TaoMedAI/RareMedData huggingface dataset:
Lethal congenital contracture syndrome type 1 (ORPHA:1486)
Lethal congenital contracture syndrome type 1 is a rare, genetic arthrogryposis syndrome characterized by total fetal akinesia (detectable since the 13th week of gestation) accompanied by hydrops, micrognathia, pulmonary hypoplasia, pterygia and multiple joint contractures (usually flexion contractures in the elbows and extension in the knees), leading invariably to death before the 32nd week of gestation. Lack of anterior horn motoneurons, severe atrophy of the ventral spinal cord and severe skeletal muscle hypoplasia are characteristic neuropathological findings, with no evidence of other organ structural anomalies.
Lethal congenital contracture syndrome type 2 (ORPHA:137776)
Lethal congenital contracture syndrome type 2 is a rare arthrogryposis syndrome characterized by multiple congenital contactures (typically extended elbows and flexed knees), micrognathia, anterior horn cell degeneration, skeletal muscle atrophy (mainly in the lower limbs), presence of a markedly distended urinary bladder and absence of hydrops, pterygia and bone fractures. Other craniofacial (e.g. cleft palate, facial palsy) and ocular (e.g. anisocoria, retinal detachment) anomalies may be additionally observed. The disease is usually neonatally lethal however, survival into adolescence has been reported.
Lethal congenital contracture syndrome type 3 (ORPHA:137783)
Lethal congenital contracture syndrome type 3 is a rare arthrogryposis syndrome characterized by clinical features identical to Lethal congenital contracture syndrome type 2 (i.e. multiple congenital contactures (typically extended elbows and flexed knees), micrognathia, anterior horn cells degeneration, skeletal muscle atrophy (mainly in the lower limbs), in the absence of hydrops, pterygia or bone fractures), but without bladder enlargement.
Lethal congenital contracture syndrome (ORPHA:294965)
A group of rare arthrogryposis syndromes characterized by fetal akinesia, multiple congenital contractures, anterior horn cell degeneration, skeletal muscle atrophy, and other features, depending on the subtype. All types are lethal in the fetal or neonatal period.
Lethal faciocardiomelic dysplasia (ORPHA:1972)
An extremely rare polymalformative syndrome.
Epidemiology
It was described only once, in 1975, in 3 affected males in a sibship of 13, from second-cousin parents.
Clinical description
Patients were all of low birth weight, had microretrognathia, microstomia, and microglossia, hypoplasia of the radius and ulna with radial deviation of the hands, simian creases and hypoplasia of fingers I and V, hypoplasia of the fibula and tibia with talipes and wide space between toes I and II, and severe malformation of the left heart which may have been responsible for death of all 3 in the first week or so of life.

