TaoMedAI/RareMedData huggingface dataset:
Multiple congenital anomalies-hypotonia-seizures syndrome type 2 (ORPHA:300496)
A rare, genetic, lethal, neurometabolic malformation syndrome characterized by multiple, variable, congenital cardiac (systolic murmur, atrial septal defect), urinary (duplicated collecting system, vesicoureteral reflux) and central nervous system (thin corpus callosum, cerebellar hypoplasia) malformations associated with neonatal hypotonia, early-onset epileptic encephalopathy, and myoclonic seizures. Craniofacial dysmorphism (prominent occiput, enlarged fontanel, fused metopic suture, upslanted palpebral fissures, overfolded helix, depressed nasal bridge, anteverted nose, malar flattening, microstomy with downturned corners, Pierre-Robin sequence, high arched palate, short neck) and other manifestations (joint contractures, hyperreflexia, dysplastic nails, developmental delay) are also observed.
Multiple congenital anomalies-hypotonia-seizures syndrome (ORPHA:280633)
A rare, genetic, multiple congenital anomalies/dysmorphic syndrome characterized by severe global developmental delay, hypotonia, and early-onset seizures, associated with multiple congenital anomalies, such as cardiac (e.g. patent foramen ovale, atrial septal defect, patent ductus arteriosus), genitourinary (i.e. hydrocele, renal collecting system dilatation, hydroureter, hydronephrosis, hypertrophic trabecular urinary bladder) and gastrointestinal abnormalities (including gastroesophageal reflux, anal stenosis, imperforate anus, ano-vestibular fistula), as well as facial dysmorphism which includes coarse facies, a prominent occiput, bitemporal narrowing, epicanthal folds, hypertelorism, nystagmus/strabismus/wandering eyes, low-set, large ears with auricle abnormalities, depressed nasal bridge, upturned nose, long philtrum, large, open mouth with thin lips, high-arched palate, and micro/retrognathia.
Multiple endocrine neoplasia type 2A (ORPHA:247698)
A form of multiple endocrine neoplasia type 2 (MEN2) syndrome characterized by medullary thyroid carcinoma in association with pheochromocytoma (one or both adrenal glands can be affected) and/or primary hyperparathyroidism (caused by parathyroid adenoma). Onset is typically later than in MEN2B, before 35 years of age. Diarrhea is the most frequent systemic symptom. Patients can develop Hirschsprung disease and, less frequently, cutaneous lichen amyloidosis or excessive production of adrenocorticotropic hormone.
Multiple endocrine neoplasia type 2B (ORPHA:247709)
A rare form of multiple endocrine neoplasia type 2 (MEN2) syndrome characterized by aggressive medullary thyroid carcinoma in association with other endocrine tumors, notably pheochromocytoma (one or both adrenal glands can be affected). Onset is typically in infancy or childhood and patients often have a typical facies (mucosal neuromas of the lips and tongue, and bumpy lips), ophthalmologic abnormalities (alacrima in infancy, thickened and everted eyelids, mild ptosis, and prominent corneal nerves), skeletal anomalies (marfanoid body habitus, narrow long facies, pes cavus, pectus excavatum, high-arched palate, scoliosis, hyperextensible joints and slipped capital femoral epiphyses), and a generalized ganglioneuromatosis throughout the aerodigestive tract. Chronic constipation, abdominal distension, diarrhea, or megacolon at birth are often the initial manifestations.
Multiple endocrine neoplasia type 4 (ORPHA:276152)
Multiple endocrine neoplasia type 4 (MEN4) is a very rare form of MEN (see this term), an inherited cancer syndrome, characterized by parathyroid and anterior pituitary tumors, possibly associated with adrenal, renal, and reproductive organ tumors.
Epidemiology
The prevalence of multiple endocrine neoplasia type 4 is unknown, but the syndrome is very rare. To date, 12 index cases have been reported. Prevalence is thought to be less than 1/million.
Clinical description
MEN4 is a recently described MEN-like syndrome similar to MEN1 (see this term). Age of onset of tumors is variable. Patients have been reported to develop parathyroid tumors from fourth decade of life and pituitary tumors from the third decade. Affected patients develop parathyroid tumor with associated primary hyperparathyroidism (81%) and anterior pituitary tumors (42%). In MEN4 patients, various types of pituitary adenoma have been reported: Cushing disease, somatotropic adenoma, prolactinoma, and non-functioning pituitary adenoma (see these terms). Cases of gastric and bronchial carcinoid tumor or Zollinger-Ellison syndrome (see this term) have also been reported. Other associated tumors include reproductive organ tumors, peripheral neuroendocrine tumor of cervix uteri (see this term), and adrenal or renal tumors.
