TaoMedAI/RareMedData huggingface dataset:
Melorheostosis with osteopoikilosis (ORPHA:1879)
Melorheostosis with osteopoikilosis is a rare sclerosing bone dysplasia, combining the clinical and radiological features of melorheostosis and osteopoikilosis (see these terms), that has been reported in some families with osteopoikilosis and that is characterized by a variable presentation of limb pain and deformities.
Epidemiology
Less than 5 families have been reported in the literature to date.
Clinical description
As osteopoikilosis is a benign, usually asymptomatic condition, the clinical signs are primarily those of melorheostosis that can manifest with joint contractures, pain, stiffness, limited joint functions, limb-length discrepancy and deformity.
Etiology
The combination of melorheostosis with osteopoikilosis may be an unusual complication of familial osteopoikilosis. Osteopoikilosis is caused by a germline mutation in the LEMD3 gene (12q14). A germline mutation in the LEMD3 gene may predispose individuals with osteopoikilosis to develop melorheostosis. However, the exact pathogenesis is currently unknown.
Genetic counseling
Osteopoikilosis is inherited autosomal dominantly. There are no reports of parent to child transmission of melorheostosis. Genetic counseling is possible.

                            Last update: 
                            November 2014


                            - Expert reviewer(s): 
                            Pr Geert MORTIER
MEND syndrome (ORPHA:401973)
A rare, genetic, syndromic, sterol biosynthesis disorder affecting males characterized by skin manifestations, including collodion membrane, ichthyosis, and patchy hypopigmentary lesions, associated with severe neurological involvement (e.g. intellectual disability, delayed psychomotor development, seizures, hydrocephalus, cerebellar/corpus callosum hypoplasia, Dandy-Walker malformation, hypotonia) and craniofacial dysmorphism (large anterior fontanelle, telecanthus, hypertelorism, microphthalmia, prominent nasal bridge, low-set ears, micrognathia, cleft palate). 2,3 toe syndactyly, polydactyly, and kyphosis, as well as ophthalmic, cardiac and urogenital anomalies may also be associated.
Mendelian susceptibility to mycobacterial diseases due to complete IFNgammaR2 deficiency (ORPHA:319547)
Mendelian susceptibily to mycobacterial diseases (MSMD) due to complete interferon gamma receptor 2 (IFN-gammaR2) deficiency is a genetic variant of MSMD (see this term) characterized by a complete deficiency in IFN-gammaR2, leading to an undetectable response to IFN-gamma, and consequently, to severe and often fatal infections with bacillus Calmette-Guérin (BCG) and other environmental mycobacteria (EM).
Epidemiology
The prevalence is unknown. Only ten children have been identified to date.
Clinical description
Severe and often fatal BCG and EM infections begin in early childhood (before the age of 3). The most common pathogens seen in patients include Mycobacterium fortuitum, Mycobacterium bovis BCG, Mycobacterium abscessus and Mycobacterium avium. Infections are disseminated and can involve soft tissue, bone marrow, lungs, skin, bones and lymph nodes. Infections manifest with fever, weight loss, hepatosplenomegaly and lymphadenopathies and can be fatal.
Etiology
This disease is caused by mutations in IFNGR2 on chromosome 21q22.1-22.2 which encodes the IFN-gamma receptor signal transducing chain, essential for IFN-gamma mediated immunity. Two clinically indistinguishable forms have been reportedly defined by the presence or absence of protein expression on the cell surface.
Diagnostic methods
Diagnosis is made by laboratory analysis. IFN-gamma, IL-12p40 and IL-12p70 levels can be measured by ELISA, after whole blood activation by BCG, BCG+IL-12 and BCG+IFN-gamma. Leukocytes and fibroblasts from patients with this immunodeficiency do not respond to IFN-gamma in vitro. Genetic testing reveals mutations in IFNGR2.
Differential diagnosis
Differential diagnosis includes the other variants of MSMD, especially complete IFN-gammaR1 deficiency (see this term). Chronic granulomatous disease, cystic fibrosis and severe combined immunodeficiency (see these terms) should also be excluded.
Antenatal diagnosis
As this disease is often fatal, antenatal diagnosis is offered to families with a known IFNGR2 mutation.
Genetic counseling
MSMD due to complete IFN-gammaR2 deficiency is inherited autosomal recessively and genetic counseling is recommended.
Management and treatment
The only curative option for MSMD due to complete IFN-gammaR2 deficiency is hematopoietic stem cell transplantation (HSCT). Due to a lack of specific receptors, IFN-gamma treatment is not indicated. BCG vaccination should be avoided in those with a known IFNGR2 mutation.
Prognosis
Prognosis is poor with most patients not living past 10 years of age.