                            Last update: 
                            December 2011
Lethal fetal brain malformation-duodenal atresia-bilateral renal hypoplasia syndrome (ORPHA:444069)
A rare genetic lethal multiple congenital anomalies/dysmorphic syndrome characterized by mid-gestation lethality and features of a ciliopathy. Clinical manifestations include hydrocephalus, cerebellar vermis hypoplasia, corpus callosum agenesis, duodenal atresia, gastrointestinal malrotation, bilateral renal hypoplasia, and dysmorphic craniofacial features (such as microcephaly, hypertelorism, low-set ears, prominent nose, short columella, cleft palate, micrognathia, and wide mouth).
Lethal fetal cerebrorenogenitourinary agenesis/hypoplasia syndrome (ORPHA:439897)
Lethal fetal cerebrorenogenitourinary agenesis/hypoplasia syndrome is a rare, genetic developmental defect during embryogenesis malformation syndrome characterized by intrauterine growth restriction, flexion arthrogryposis of all joints, severe microcephaly, renal cystic dysplasia/agenesis/hypoplasia and complex malformations of the brain (cerebral and cerebellar hypoplasia, vermis, corpus callosum and/or occipital lobe agenesis, with or without arhinencephaly), as well as of the genitourinary tract (ureteral agenesis/hypoplasia, uterine hypoplasia and/or vaginal atresia), leading to fetal demise.
Lethal hemolytic anemia-genital anomalies syndrome (ORPHA:1046)
A rare genetic disease characterized by lethal non-spherocytic, non-immune hemolytic anemia, in association with abnormalities of the external genitalia (such as micropenis and hypospadias). Reported dysmorphic features include flat occiput, dimpled earlobes, deep plantar creases, and increased space between the first and second toes. There have been no further descriptions in the literature since 1995.
Lethal hydranencephaly-diaphragmatic hernia syndrome (ORPHA:480528)
Lethal hydranencephaly-diaphragmatic hernia syndrome is a rare, genetic, lethal, multiple congenital anomalies syndrome characterized by hydranencephaly and diaphragmatic hernia, as well as macrocephaly, a widely open anterior fontanel, scaphoid abdomen and hypotonia. Additionally, congenital heart defects, polyhydramnios and pulmonary hypertension have also been associated.
Lethal infantile mitochondrial myopathy (ORPHA:254857)
Lethal infantile mitochondrial myopathy is a rare mitochondrial oxidative phosphorylation disorder characterized by progressive generalized hypotonia, progressive external ophthalmoplegia and severe lactic acidosis, which results in early fatality (days to months after birth). Patients may present with lethargy and areflexia and may associate additional features, such as cardiomyopathy, renal dysfunction, liver involvement and seizures.
Lethal intrauterine growth restriction-cortical malformation-congenital contractures syndrome (ORPHA:2570)
A rare and fatal central nervous system malformation occurring during embryogenesis, presenting prenatally with holoprosencephaly and fetal hypokinesia as major features. Other manifestations include microcephaly, multiple contractures and intrauterine growth restriction. There have been no further descriptions in the literature since 1988.
Lethal Kniest-like dysplasia (ORPHA:2347)
A rare, lethal, congenital, chondrodysplasia disorder characterized by dumbbell-shaped long bones with markedly shortened diaphyses and metaphyseal irregularities associated with a 'Swiss cheese' appearance of the cartilage matrix, as well as distinctive changes in the growth plate and resting cartilage, resulting in death in the neonatal period. There have been no further descriptions in the literature since 1983.
Lethal Larsen-like syndrome (ORPHA:2371)
A rare developmental defect with connective tissue involvement characterized by multiple joint dislocations, flattened facial appearance, abnormal palmar creases, laryngotracheomalacia, and pulmonary hypoplasia. Additional signs may include a bifid tongue, micrognathia, non-immune hydrops fetalis, and brain dysplasia. The disease is lethal shortly after birth due to respiratory insufficiency.
Lethal left ventricular non-compaction-seizures-hypotonia-cataract-developmental delay syndrome (ORPHA:478049)
Lethal left ventricular non-compaction-seizures-hypotonia-cataract-developmental delay syndrome is rare, genetic, neurometabolic disease characterized by global developmental delay, severe hypotonia, seizures, cataracts, cardiomyopathy (including left or bi-ventricular hypertrophy, dilated cardiomyopathy) and left ventricular non-compaction, typically resulting in infantile or early-childhood death. Patients usually present metabolic lactic acidosis, failure to thrive, head lag, respiratory problems and decrease in respiratory chain complex activity. Highly variable cerebral abnormalities have been reported and include microcephaly, prominent extra-axial cerebrospinal fluid spaces, diffuse neuronal loss and cortical/white matter gliosis.
Lethal neonatal spasticity-epileptic encephalopathy syndrome (ORPHA:435845)
A rare genetic neurological disorder characterized by neonatal onset of rigidity and intractable seizures, with episodic jerking already beginning in utero. Affected infants have small heads, remain visually inattentive, do not feed independently, and make no developmental progress. Frequent spontaneous apnea and bradycardia usually culminate in cardiopulmonary arrest and death in infancy, although some cases were described with a milder clinical course and survival into childhood.
Lethal occipital encephalocele-skeletal dysplasia syndrome (ORPHA:293925)
Lethal occipital encephalocele-skeletal dysplasia syndrome is a rare, genetic, bone development disorder characterized by occipital and parietal bone hypoplasia leading to occipital encephalocele, calvarial mineralization defects, craniosynostosis, radiohumeral fusions, oligodactyly and other skeletal anomalies (arachnodactyly, terminal phalangeal aplasia of the thumbs, bilateral absence of the great toes, pronounced bilateral angulation of femora, shortened limbs, advanced osseous maturation). Fetal death in utero is associated.
Lethal omphalocele-cleft palate syndrome (ORPHA:2736)
A rare multiple congenital anomalies/dysmorphic syndrome characterized by the association of omphalocele and cleft palate. Other reported features include cleft lip, bifid uvula, bilateral talipes equinovarus, bicornuate uterus, and hydrocephalus internus. The condition is lethal in infancy.
Lethal polymalformative syndrome, Boissel type (ORPHA:210144)
A rare, genetic, lethal, multiple congenital anomalies/dysmorphic syndrome characterized by failure to thrive, severe developmental delay, severe postanatal microcephaly, frequent congenital cardiac defects and characteristic facial dysmorphysm (including coarse face with anteverted nostrils, thin vermillion, prominent alveolar ridge and retro- or micrognatia). Additional common features include neurologic abnormalities (hyper-/hypotonia, sensorineural deafness, hydrocephalus, cerebral atrophy, seizures), as well as brachydactyly, cutis marmorata and genital anomalies.
Lethal recessive chondrodysplasia (ORPHA:1423)
Lethal recessive chondrodysplasia is an extremely rare lethal form of chondrodysplasia characterized by severe micromelic dwarfism, short and incurved limbs with normal hands and feet, facial dysmorphism (disproportionately large skull, frontal prominence, slightly flattened nasal bridge and short neck), muscular hypotonia, hyperlaxity of the extremities, and a narrow thorax. Most patients die of respiratory distress during the first hours or weeks of life. There have been no further descriptions in the literature since 1988.
Leukocyte adhesion deficiency type I (ORPHA:99842)
Leukocyte adhesion deficiency type I (LAD-I) is a form of LAD (see this term) characterized by life-threatening, recurrent bacterial infections.
Epidemiology
LAD-I affects 1 individual per million.
Clinical description
Usually the first signs occur in infancy or early childhood. Patients present recurrent, life-threatening bacterial infections of the skin, mouth, and respiratory tract. Delayed umbilical cord separation is common. Skin infections may evolve into large ulcers. Severe periodontitis is often present later in life and leads to early tooth loss. A lack of swelling, redness, heat, or pus is observed in the area of infection.
Etiology
LAD-I is caused by mutations in the ITGB2 gene (21q22.3), encoding the beta-2-integrin, CD18, which is essential for firm adhesion of leukocytes to the endothelium. Severity of the disease correlates with the degree of CD18 deficiency.
Diagnostic methods
Diagnosis is based on complete blood counts revealing neutrophilic leukocytosis. Flow cytometric analyses reveal reduced CD18 expression on leukocytes. Genetic analyses of mutations in the ITGB2 gene confirm the diagnosis.
Differential diagnosis
Differential diagnoses include IRAK-4 deficiency, autosomal dominant hyper IgE syndrome, chronic granulomatous disease, other primary immunodeficiencies (see these terms) and a leukemoid reaction.
Antenatal diagnosis
Antenatal diagnosis is possible through biochemical or molecular analysis of chorionic villus cells or amniocytes in affected families for which the mutation has been identified. Flow cytometry can be performed at 20 weeks of gestation.
Genetic counseling
Transmission is autosomal recessive.
Management and treatment
Management should focus on controlling infections and includes antibiotics. Hematopoietic cell transplantation represents the only cure for LAD-I, but gene therapy may be available in the future.
Prognosis
Prognosis depends on the severity of the disease. Without hematopoietic stem cell transplantation, death in patients with severe LAD-I occurs from infection within the first 2 years of life, whereas patients with a moderate form of the disease have abetter chance of surviving into adulthood. Survival rate after bone marrow transplantation is 75%.