Etiology
MEN4 is caused by heterozygous inactivating mutations in the CDKN1B gene (12p13.1-p12) encoding p27, a cyclin-dependent kinase inhibitor that acts as a negative regulator of cell cycle progression. In MEN4, unlike in MEN1, CDKN1B acts as a non-conventional oncosuppressor gene and no loss of heterozygosity has been reported. The exact MEN4 tumorigenesis molecular mechanisms remain to be elucidated but it is suspected that the mutated allele could be responsible for the reduction of p27 protein localized in the nucleus and, thus, able to exert its role of negative regulator of cell cycle progression and cell growth.
Genetic counseling
Most cases are the result of autosomal dominant inheritance. Some cases of sporadic de novo occurrence are however reported. Genetic counseling should be provided to affected individuals and their families.

                            Last update: 
                            April 2015


                            - Expert reviewer(s): 
                            Pr Maria Luisa BRANDI
Multiple endocrine neoplasia (ORPHA:276161)
Multiple endocrine neoplasia (MEN) is a group of rare inherited cancer syndromes characterized by the development of two or more endocrine gland tumors, sometimes with tumor development in other tissues or organs.
Epidemiology
The overall prevalence and incidence of MEN are not known. The prevalence of MEN1 is estimated to be approximately 1/10,000 to 1/30,000, while the total prevalence of MEN2 variants is approximately 1/35,000. MEN4 is extremely rare. The incidence of MEN1 has been estimated from random postmortem studies to be 0.25%, and to be 1-18% in patients with primary hyperparathyroidism, 16 to 38% in patients with gastrinomas, and less than 3% in patients with pituitary tumors.
Clinical description
Multiple endocrine neoplasia syndromes can develop in patients of all ages: from infants to elderly patients over 70 years of age. Manifestations vary depending on the affected endocrine glands. There are three types of MEN (multiple endocrine neoplasia types 1, 2, and 4; see these terms) based on the underlying genetic abnormalities, the endocrine glands involved and the clinical manifestations. Each type includes a different combination of pituitary, pancreatic, parathyroid, medullary, thyroid, and adrenal tumors. MEN1 is characterized by parathyroid, pituitary gland, and pancreatic tumors. MEN2 is divided into two subtypes: MEN2A characterized by medullary thyroid carcinoma (see this term) in combination with pheochromocytoma (see this term) and primary mild hyperparathyroidism; and MEN2B (formerly MEN3), a rare form, involving medullary thyroid carcinoma, pheochromocytoma, mucosal ganglioneuromas and marfanoid habitus. MEN4 involves the development of parathyroid and anterior pituitary tumors.
Etiology
MEN1 is caused by inactivating mutations in the MEN1 gene (11q13), and in some patients by mutations in the cyclin-dependent kinase inhibitor genes (CDKN1A, CDKN2B, CDKN2C). MEN2A and MEN2B are due to activating mutations in the RET gene (10q11.2), and MEN4 to inactivating mutations in the CDKN1B gene (12p13.1-p12). Patients with MEN1-like phenotypes (primary hyperparathyroidism associated with various tumors and lesions of the pituitary gland, pancreas, and duodenum) have also been found to have inactivating germline heterozygote mutation in CDKN1B.
Genetic counseling
MEN follows an autosomal dominant pattern of inheritance and some sporadic cases are reported. First-degree relatives have a 50% risk of developing the disorder, making appropriate genetic counseling very important in affected families. Biochemical and genetic screening may be suggested to family members.

                            Last update: 
                            April 2015


                            - Expert reviewer(s): 
                            Pr Maria Luisa BRANDI
Multiple epiphyseal dysplasia due to collagen 9 anomaly (ORPHA:166002)
Multiple epiphyseal dysplasia due to collagen 9 anomaly is a rare primary bone dysplasia disorder characterized by normal or mild short stature, early-onset pain and/or stiffness of the joints (mainly affecting knees but also elbows, wrists, ankles and fingers, with relative sparing of the hips) and early degenerative joint disease. Other skeletal anomalies (incl. varus or valgus deformities, osteochondritis dissecans, abnormal carpal shape, free articular bodies) and mild myopathy have also been reported.
