TaoMedAI/RareMedData huggingface dataset:
Laminin subunit alpha 2-related congenital muscular dystrophy (ORPHA:258)
Congenital muscular dystrophy type 1A (MCD1A) belongs to a group of neuromuscular disorders with onset at birth or infancy characterized by hypotonia, muscle weakness and muscle wasting.
Epidemiology
MCD1A represents 30-40% of congenital muscular dystrophies, with some regional variation. Prevalence is estimated at 1/30,000.
Clinical description
The disease presents at birth or in the first few months of life with hypotonia and muscle weakness in the limbs and trunk. Respiratory and feeding disorders can also occur. Motor development is delayed and limited (sitting or standing is only possible with help). Infants present with early rigidity of the vertebral column, scoliosis, and respiratory insufficiency. There is facial involvement with a typical elongated myopathic face and ocular ophthalmoplegia disorders can appear later. Epileptic attacks are possible, although they occur in less than a third of patients. Intellectual development is normal.
Etiology
MCD1A is caused by mutations in the LAMA2 gene coding for the alpha-2 laminin chain.
Diagnostic methods
Diagnosis is based on muscular biopsy, as merosin deficiency can be detected in the muscle and skin. MRI reveals diffuse abnormalities in brain white matter, typically sparing the corpus callosum, capsula interna and cerebellum. In the initial phase of the disease there is a four-fold increase in levels of serous creatine kinase.
Differential diagnosis
Differential diagnoses include other forms of congenital muscular dystrophy, linked particularly with glycosylation and alpha-dystroglycan anomalies, as well as congenital structural myopathies (central core disease, multi-minicore myopathy, centronuclear myopathy), of which the causative genes have been identified in the majority of cases (see these terms).
Antenatal diagnosis
Prenatal diagnosis is possible in the ninth week by chorionic villus sampling for evidence of merosin deficiency, and by evidence of mutation in the LAMA2 gene.
Genetic counseling
Transmission is autosomal recessive. Genetic counseling should be offered to families.
Management and treatment
Treatment is symptomatic. It consists of a multidisciplinary approach, including physiotherapists, occupational therapists and speech-language therapists, with the objective of optimizing each patient's abilities. Seizures or other neurological complications require specific treatment.
Prognosis
The prognosis of these muscular dystrophies is very severe as a large proportion of affected children do not reach adolescence. Currently, the prognosis can only be improved by attentive multidisciplinary (particularly orthopedic and respiratory) management.

                            Last update: 
                            April 2009


                            - Expert reviewer(s): 
                            Pr Michel FARDEAU
Laminin subunit alpha 2-related limb-girdle muscular dystrophy R23 (ORPHA:565837)
A rare autosomal recessive limb-girdle muscular dystrophy characterized by childhood to adult onset of slowly progressive limb girdle muscular weakness, often accompanied by calf hypertrophy, and moderately elevated creatine kinase levels. Patients remain ambulatory but may variably present mild intellectual disability, seizures, migraine, or cardiopulmonary involvement. Occurrence of dilated cardiomyopathy has been reported. Brain MRI typically shows hyperintensity in T2-weighted sequences. Muscle biopsy commonly reveals dystrophic features.
Langerhans cell sarcoma (ORPHA:86897)
A rare dendritic cell tumor characterized by an aggressive, high-grade neoplasm derived from Langerhans cells, most commonly extranodal and multifocal, involving the skin and underlying soft tissue, as well as lung, liver, spleen, and bone. Primary nodal involvement is seen in a minority of patients. Immune-phenotyping and the presence of Birbeck granules on ultrastructural examination reveal the Langerhans cell derivation of the neoplastic cells. Prognosis is generally poor.
Laron syndrome with immunodeficiency (ORPHA:220465)
This syndrome is characterized by severe growth retardation associated with immunodeficiency.
Epidemiology
Less than 10 cases have been described in literature.
Clinical description
The patients present typical clinical and biochemical features of Laron syndrome such as post-natal growth retardation, delayed bone age and facial dysmorphism (prominent forehead, hypoplastic nasal bridge), and low serum IGF-1 concentrations with normal or high GH concentrations. Immunodeficiency is characterized by moderate lymphopenia which leads to recurrent infections of the skin and respiratory tract. Severe chronic lung disease, chronic diarrhea, juvenile idiopathic arthritis (see these terms), generalized eczema, pulmonary infections and respiratory distress have already been described.
Etiology
The syndrome is due to mutation in the signal transducer and activator of transcription 5b gene (STAT5b). Transmission is autosomal recessive. There have been reports of STAT5b mutations resulting in Laron symptoms but not associated with immunodeficiency.