                            Last update: 
                            May 2009


                            - Expert reviewer(s): 
                            Pr Amos ETZIONI
Leukocyte adhesion deficiency type II (ORPHA:99843)
Leukocyte adhesion deficiency type II (LAD-II) is a form of LAD (see this term) characterized by recurrent bacterial infections, severe growth delay and severe intellectual deficit.
Epidemiology
LAD-II is extremely rare: less than 10 cases have been reported so far.
Clinical description
The first signs usually occur in infancy or early childhood. Patients present recurrent bacterial infections, severe growth delay resulting in short stature, and severe intellectual deficit. Patients have the Bombay phenotype (they do not express the H antigen). Facial dysmorphism is common, characterized mainly by a depressed nasal bridge. Severe periodontitis is often present later in life and leads to early tooth loss. In adulthood, intellectual deficit and growth retardation, rather than infections, dominate the clinical picture.
Etiology
LAD-II is a carbohydrate-deficient glycoprotein syndrome (CDG syndrome; see this term) and is therefore also referred to as CDG IIc. It results from mutations in the SLC35C1 gene (11p11.2), encoding the guanosine 5'-diphosphate (GDP)-fucose transporter localized in the Golgi apparatus. This is a specific fucose transporter that translocates GDP-fucose from the cytosol to the Golgi where it is used as a substrate for fucosylation.
Diagnostic methods
Diagnosis is based on clinical findings and complete blood counts revealing leukocytosis with neutrophilia. Blood typing is essential to look for the Bombay blood group, which is present in all patients with LAD-II and is extremely rare in the general population. Final diagnosis is based on genetic analysis.
Differential diagnosis
There is no differential diagnosis as the clinical symptoms of recurrent infections, leukocytosis, the Bombay blood group, and severe growth and intellectual deficit are unique to LAD-II.
Antenatal diagnosis
Antenatal diagnosis through biochemical or molecular analysis of chorionic villus cells or amniocytes is possible in families for which the mutation has been identified.
Genetic counseling
Transmission is autosomal recessive.
Management and treatment
Management should focus on controlling infections and includes antibiotics. Fucose replacement may improve phagocytic function in some cases.
Prognosis
Infections in LAD-II are rarely life-threatening and thus patients may live to adulthood.