Multiple epiphyseal dysplasia type 1 (ORPHA:93308)
Multiple epiphyseal dysplasia type 1 (MED 1) is a form of multiple epiphyseal dysplasia that is characterized by normal or mild short stature, pain in the hips and/or knees, progressive deformity of extremities and early-onset osteoarthrosis. Specific features to MED 1 include a more pronounced involvement of hip joints and gait abnormality and a shorter adult height. MED1 is allelic to pseudoachondroplasia with which it shares clinical and radiological features. The disease follows an autosomal dominant mode of transmission.
Multiple epiphyseal dysplasia type 4 (ORPHA:93307)
Multiple epiphyseal dysplasia type 4 is a multiple epiphyseal dysplasia with a late-childhood onset, characterized by joint pain involving hips, knees, wrists, and fingers with occasional limitation of joint movements, deformity of hands, feet, and knees (club foot, clinodactyly, brachydactyly), scoliosis and slightly reduced adult height. Radiographs display flat epiphyses with early arthritis of the hip, and double-layered patella. Multiple epiphyseal dysplasia type 4 follows an autosomal recessive mode of transmission. The disease is allelic to diastrophic dwarfism, atelosteogenesis type 2 and achondrogenesis type 1B with whom it forms a clinical continuum.
Multiple epiphyseal dysplasia type 5 (ORPHA:93311)
Multiple epiphyseal dysplasia type 5 is a multiple epiphyseal dysplasia characterized by an early-onset of pain and stiffness (involving knee and hip), progressive deformity of the extremities and precocious osteoarthritis associated with delayed and irregular ossification of epiphyses. Features specific to multiple epiphyseal dysplasia, type 5 include normal stature and lesser incidence of gait abnormalities. Radiographs reveal epiphyseal and metaphyseal irregularities. Multiple epiphyseal dysplasia type 5 follows an autosomal dominant mode of transmission.
Multiple epiphyseal dysplasia, Lowry type (ORPHA:166016)
Multiple epiphyseal dysplasia, Lowry type is a rare primary bone dysplasia characterized by small, flat epiphyses (esp. the capital femoral epiphyses), rhizomelic shortening of limbs, cleft of secondary palate, micrognathia, mild joint contractures and facial dysmorphism (incl. mildly upward-slanting palpebral fissures, hypertelorism, broad nasal tip). Additionally reported features include scoliosis, genu valgum, mild pectus excavatum, platyspondyly, dislocated radial heads, brachydactyly, hypoplastic fibulae and talipes equinovarus.
Multiple epiphyseal dysplasia-macrocephaly-facial dysmorphism syndrome (ORPHA:166024)
A rare primary bone dysplasia characterized by the association of multiple epiphyseal dysplasia with macrocephaly and dysmorphic facial features (such as frontal bossing, hypertelorism, flat malar region, low-set ears, and short neck). Patients are of normal stature and present with joint swelling and genu valgum. Additional reported manifestations include clinodactyly, spindle-shaped fingers, and pectus excavatum.
Multiple epiphyseal dysplasia-miniepiphyses syndrome (ORPHA:166032)
Multiple epiphyseal dysplasia, with miniepiphyses is a rare primary bone dysplasia disorder characterized by strikingly small secondary ossification centers (mini-epiphyses) in all or only some joints, resulting in severe bone dysplasia of the proximal femoral heads. Short stature, increased lumbar lordosis, genua vara and generalized joint laxity have also been reported.
Multiple epiphyseal dysplasia-severe proximal femoral dysplasia syndrome (ORPHA:166029)
Multiple epiphyseal dysplasia, with severe proximal femoral dysplasia is a rare primary bone dysplasia characterized by severe, early-onset dysplasia of the proximal femurs, with almost complete absence of the secondary ossification centers and abnormal development of the femoral necks (short and broad with irregular metaphyses). It is associated with gait abnormality, mild short stature, arthralgia, joint stiffness with limited mobility of the hips and irregular acetabula, and hip and knee pain. Coxa vara and mild spinal changes are also associated.
Multiple epiphyseal dysplasia (ORPHA:251)
A rare group of primary bone dysplasia disorders characterized by the association of epiphyseal anomalies of long bones causing joint pain early in life, recurrent osteochondritis and early arthrosis. This group contains an heterogeneous group of diseases with variable expression. Common reported clinical signs include waddling gait and pain at onset, and moderate short stature. Some forms are mainly limited to the femoral epiphyses, while several other syndromes are characterized by the association of multiple epiphyseal dysplasia with other clinical manifestations such as myopia, deafness and facial dysmorphism. Diagnosis relies on identification of the radiological features.