                            Last update: 
                            February 2010


                            - Expert reviewer(s): 
                            Pr Juliane LEGER
Larsen syndrome (ORPHA:503)
An orofacial clefting syndrome characterized by congenital dislocation of large joints, foot deformities, cervical spine dysplasia, scoliosis, spatula-shaped distal phalanges and distinctive craniofacial abnormalities, including cleft palate.
Epidemiology
Larsen syndrome (LS) birth prevalence is estimated to be less than 1 in 100,000 in Europe.
Clinical description
Primary clinical characteristics of LS are congenital dislocations of hip, knee and elbow joints with equinovarus or equinovalgus foot deformities (club feet). Other frequent manifestations include spinal deformities such as scoliosis and cervical spine kyphosis, sometimes associated with cervical myelopathy and short, broad, spatula-shaped distal phalanges with the thumb almost always affected. Recurrent craniofacial abnormalities include a prominent forehead, depressed nasal bridge, flattened midface and ocular hypertelorism. Midline cleft palate and conductive hearing loss have also commonly been reported.
Etiology
The syndrome is due to missense mutations or small in frame deletions in the FLNB gene (localized to 3p14.3) that encodes cytoskeletal protein filamin B.
Diagnostic methods
Diagnosis is established by clinical assessment, and skeletal X-rays displaying, amongst other factors, supernumerary carpal and tarsal bone ossification centers and is confirmed by genetic testing.
Differential diagnosis
Differential diagnosis includes other more severe and lethal FLNB-related disorders: atelosteogenesis type I, atelosteogenesis type III and boomerang dysplasia as well as otopalatodigital syndrome type I and spondyloepiphyseal dysplasia, CHST3 type; chondrodysplasia with joint dislocations, gPAPP type; Larsen-like syndrome, B3GAT3 type; Reunion island's Larsen syndrome and Desbuquois syndrome.
Antenatal diagnosis
Prenatal diagnosis is available for those with a family history of LS.
Genetic counseling
LS is transmitted in an autosomal dominant manner. The autosomal recessive cases reported in the past may perhaps correspond to parental germline mosaicism, but are more likely to represent more recently defined recessive syndromes with similar but still distinct presentations. Genetic counseling should be proposed to individuals having the disease causing mutation informing them that there is 50% risk of passing the mutation to offspring.
Management and treatment
Management should be adapted to each patient and may involve orthopedic treatment and monitoring, surgical procedures, especially for hip dislocation, and physiotherapy. In case of hearing loss, a multidisciplinary team with pediatric expertise is recommended. It is essential that all infants with a clinical diagnosis of LS have their cervical spine evaluated as soon as practicable after birth to exclude life threatening cervical spine instability.
Prognosis
LS does not affect life expectancy.