                            Last update: 
                            May 2009


                            - Expert reviewer(s): 
                            Pr Amos ETZIONI
Leukocyte adhesion deficiency type III (ORPHA:99844)
Leukocyte adhesion deficiency type III (LAD-III) is a form of LAD (see this term) characterized by both severe bacterial infections and a severe bleeding disorder.
Epidemiology
LAD-III is extremely rare: only 17 patients have been reported so far.
Clinical description
Usually the first signs occur in infancy or early childhood. Patients present LAD-I life-threatening infections and a Glanzmann thrombasthenia-like bleeding disorder (see these terms). A lack of pus is observed in infected areas.
Etiology
LAD-III is caused by mutations in the FERMT3 gene (11q13.1), which encodes kindlin-3 in hematopoietic cells. The FERMT3 mutations lead to an activation defect of all beta-integrins.
Diagnostic methods
Diagnosis is based on clinical findings and complete blood counts revealing leukocytosis with neutrophilia. Platelet aggregation assays and genetic analysis confirm the diagnosis.
Differential diagnosis
Differential diagnoses include LAD-I, Glanzmann thrombasthenia (see these terms), and leukemoid reaction. Antenatal diagnosis may be confirmed through biochemical or molecular analysis of chorionic villus cells.
Genetic counseling
Transmission is autosomal recessive.
Management and treatment
Management should focus on controlling infections and includes symptomatic treatment with antibiotics and blood transfusions. Bone marrow transplantation is the only available curative treatment option.
Prognosis
Prognosis is poor and death occurs in early infancy if bone marrow transplantation is not performed.

                            Last update: 
                            May 2009


                            - Expert reviewer(s): 
                            Pr Amos ETZIONI
Leukocyte adhesion deficiency (ORPHA:2968)
Leukocyte adhesion deficiency (LAD) is a primary immunodeficiency characterized by defects in the leukocyte adhesion process, marked leukocytosis and recurrent infections.
Epidemiology
Prevalence is unknown, but less than 350 cases have been reported so far.
Clinical description
Usually the first signs occur in infancy or early childhood. Three distinct defects in the leukocyte adhesion cascade have been defined leading to three distinct entities. LAD-I (see this term) is characterized by life-threatening, recurrent bacterial infections. LAD-II (see this term) presents with leukocytosis, recurrent infections, severe growth delay and intellectual deficit. LAD-III (see this term; also called LAD-I variant) is characterized by both severe bacterial infections and a severe bleeding disorder.
Etiology
LAD results from an impaired step in the inflammatory process, namely, the migration of leukocytes from the blood vessels to sites of infection, which requires adhesion of leukocytes to the endothelium. LAD-I is caused by mutations in the ITGB2 gene (21q22.3), encoding the beta-2-integrin CD18. LAD-II results from mutations in the SLC35C1 gene (11p11.2), encoding the guanosine 5'-diphosphate (GDP)-fucose transporter. LAD-III is caused by mutations in the FERMT3 gene (11q13.1), encoding kindlin-3 in hematopoietic cells.
Diagnostic methods
Diagnosis is based on the clinical symptoms and on a complete blood count revealing neutrophilia. In LAD-I and LAD-II, flow cytometry should be performed for CD18 and CD15 respectively. In LAD-III, platelet aggregation assays should be performed. In all cases, a genetic analysis confirms the diagnosis.
Differential diagnosis
Differential diagnoses include IRAK-4 deficiency, autosomal dominant hyper IgE syndrome, chronic granulomatous disease (see these terms), neutrophil dysfunction and a leukemoid reaction.
Antenatal diagnosis
Antenatal diagnosis is feasible by genetic analysis of chorionic villus samples.
Genetic counseling
In all cases, transmission is autosomal recessive. Genetic counseling should always be offered to the patients and their families.
Management and treatment
Management depends on the type of LAD. Treatment should focus on controlling infections and includes antibiotics and, in many cases, bone marrow transplantation. Without hematopoietic stem cell transplantation, patients with severe LAD-I and LAD-III usually die from infection within the first 2 years of life.
Prognosis
The survival rate in patients with LAD-I who undergo bone marrow transplantation is 75%. Some patients with LAD-II survive to adulthood.