Multiple intestinal atresia (ORPHA:2300)
Multiple intestinal atresia is a rare form of intestinal atresia characterized by the presence of numerous atresic segments in the small bowel (duodenum) or large bowel and leading to symptoms of intestinal obstruction: vomiting, abdominal bloating and inability to pass meconium in newborns.
Multiple mitochondrial dysfunctions syndrome type 1 (ORPHA:401869)
A rare mitochondrial disease characterized by failure to thrive, infantile encephalopathy, muscular hypotonia, global developmental delay and regression, pulmonary arterial hypertension, episodes of apnea and bradycardia, respiratory failure, hyperglycinemia, and lactic acidosis. Hypertrophic or dilated cardiomyopathy have also been reported. Brain imaging may show leukoencephalopathy involving variable regions. The disease is typically fatal in early infancy.
Multiple mitochondrial dysfunctions syndrome type 2 (ORPHA:401874)
A rare mitochondrial disease characterized by infantile onset of severe regression after a period of normal development, epileptic encephalopathy, hypotonia, movement disorder, cardiomyopathy, hyperglycinemia, and lactic acidosis. Optic atrophy may also be present. Brain imaging findings are highly variable and include white matter abnormalities. The disease is typically fatal in infancy.
Multiple mitochondrial dysfunctions syndrome type 3 (ORPHA:363424)
A rare neurometabolic disease, due to a lipoic acid biosynthesis defect, with a highly variable phenotype, typically characterized by early-onset acute or subacute developmental delay or regression frequently associated with feeding difficulties. Clinical severity is variable and may range from mild cases which present a later onset with slow neurological deterioration and general improvement over time to severe cases with clinical signs since birth and leading to early death. Associated manifestations include hypotonia, vision loss, respiratory failure, seizures, and intellectual disability. Brain magnetic resonance imaging frequently shows cavitating leukoencephalopathy with lesions in the periventricular/central white matter and parieto-occiîtal lobes.
Multiple mitochondrial dysfunctions syndrome type 4 (ORPHA:457406)
A rare, severe, genetic, neurometabolic disease characterized by infantile-onset of progressive neurodevelopmental regression, optic atrophy with nystagmus and diffuse white matter disease. Affected individuals usually have central hypotonia that progresses to limb spasticity and hyperreflexia, eventually resulting in a vegetative state. Recurrent chest infections are frequently associated and seizures (usually generalized tonic-clonic) may occasionally be observed. Brain magnetic resonance imaging shows diffuse bilateral symmetric abnormalities in the cerebral periventricular white matter, with variable lesions in other areas but sparing the basal ganglia.
Multiple mitochondrial dysfunctions syndrome type 5 (ORPHA:569274)
A rare mitochondrial disease characterized by early infantile onset of progressive neurological deterioration with seizures, spasticity, and lack of psychomotor development. Brain imaging shows severe leukodystrophy and abnormalities of neuronal migration. Lactic acidosis is common. The disease is usually fatal in early childhood.
Multiple mitochondrial dysfunctions syndrome type 6 (ORPHA:569290)
A rare mitochondrial disease characterized by onset of episodic developmental regression in the first year of life, often in the setting of febrile illnesses, as well as hypotonia and seizures or refractory epileptic encephalopathy. Other observed features include ataxia, dystonia, or optic atrophy, among others. Patients do not achieve independent ambulation or meaningful speech. Brain imaging may show progressive cerebellar or diffuse atrophy and signal abnormalities of the basal ganglia. Serum lactate is often elevated.
Multiple mitochondrial dysfunctions syndrome (ORPHA:289573)
Multiple mitochondrial dysfunctions syndrome describes a group of rare inborn errors of energy metabolism due to defects in mitochondrial [4Fe-4S] protein assembly. Patients present with a neonatal/infancy onset of metabolic lactic acidosis (that may be associated with hyperglycinemia and other abnormal metabolic testing results), muscular hypotonia, absence of psychomotor development or developmental regression, as well as abnormal neuroimaging findings (including leukodystrophy, brain developmental defects, white matter abnormalities, cerebral atrophy), and other variable clinical features (e.g., optic atrophy, cardiomyopathy, pulmonary hypertension, seizures, and dysmorphic features). Early fatal outcome is usual.
Multiple myeloma (ORPHA:29073)
Multiple myeloma (MM) is a malignant tumor of plasma cell characterized by overproduction of abnormal plasma cells in the bone marrow and skeletal destruction. The clinical features are bone pain, renal impairment, immunodeficiency, anemia and presence of abnormal immunoglobulins (Ig).