                            Last update: 
                            December 2019


                            - Expert reviewer(s): 
                            Pr Stephen ROBERTSON  - Dr Emma WADE
Larsen-like osseous dysplasia-short stature syndrome (ORPHA:2370)
Larsen-like osseous dysplasia-short stature syndrome is a rare primary bone dysplasia characterized by a Larsen-like phenotype including multiple, congenital, large joint dislocations, craniofacial abnormalities (i.e. macrocephaly, flat occiput, prominent forehead, hypertelorism, low-set, malformed ears, flat nose, cleft palate), spinal abnormalities, cylindrical fingers, and talipes equinovarus, as well as growth retardation (resulting in short stature) and delayed bone age. Other reported clinical manifestations include severe developmental delay, hypotonia, clinodactyly, congenital heart defect and renal dysplasia.
Larsen-like syndrome, B3GAT3 type (ORPHA:284139)
Larsen-like syndrome, B3GAT3 type is a rare, genetic, primary bone dysplasia characterized by laxity, dislocations and contractures of the joints, short stature, foot deformities (e.g. clubfeet), broad tips of fingers and toes, short neck, dysmorphic facial features (hypertelorism, downslanting palpebral fissures, upturned nose with anteverted nares, high arched palate) and various cardiac malformations. Severe disease is associated with multiple fractures, osteopenia, arachnodactyly and blue sclerae. A broad spectrum of additional features, including scoliosis, radio-ulnar synostosis, mild developmental delay, and various eye disorders (glaucoma, amblyopia, hyperopia, astigmatism, ptosis), are also reported.
Laryngeal abductor paralysis-intellectual disability syndrome (ORPHA:2375)
A rare X-linked syndromic intellectual disability characterized by congenital and permanent vocal cord paralysis causing severe congenital laryngeal stridor, associated with intellectual disability in male patients. Other presenting symptoms may include weak cry, cough, cyanosis, neonatal asphyxia, feeding difficulty, aspiration, and bronchiectasis. Microcephaly, tone abnormalities, visual and hearing impairment may also be associated features.
Laryngeal neuroendocrine tumor (ORPHA:100083)
A rare head and neck tumor characterized by an epithelial neoplasm with evidence of neuroendocrine differentiation, typically located in the supraglottic larynx. The tumor can be well, moderately, or poorly differentiated, the latter group being subdivided into small cell or large cell neuroendocrine carcinomas. There is a strong association with tobacco use. Patients present with hoarseness, dysphagia, sore throat, airway obstruction, hemoptysis, and rarely a paraneoplastic syndrome due to aberrant hormone production. Poorly differentiated tumors are highly aggressive with high rates of regional and distant metastasis.
Laryngo-onycho-cutaneous syndrome (ORPHA:2407)
LOC syndrome is a subtype of junctional epidermolysis bullosa (JEB, see this term) characterized by an altered cry in the neonatal period and by aberrant production of granulation tissue in particular affecting the upper airway tract, conjunctiva and periungual/subungual sites.
Epidemiology
Prevalence is unknown. Fewer than 50 cases have been reported to date, mostly in consanguineous families from the Punjabi region of Pakistan and India.
Clinical description
The condition is present at birth. Characteristic cutaneous findings are transient blisters leaving slowly healing erosions with exuberant granulation tissue formation, mainly localized to the head and neck, hands, feet, elbows and knees. Extracutaneous manifestations are always observed: the progressive laryngeal involvement frequently leads to fatal respiratory obstruction in infancy, and the chronic conjunctival lesions cause symblepharon formation, and also total palpebral occlusion and blindness. Enamel hypoplasia is also always present and nail dystrophies are common.
Etiology
The condition is associated with mutations in the alpha-3 chain of laminin-332 (LAMA3).
Genetic counseling
LOC syndrome follows an autosomal recessive pattern of inheritance.
Prognosis
Prognosis is poor.

                            Last update: 
                            October 2012


                            - Expert reviewer(s): 
                            Pr Giovanna ZAMBRUNO
Laryngocele (ORPHA:2372)
A rare congenital laryngeal anomaly characterized by an abnormal dilation of the laryngeal saccule that is filled with air, maintains communication with the laryngeal lumen, and is either confined to the false vocal fold or extends upward, protruding through the thyrohyoid membrane to the neck. Symptoms may include cough, hoarseness, stridor, sore throat and uni- or bilateral swelling of the neck. Blockage of the laryngocele neck can result isn laryngomucocele, and forms laryngopyocele when infected.
Laryngotracheoesophageal cleft type 0 (ORPHA:280205)
Laryngo-tracheo-esophageal cleft (LC) type 0 is a congenital respiratory tract anomaly characterized by a submucosal laryngo-tracheo-esophageal cleft with minor symptoms or an asymptomatic course.
Epidemiology
Prevalence of this form of LC is difficult to ascertain because of the mild or asymptomatic nature of the condition, but it is thought to be rare.
Clinical description
Subjects with type 0 LC may have no obvious symptoms or mild symptoms such as occasional aspirations. Syndromic associations may be present.
Etiology
The causes underlying development of this anomaly are unknown.
Diagnostic methods
The anomaly is often detected during endoscopy indicated for other reasons.
Management and treatment
No specific treatment is required.