                            Last update: 
                            February 2013


                            - Expert reviewer(s): 
                            Dr Jacinta BUSTAMANTE  - Pr Jean-Laurent CASANOVA
Mendelian susceptibility to mycobacterial diseases due to complete IL12B deficiency (ORPHA:319558)
Mendelian susceptibility to mycobacterial diseases (MSMD) due to complete interleukin-12 subunit beta (IL12B) deficiency is a genetic variant of MSMD (see this term) characterized by mild bacillus Calmette-Guérin (BCG) infections and recurrent Salmonella infections.
Epidemiology
The prevalence is unknown. Mutations have been found in 49 patients from 30 kindreds originating from India, Iran, Pakistan, Saudi Arabia and Tunisia.
Clinical description
The disease presents in early childhood. BCG is the most common infection encountered, usually after receiving the vaccination. Non-typhoidal Salmonella infections are also seen in half of all cases. A few other infections have been reported, including chronic mucocutaneous candidiasis (CMC), nocardiosis, and klebsiellosis. An incomplete clinical penetrance is observed in this immunodeficiency.
Etiology
MSMD due to complete IL12B deficiency is caused by homozygous mutations in the IL12B gene on chromosome 5q31.1-q33.1 which encodes for the IL-12p40 subunit. There are 9 different IL12B mutant alleles identified, including 2 small insertions, 3 small deletions, 2 splice site mutations, 1 large deletion and 1 nonsense mutation.
Diagnostic methods
Diagnosis is made by laboratory analysis. IFN-gamma, IL-12p40 and IL-12p70 levels can be measured by ELISA after whole blood activation by BCG, BCG+IL-12 and BCG+IFN-gamma. The patients lack detectable IL-12p70, IL-12p40 and produce low levels of IFN-gamma. Genetic testing reveals mutations in IL12B.
Differential diagnosis
Differential diagnoses include other genetic forms of MSMD, especially MSMD due to complete IL12RB1 deficiency (see this term).
Antenatal diagnosis
This immunodeficiency is not severe and antenatal diagnosis is not necessary.
Genetic counseling
MSMD due to complete IL12B deficiency is inherited in an autosomal recessive manner. Genetic counseling is possible for families where a IL12B mutation is known.
Management and treatment
BCG vaccination should be avoided in patients with this disease. Treatment involves prolonged antimicrobial therapy along with recombinant IFN-gamma to control infections, which is successful in most cases. Hematopoietic stem cell (HST) transplantation is not recommended.
Prognosis
Patients with this immunodeficiency usually have a good prognosis.