                            Last update: 
                            May 2009


                            - Expert reviewer(s): 
                            Pr Amos ETZIONI
Leukoencephalopathy with bilateral anterior temporal lobe cysts (ORPHA:139444)
A rare, nonprogressive, neurological disorder marked by intellectual deficit, spasticity and motor retardation associated with characteristic MRI findings of anterior bilateral temporal lobe cysts and multilobar leukoencephalopathy. So far, around 30 cases have been reported in the literature. Onset occurs in the first few months of life. Sensorineural deafness and microcephaly have also been reported. The etiology is unknown but an autosomal recessive mode of inheritance has been suggested.
Leukoencephalopathy with brain stem and spinal cord involvement-high lactate syndrome (ORPHA:137898)
This disease is characterised by progressive cerebellar ataxia with pyramidal and spinal cord dysfunction, associated with distinctive MRI anomalies and increased lactate in the abnormal white matter.
Epidemiology
So far, 38 cases have been reported.
Clinical description
Onset occurs in early childhood. Epilepsy and cognitive decline have also been described.
Etiology
The syndrome is caused by mutations in the DARS2 gene, which encodes mitochondrial aspartyl-tRNA synthetase.
Diagnostic methods
MRI reveals inhomogeneous periventricular and deep white matter anomalies, with involvement of the cerebellar connections, the entire length of the pyramidal and sensory tracts.
Genetic counseling
Transmission is autosomal recessive.

                            Last update: 
                            April 2008
Leukoencephalopathy with calcifications and cysts (ORPHA:542310)
A rare genetic cerebral small vessel disease characterized by leukoencephalopathy and cerebral calcification and cysts due to diffuse cerebral microangiopathy resulting in microcystic and macrocystic parenchymal degeneration. The condition can present at any age from early childhood to late adulthood and manifests as a progressive cerebral degeneration. Symptoms are variable, but restricted to the central nervous systems, and include, among others, slowing of cognitive performance, seizures, and movement disorder with a combination of pyramidal, extrapyramidal, and cerebellar features.
Leukoencephalopathy with mild cerebellar ataxia and white matter edema (ORPHA:363540)
A rare neurologic disease characterized by a specific pattern of white matter abnormalities on brain imaging (magnetic resonance imaging, MRI), as well as mild ataxia, headaches, mild visual impairment, learning difficulties and cases of male infertility.
Leukoencephalopathy-dystonia-motor neuropathy syndrome (ORPHA:163684)
Leukoencephalopathy-dystonia-motor neuropathy syndrome is a peroxisomal neurodegenerative disorder characterized by spasmodic torticollis, dystonic head tremor, intention tremor, nystagmus, hyposmia, and hypergonadotrophic hypogonadism with azoospermia. Slight cerebellar signs (left-sided intention tremor, balance and gait impairment) are also noted. Magnetic resonance imaging (MRI) shows bilateral hyperintense signals in the thalamus, butterfly-like lesions in the pons, and lesions in the occipital region, whereas nerve conduction studies of the lower extremities shows a predominantly motor and slight sensory neuropathy.
Leukoencephalopathy-palmoplantar keratoderma syndrome (ORPHA:2386)
Leukoencephalopathy-palmoplantar keratoderma syndrome is a rare, genetic epidermal disease characterized by early childhood-onset of punctate palmoplantar keratoderma in association with adult-onset leukoencephalopathy manifested by progressive tetrapyramidal syndrome and cognitive deterioration.
Leukoencephalopathy-spondyloepimetaphyseal dysplasia syndrome (ORPHA:83629)
A rare genetic neurological disorder characterized by the association of hypomyelinating leukodystrophy with spondylometaphyseal dysplasia. Patients present in infancy with absent or delayed ability to walk independently, slowly progressive motor deterioration, spasticity, ataxia, proximal weakness, and joint contractures. Additional manifestations include mild cognitive impairment, short stature, scoliosis, enlarged and deformed joints, dysarthria, nystagmus, visual defects, and mildly dysmorphic features, among others. Mode of inheritance is X-linked recessive.