                            Last update: 
                            November 2011


                            - Expert reviewer(s): 
                            Pr Noël GARABEDIAN  - Pr Nicolas LEBOULANGER
Laryngotracheoesophageal cleft type 1 (ORPHA:93938)
A congenital respiratory tract anomaly characterized by a supraglottic, interarytenoid cleft above the vocal folds with moderate respiratory symptoms.
Epidemiology
Prevalence of this form of LC is difficult to ascertain because of the moderate nature of the condition, but it is thought to be rare.
Clinical description
Clinical signs include stridor, a toneless or hoarse cry, swallowing disorders such as aspirations, cough, dyspnea, cyanosis during feeding and gastro-esophageal reflux.
Etiology
The causes underlying development of this anomaly are unknown.
Management and treatment
In children with mildly symptomatic type 1 LC, management includes maintaining adequate ventilation, feeding with thickened food, treatment of gastro-esophageal reflux, and maintaining a postprandial upright position. Children with moderate symptoms may also benefit from nasogastric tube feeding. Treatment initially involves conservative measures such as anti-reflux therapy, thickened feeds, and maneuvers during feeding to prevent aspiration. In cases of failure of a conservative approach, surgical correction of the cleft, using an endoscopic treatment approach, is recommended.

                            Last update: 
                            November 2011


                            - Expert reviewer(s): 
                            Pr Noël GARABEDIAN  - Pr Nicolas LEBOULANGER
Laryngotracheoesophageal cleft type 2 (ORPHA:93939)
A congenital respiratory tract anomaly characterized by a cleft extending below the vocal folds into the cricoid cartilage, with swallowing disorders and lung infections.
Epidemiology
Prevalence of this form of LC is unknown, but it is thought to be rare.
Clinical description
Patients most often have aspirations and severe respiratory and swallowing disorders. Dyspnea and stridor are also possible.
Etiology
The causes underlying development of this anomaly are unknown.
Management and treatment
Management includes anti-reflux treatment and nasogastric tube feeding. Treatment involves surgical correction of the cleft, often using an endoscopic treatment approach.

                            Last update: 
                            November 2011


                            - Expert reviewer(s): 
                            Pr Noël GARABEDIAN  - Pr Nicolas LEBOULANGER
Laryngotracheoesophageal cleft type 3 (ORPHA:93940)
A congenital respiratory tract anomaly characterized by a cleft extending through the cricoid cartilage, sometimes into the cervical trachea, with severe swallowing disorders, lung infections and pulmonary damage.
Epidemiology
Prevalence of this form of LC is unknown, but it is thought to be very rare. To date, about 30 cases have been reported in the literature. .
Clinical description
Patients have constant aspirations and severe respiratory and swallowing disorders with a high risk of pulmonary infection.
Etiology
The causes underlying development of this anomaly are unknown.
Management and treatment
Parenteral nutrition may be required temporarily in patients with high-grade LCs due to the high risk of aspirations. High-grade LCs often require a mid- to long-term gastrostomy, often with fundoplication. Treatment involves surgical correction of the cleft, often requiring an external approach.
Prognosis
The prognosis in this type of LC is poor.

                            Last update: 
                            November 2011


                            - Expert reviewer(s): 
                            Pr Noël GARABEDIAN  - Pr Nicolas LEBOULANGER
Laryngotracheoesophageal cleft type 4 (ORPHA:93941)
A serious congenital respiratory tract anomaly characterized by a cleft extending into the thoracic trachea and possibly down to the carina, with respiratory distress.
Epidemiology
Prevalence of this form of LC is difficult to ascertain because of the extremely poor prognosis and death before diagnosis, but it is thought to be very rare. Fewer than 20 cases have been reported in the literature to date.
Clinical description
Patients have constant aspirations and serious life-threatening respiratory and swallowing disorders, often associated with other severe cardiopulmonary malformations.
Etiology
The causes underlying development of this anomaly are unknown.
Management and treatment
Parenteral nutrition may be required temporarily in patients with high-grade LCs due to the high risk of aspirations. High-grade LCs often require a mid- to long-term gastrostomy, often with fundoplication. Gastric division with a proximal drainage tube and distal gastrotomy have also been proposed. Treatment involves surgical correction of the cleft, often requiring an external cervical and/or thoracic approach, sometimes with cardiopulmonary bypass.
Prognosis
The prognosis in this type of LC is very poor.