                            Last update: 
                            February 2013


                            - Expert reviewer(s): 
                            Dr Jacinta BUSTAMANTE  - Pr Jean-Laurent CASANOVA
Mendelian susceptibility to mycobacterial diseases due to complete IL12RB1 deficiency (ORPHA:319552)
Mendelian susceptibility to mycobacterial diseases (MSMD) due to complete interleukin-12 receptor subunit beta-1 (IL12RB1) deficiency is a genetic variant of MSMD (see this term) characterized by mild bacillus Calmette-Guérin (BCG) infections and recurrent Salmonella infections.
Epidemiology
The prevalence is unknown. Over 140 cases have been reported in the world.
Clinical description
Disease onset usually occurs in patients before the age of 12 with the appearance of BCG disease, usually after receiving the vaccination. Over half of patients with this variant experience an additional infection with non-typhoidal Salmonella. Severe tuberculosis caused by Mycobacterium tuberculosis has been reported in several unrelated patients, providing the first documented evidence of a mendelian predisposition to tuberculosis. Other infections with Paracoccidiodes brasiliensis, Leishmania and Klebsiella have been reported in a single patient. Some patients also suffer from Candida infections. Most genetically affected siblings of index cases are asymptomatic, indicating low penetrance for case definition phenotypes.
Etiology
MSMD due to complete IL12RB1 deficiency is caused by mutations in the IL12RB1 gene (19p13.1) subunit that encodes for the IL-12R-beta1 chain. These mutations impair the IL-12/IL-23 pathway essential for production of IFN-beta and the resulting immunity against Salmonella and BCG infections. Two clinically indistinguishable forms have been reported defined by the presence or absence of protein expression on the cell surface.
Diagnostic methods
Diagnosis is made by laboratory analysis. In general, there is no expression of IL12RB1 at the surface of activated T-lymphocytes and NK cells. For the moment, only one mutation of IL12 RB1 leads to residual expression of the receptor on the cell surface. Low IFN-gamma levels are measured by ELISA after whole blood activation by BCG and BCG+IL-12. Genetic testing reveals mutations in IL12RB1. Impaired development of the Th17 cells is demonstrated in patients with this immunodeficiency.
Differential diagnosis
Other genetic etiologies of MSMD should be excluded.
Antenatal diagnosis
This immunodeficiency is not severe and antenatal diagnosis is not necessary.
Genetic counseling
MSMD due to complete IL12RB1 deficiency is inherited in an autosomal recessive manner so genetic counseling is possible.
Management and treatment
BCG vaccination should be avoided in those with a known mutation in the IL12RB1 gene. Treatment is usually attained from long term antimicrobial therapy combined with recombinant IFN-gamma. For those who have localized splenic/mesenteric lesions with poor drug penetration, surgical removal is indicated.
Prognosis
With proper treatment the prognosis is usually good with most patients reaching adulthood.

                            Last update: 
                            February 2013


                            - Expert reviewer(s): 
                            Dr Jacinta BUSTAMANTE  - Pr Jean-Laurent CASANOVA
Mendelian susceptibility to mycobacterial diseases due to complete ISG15 deficiency (ORPHA:319563)
Mendelian susceptibility to mycobacterial diseases (MSMD) due to complete ISG15 deficiency is a genetic variant of MSMD (see this term) characterized by Bacille Calmette-Guérin (BCG) infections.
Epidemiology
The prevalence is unknown. In 2012, three patients were reported from two unrelated kindreds from Turkey and Iran.
Clinical description
Patients are described to have BCG infections. Patients of 12 or 15 years of age were reported to have been infected in the past with many other viruses but with no unusually severe consequences reported.
Etiology
MSMD due to complete ISG15 deficiency is caused by mutations in the ISG15 gene (1p36.33), which encodes an IFN-alpha/beta inducible, ubiquitin-like intracellular protein. These mutations impair ISG15 secretion by leukocytes, a molecule which plays an essential role as an IFN-gamma-inducing secreted molecule needed for optimal antimycobacterial immunity.
Diagnostic methods
Diagnosis is made by laboratory analysis. IFN-gamma, IL-12p40 and IL-12p70 levels can be measured by ELISA after whole blood activation by BCG, BCG+IL-12 and BCG+IFN-gamma. Similarly to patients with an IL12RB1 deficiency, patients with an ISG15 deficiency produce small amounts of IFN-gamma whereas they produce normal amounts of IL12p40 and IL12p70. Genetic testing reveals mutations in ISG15.
Differential diagnosis
Other etiologies of MSMD, especially MSMD due to complete IL12RB1 deficiency (see this term), should be excluded.
Antenatal diagnosis
This immunodeficiency is not severe and antenatal diagnosis is not necessary.
Genetic counseling
MSMD due to complete ISG15 deficiency is inherited in an autosomal recessive manner and genetic counseling is possible.
Management and treatment
BCG vaccination should be avoided in those with a known ISG15 mutation. Treatment usually involves long term antimicrobial therapy combined with recombinant IFN-gamma.
Prognosis
With proper treatment the prognosis is presumed to be good.