Multiple paragangliomas associated with polycythemia (ORPHA:324299)
A rare, endocrine disease characterized by early onset of polycythemia, and later occuring multiple parangliomas. Clinical presentation includes hypertension, headaches, fatigue, nausea, anxiety, and high concentration of red blood cells, leading to increased risk of stroke and pulmonary thromboembolism.
Multiple pterygium syndrome (ORPHA:294060)
A group of rare genetic disorders characterized by the presence of joint contractures and multiple soft tissue webs (pterygia) across the neck and various joints, as well as typical facial appearance and a variety of other congenital anomalies. Both lethal (lethal and X-linked lethal multiple pterygium syndrome) and non-lethal (autosomal recessive and autosomal dominant multiple pterygium syndrome) forms occur.
Multiple pterygium-malignant hyperthermia syndrome (ORPHA:2215)
An extremely rare arthrogryposis syndrome, described in only two pairs of siblings from two unrelated families to date, and characterized by the association of arthrogryposis, congenital torticollis, dysmorphic facial features (i.e. asymmetry of the face, myopathic facial movements, ptosis, posteriorly rotated ears, cleft palate), progressive scoliosis and episodes of malignant hyperthermia. There have been no further descriptions in the literature since 1988.
Multiple sclerosis-ichthyosis-factor VIII deficiency syndrome (ORPHA:3151)
Multiple sclerosis-ichthyosis-factor VIII deficiency syndrome is characterized by the association of multiple sclerosis with lamellar ichthyosis (see this term) and hematological anomalies (beta thalassemia minor and a quantitative deficit of factor VIII-von Willebrand complex). Other clinical manifestations may include eye involvement (optic atrophy, diplopia), neuromuscular involvement (ataxia, pyramidal syndrome, gait disturbance) and sensory disorder. There have been no further descriptions in the literature since 1992.
Multiple self-healing squamous epithelioma (ORPHA:65748)
Multiple self-healing squamous epithelioma (also known as Ferguson-Smith disease (FSD)) is a rare inherited skin cancer syndrome characterized by the development of multiple locally invasive skin tumors resembling keratoacanthomas of the face and limbs which usually heal spontaneously after several months leaving pitted scars.
Epidemiology
The prevalence is unknown but to date over 100 cases have been reported with several large affected families originating in western Scotland.
Clinical description
Tumors typically start as a reddish macule which becomes papular, enlarged and ulcerated. As the tumor involutes, a horny plug forms that falls out leaving a deep pit with irregular, over-hanging edges. Tumors have a predilection for sun-exposed areas, especially nose, ears and circumoral regions. Lesions on the limbs are often larger and leave flat scars. The trunk is seldom affected. Lifetime tumor numbers range from a few to over a hundred. The age of onset of a first tumor is very variable ranging from 8 to over 70 years (median 28 years). Histological assessment of these tumors reveals well differentiated squamous carcinomas. Treatment with radiotherapy must be avoided because more numerous, more invasive tumors arise in previously irradiated skin.
Etiology
FSD may be due to loss of function mutations in the gene TGFBR1 (9q22) which encodes a transmembrane serine/threonine kinase receptor involved in TGF-β signaling. Mutations in the gene TGFBR1 are also found in Loeys-Dietz syndrome (LDS; see this term) but the spectrum of TGFBR1 mutations differs and the mutations found in most FSD families have not been associated with a predisposition to aortic aneurysm or other developmental defects that occur in LDS. It has been suggested that FSD is an oligogenic trait. Inherited permissive variants at TGFBR1 and a second, as yet unidentified, linked locus on the long arm of chromosome 9 appear to be required for tumor development. 90% of TGFBR1 mutation carriers in affected families developed the condition by age 60. Palmar and plantar skin are not affected suggesting that the tumors arise from hair follicles.
Genetic counseling
Although FSD is likely to be an oligogenic trait, the condition is inherited in an autosomal dominant manner because the TGFBR1 mutations and predisposing variants at the second linked locus are usually inherited together in affected families.

                            Last update: 
                            February 2015


                            - Expert reviewer(s): 
                            Pr Malcolm FERGUSON-SMITH  - Dr David GOUDIE
Multiple synostoses syndrome (ORPHA:3237)
Multiple synostoses syndrome (MSS) is a rare developmental bone disorder characterized by proximal symphalangism of the fingers and/or toes often associated with fusion of carpal and tarsal, humeroradial, and cervical spine joints.