic acid screening reveals a massive increase of 2HG, and subsequent chiral differentiation is needed establish the biochemical diagnosis of L-2-hydroxyglutaric aciduria. Diagnosis may be delayed due to the slowly progressive course of the disorder and is based on magnetic resonance imaging (MRI) or computed tomography (CT) findings, biochemical testing, and mutational analysis of the L2HGDH gene. MRI and CT findings are typically subcortical and paraventricular hyperintensities. Varying degrees of subcortical leukoencephalopathy and cerebellar atrophy have been observed.
Differential diagnosis
Urinary organic acid screening does not allow differentiation between L-2-hydroxygluratic acid and D-2-hydroxyglurac acid. Therefore, this differentiation has to be performed subsequently by a specialized laboratory.
Antenatal diagnosis
Prenatal diagnosis can be performed by mutational analysis and by the measurement of L-2-hydroxyglutaric acid in amniotic fluid.
Genetic counseling
L-2-hydroxyglutaric aciduria follows an autosomal recessive pattern of inheritance.
Management and treatment
There is currently no specific treatment for L-2-hydroxyglutaric aciduria. Supportive and symptomatic measures are therefore recommended.
Prognosis
Prognosis is poor but most patients reach adulthood.

                            Last update: 
                            May 2012


                            - Expert reviewer(s): 
                            Pr G.S. [Gajja] SALOMONS  - Dr E.A. [Eduard] STRUYS
L-Arginine:glycine amidinotransferase deficiency (ORPHA:35704)
L-Arginine:glycine amidinotransferase (AGAT) deficiency is a very rare type of creatine deficiency sydrome characterized by global developmental delay, intellectual disability, and myopathy.
Epidemiology
Less than 20 patients have been described with AGAT deficiency to date.
Clinical description
AGAT deficiency is characterized by global developmental delay, appearing in infancy, which can be associated with language impairment and autistic behavior in some, as well as a mild to moderate intellectual disability. Progressive muscle weakness and fatigability have been reported in older patients. Seizures and failure to thrive have also been described. If creatine supplementation is administered early enough, psychomotor delay may be avoided.
Etiology
AGAT deficiency is caused by mutations in the L-arginine:glycine amidinotransferase gene (GATM) located to chromosome 15q15.1. This gene encodes AGAT, which converts arginine and glycine to ornithine and guanidinoacetate in the creatine cycle pathway.
Genetic counseling
AGAT deficiency is transmitted in an autosomal recessive manner and genetic counseling is possible.

                            Last update: 
                            December 2014


                            - Expert reviewer(s): 
                            Dr Sylvia STOCKLER
L-ferritin deficiency (ORPHA:440731)
A rare genetic hematologic disease characterized by decreased or undetectable serum L-ferritin with otherwise normal laboratory parameters. Clinical signs and symptoms include generalized seizures, atypical restless leg syndrome, mild neuropsychologic impairment, and progressive hair loss. Asymptomatic cases have also been reported.
La Crosse encephalitis (ORPHA:83483)
An acute arboviral infection caused by the La Crosse bunyavirus transmitted by an infected mosquito, usually observed in infants, children or adolescents (6 months to 16 years), and characterized by the onset of flulike symptoms such as fever, chills, nausea, vomiting, headache, and abdominal pain, followed by the onset of encephalitis characterized by somnolence, obtundation, and even seizures, focal neurologic signs (asymmetrical reflexes or Babinski signs), paralysis or even coma. CE can leave sequelae such as residual epilepsy and neurocognitive deficits.
Lacrimoauriculodentodigital syndrome (ORPHA:2363)
A rare, genetic, multiple congenital anomalies/dysmorphic syndrome characterized by hypoplasia, aplasia or atresia of the lacrimal system, anomalies of the ears with sensorineural or mixed hearing loss, hypoplasia, aplasia or atresia of the salivary glands, dental anomalies, and digital malformations. Patients present obstruction of the nasal lacrimal ducts that can lead to epiphora, and chronic conjunctivitis due to alacrimia. Aplasia or hypoplasia of the salivary glands lead to dry mouth and early onset of severe dental caries. Dental features include late tooth eruption, small and peg-shaped lateral maxillary incisors and mild enamel dysplasia. The digital features are variable and include fifth finger clinodactyly, duplication of the distal phalanx of the thumb, triphalangeal thumb, and/or syndactyly. Unilateral radial aplasia and radial-ulnar synostosis have also been reported in association.
Lafora disease (ORPHA:501)
A rare, inherited, severe, progressive myoclonic epilepsy characterized by myoclonus and/or generalized seizures, visual hallucinations (partial occipital seizures), and progressive neurological decline.
Epidemiology
The prevalence varies: LD is seen worldwide but is more common in geographic isolates and areas with a high degree of inbreeding. In Western countries, prevalence is estimated to be below 1/1,000,000.
Clinical description
Onset occurs during adolescence, with generalised tonic-clonic or clonic-tonic-clonic seizures, action and resting myoclonus, negative myoclonus, and focal occipital seizures with transient amaurosis. The course is marked by prominent and rapid cognitive deterioration (the primary symptoms of which may precede the motor anomalies), and by the progressive increase in intensity of the seizures and myoclonus.
Etiology
LD is genetically heterogeneous. Mutations/deletions of the EPM2A gene, localised in 1995 to 6q24 (product: laforin), are found in 80% of cases. The less common EPM2B variant is localised on 6p22 (product: malin). However, these two localisations do not account for all cases of LD.
Diagnostic methods
The diagnosis of LD may be suspected on the basis of the family history, age at onset, typical appearance of symptoms, rapid worsening of cognitive function and detection of fairly typical electroencephalogram (EEG) features. It can easily be confirmed by axillary skin biopsy with detection of Lafora bodies (polyglucosan aggregates) in the sweat duct cells. Other biopsies, such as brain biopsy, are generally not necessary. Molecular biology is useful for diagnosis but the genetic heterogeneity does not allow LD to be excluded when none of the known mutations are detected.
Genetic counseling
Transmission is autosomal recessive. Genetic counselling and prenatal diagnosis are theoretically possible when the genetic anomaly has been documented in an affected member of the family.
Management and treatment
The treatment of LD with antiepileptic and antimyoclonic drugs remains purely symptomatic. Drugs that may aggravate myoclonus must be avoided. Psychological and social management is of utmost importance in LD.
Prognosis
Death occurs 4 to 10 years after onset in typical forms.

                            Last update: 
                            February 2007


                            - Expert reviewer(s): 
                            Dr Pierre GENTON
LAMA5-related multisystemic syndrome (ORPHA:521450)
A rare genetic systemic or rheumatologic disease characterized by infantile onset of skin anomalies (such as delayed wound healing with atrophic scars and mild alopecia with dry and brittle hair), retinal rod degeneration with night blindness, degenerative myopathy with muscle weakness, myalgia, and cramps, osteoarthritis, joint laxity, prolapse of internal organs, floating kidney syndrome, malabsorption syndrome, and hypothyroidism. The phenotype has been reported to be more severe in women than in men.
Lambert syndrome (ORPHA:1296)
A very rare syndrome described in four sibs of one French family and characterized by branchial dysplasia (malar hypoplasia, macrostomia, preauricular tags and meatal atresia), club feet, inguinal herniae and cholestasis due to paucity of interlobular bile ducts and intellectual deficit.