                            Last update: 
                            February 2013


                            - Expert reviewer(s): 
                            Dr Jacinta BUSTAMANTE  - Pr Jean-Laurent CASANOVA
Mendelian susceptibility to mycobacterial diseases due to partial IRF8 deficiency (ORPHA:319600)
Mendelian susceptibility to mycobacterial diseases (MSMD) due to partial IRF8 (interferon regulatory factor 8) deficiency is a rare genetic variant of MSMD (see this term) characterized by a selective susceptibility to relatively mild infections with bacillus Calmette-Guérin (BCG)..
Epidemiology
The prevalence is unknown. Only 2 cases in the world have been described to date.
Clinical description
The first infections occur after vaccination with BCG and before the age of 2. They are relatively mild with manifestations of fever and lymphadenopathy. No other infectious diseases have been reported.
Etiology
MSMD due to a partial IRF8 deficiency is caused by heterozygous mutations in the IRF8 gene on chromosome 16q24.1 which encodes IRF8, a protein essential for the development of dendritic cells and the differentiation of macrophages and granulocytes. Mutations in the IRF8 gene impairs IL-12 secretion by monocytes and dendritic cells.
Genetic counseling
MSMD due to a partial IRF8 deficiency is inherited in an autosomal dominant manner so genetic counseling is possible.

                            Last update: 
                            February 2013


                            - Expert reviewer(s): 
                            Dr Jacinta BUSTAMANTE  - Pr Jean-Laurent CASANOVA
Mendelian susceptibility to mycobacterial diseases due to partial STAT1 deficiency (ORPHA:319595)
Mendelian susceptibility to mycobacterial diseases (MSMD) due to partial STAT1 (signal transducer and activator of transcription 1) deficiency is a genetic variant of MSMD (see this term) characterized by a partial defect in the interferon (IFN)-gamma pathway, leading to mild mycobacterial infections.
Epidemiology
The prevalence is unknown. In 2001, two patients from unrelated kindreds were described and they suffered only mild MSMD. Since 2001, up to six other kindreds have been described to have a partial dominant STAT1 deficiency associated with MSMD.
Clinical description
First infections occur after the age of 3, most commonly with weakly virulent Mycobacterium bovis BCG and Mycobacterium avium complex or with the more virulent Mycobacterium tuberculosis. Clinical penetrance is incomplete and some patients are asymptomatic while others have very mild clinical manifestations. None of the patients identified to date developed severe viral illness.
Etiology
MSMD due to partial STAT1 deficiency is due to heterozygous mutations in the STAT1 gene on chromosome 2q32.2-q32.3 encoding the signal transducer and activator of transcription 1. Two distinct forms have been described: one affecting phosphorylation and the other impairing DNA-binding activity.
Genetic counseling
Transmission is autosomal dominant and genetic counseling is possible.