                            Last update: 
                            November 2011


                            - Expert reviewer(s): 
                            Pr Noël GARABEDIAN  - Pr Nicolas LEBOULANGER
Larynx atresia (ORPHA:1202)
A rare larynx anomaly characterized by complete absence of the laryngeal lumen resulting in congenital upper airway obstruction syndrome which, without fetal or neonatal intervention, is incompatible with life. Fetal sonography shows a dilated trachea, hyperechoic lungs, pleural effusion, minimal fetal abdominal ascites or hydrops, and amniotic fluid abnormalities.
Late-onset citrullinemia type I (ORPHA:247573)
A form of citrullinemia type I characterized clinically by adult onset of symptoms including variable hyperammonemia and less striking neurological findings which may include intense headache, scotomas, migraine-like episodes, ataxia, slurred speech, lethargy and drowsiness. Serious increased intracranial pressure may occur.
Late-onset distal myopathy, Markesbery-Griggs type (ORPHA:98912)
A rare, genetic, non-dystrophic myofibrillar myopathy disorder characterized by late-adult onset of distal and/or proximal limb muscle weakness with initial involvement of posterior lower leg muscles, medial gastrocnemius and soleus. Patients present with ankle weakness followed by weakness of finger and wrist extensors and later on of proximal muscles. Ambulation is usually preserved. Late-onset associated cardiomyopathy and/or neuropathy has been reported in a minority of cases.
Late-onset familial hypoaldosteronism (ORPHA:556037)
A rare form of familial hypoaldosteronism characterized by adult onset of subnormal plasma aldosterone with elevated plasma renin activity, hyperkalemia, metabolic acidosis, and hypotension. Signs and symptoms are typically mild, and affected individuals may be clinically asymptomatic and diagnosed only after biochemical screening.
Late-onset focal dermal elastosis (ORPHA:228227)
Late-onset focal dermal elastosis is a rare, acquired, dermis elastic tissue disorder characterized by a pseudoxanthoma elasticum-like papular eruption consisting of multiple, slowly progressive, asymptomatic, 2-5 mm, white to yellowish, non-follicular papules (that tend to form cobblestone plaques) predominantly distributed over the neck, axillae and flexural areas, with no systemic involvement. Skin biopsy reveals a focal increase of normal-appearing elastic tissue in the reticular dermis with no calcium deposits.
Late-onset isolated ACTH deficiency (ORPHA:199299)
Late-onset isolated ACTH deficiency is a rare, acquired, pituitary hormone deficiency characterized by secondary adrenal insufficiency, with normal secretion of anterior pituitary hormones, except for ACTH. Patients present with weakness, fatigue, weight loss, anorexia, vomiting/nausea, hypoglycemia, and abnormally low serum ACTH and cortisol levels. Association with autoimmune disease such as Hashimoto's thyroiditis has been described.
Late-onset junctional epidermolysis bullosa (ORPHA:79406)
A form of junctional epidermolysis bullosa characterized by onset in childhood or young adulthood of blistering that first occurs around nails, accompanied by nail dystrophy and shedding, and then affects the hands and feet and, to a lesser extent, the elbows, and knees. Lesions heal with atrophic scarring. Other manifestations include disappearance of dermatoglyphs and palmoplantar hyperhidrosis. Extracutaneous involvement is restricted to soft tissue abnormalities of the oral cavity and enamel defects with development of caries.
Late-onset localized junctional epidermolysis bullosa-intellectual disability syndrome (ORPHA:231556)
A rare junctional epidermolysis bullosa subtype characterized by late-onset blistering surrounded by erythema and localized on the anterior aspect of the lower legs, associated with dystrophic toenails, tooth enamel defects and mild to severe intellectual disability. Lens subluxation and mild facial dysmorphism (with short midface, prognatism and thin upper lip vermilion) are additional reported features. There have been no further descriptions in the literature since 1992.
Late-onset retinal degeneration (ORPHA:67042)
Late-onset retinal degeneration is an inherited retinal dystrophy characterized by delayed dark adaptation and nyctalopia and drusen deposits presenting in adulthood, followed by cone and rod degeneration that presents in the sixth decade of life, which leads to central vision loss. Anterior segment features such as peripupillary iris transillumination defects and abnormally long anterior zonular insertions are also observed. Choroidal neovascularization and glaucoma may occur in the late stages of the disease.
Lateral meningocele syndrome (ORPHA:2789)
A rare genetic neurological disorder characterized by multiple lateral meningoceles, distinctive facial dysmorphism (including hypertelorism, downslanting palpebral fissures, posteriorly rotated ears, micrognathia, and high, narrow palate, among others), and skeletal abnormalities (e. g. vertebral anomalies, wormian bones, short stature, and scoliosis). Multiple additional features may present, such as conductive hearing impairment, hypotonia, and connective tissue and urogenital abnormalities. Cognition is usually normal.