                            Last update: 
                            February 2013


                            - Expert reviewer(s): 
                            Dr Jacinta BUSTAMANTE  - Pr Jean-Laurent CASANOVA
Meningeal melanocytoma (ORPHA:252046)
A rare nervous system tumor characterized by a benign pigmented space-occupying lesion derived from leptomeningeal melanocytes. Symptoms typically show insidious onset and are related to the mass effect on adjacent tissues. Depending on the location of the tumor, they include focal neurological deficits, increased intracranial pressure, seizures, and spinal cord compression, among others. Although the tumor may behave aggressively, prognosis is good after complete surgical resection.
Meningococcal meningitis (ORPHA:33475)
Meningococcal meningitis is an acute bacterial disease caused by Neisseria meningitides that presents usually, but not always, with a rash (non blanching petechial or purpuric rash), progressively developing signs of meningitis (fever, vomiting, headache, photophobia, and neck stiffness) and later leading to confusion, delirium and drowsiness. Neck stiffness and photophobia are often absent in infants and young children who may manifest nonspecific signs such as irritability, inconsolable crying, poor feeding, and a bulging fontanel. Meningococcal meningitis may also present as part of early or late onset sepsis in neonates. The disease is potentially fatal. Surviving patients may develop neurological sequelae that include sensorineural hearing loss, seizures, spasticity, attention deficits and intellectual disability.
Menke-Hennekam syndrome (ORPHA:592574)
A rare genetic multiple congenital anomalies/dysmorphic syndrome characterized by variable intellectual disability, developmental delay, autistic behavior, short stature, and microcephaly. Additional variable manifestations include feeding problems, vision and hearing impairments, recurrent upper airway infections, and epilepsy. Reported malformations are cryptorchidism and cerebral anomalies. Dysmorphic facial features include short and upslanted palpebral fissures, ptosis, telecanthus, depressed nasal ridge, short nose, anteverted nares, short columella, and long philtrum.
Menstrual cycle-dependent periodic fever (ORPHA:498251)
A rare anomaly of puberty or/and menstrual cycle characterized by recurrent fevers (higher than 38 degrees Celsius) associated with the luteal phase of the menstrual cycle in women.
MEPAN syndrome (ORPHA:508093)
A rare genetic neurological disorder characterized by childhood-onset dystonia with distinctive MRI changes in the basal ganglia, and optic atrophy developing either immediately or within a few years after the appearance of dystonia. Additional symptoms include chorea and other movement disorders, dysarthria, or nystagmus, among others. Motor disability progresses gradually, while cognitive function is relatively spared.
Mercury poisoning (ORPHA:330021)
Mercury poisoning is caused mainly through ingestion or inhalation of any of the 3 forms of mercury, elemental, organic, and inorganic. Exposure to elemental mercury affects the pulmonary (inhalation of mercury vapors causes coughing, chills, fever, shortness of breath), dermatological (mild swelling, vesiculation, scaling, irritation, urticaria, erythema and allergic contact dermatitis accompanied by pain), and peripheral and central nervous (CNS) systems (depression, paranoia, extreme irritability, hallucinations, inability to concentrate, memory loss, hands, head, lips, tongue, jaw and eyelids tremors, weight loss, perpetually low body temperature, drowsiness, headaches, insomnia, fatigue). Exposure to inorganic mercury generally causes development of a metallic taste, local oropharyngeal pain, nausea, vomiting, bloody diarrhea, colic abdominal pain, renal dysfunction and, neurologic abnormalities; while that to organic mercury can lead to delayed neurotoxicity.
Mesial temporal lobe epilepsy with hippocampal sclerosis (ORPHA:99701)
Mesial temporal lobe epilepsy with hippocampal sclerosis is a rare epilepsy syndrome defined by seizures originating in limbic areas of the mesial temporal lobe, particularly in the hippocampus, amygdala, and in the parahippocampal gyrus and its connections, and hippocampal sclerosis, usually unilateral or assymetric. It is frequently associated with an initial precipitating event, such as febrile seizures, hypoxia, intracranial infection or head trauma, most often occurring in the first five years of life, followed by a latent period without seizures. Typical seizures consist of a characteristic aura that is frequently a rising epigastric sensation associated with emotional disturbances, illusions, and autonomic symptoms (widened pupils, palpitations), progressive impairment of consciousness, oro-alimentary automatisms (lip smacking, chewing, licking, tooth grinding), behavioral arrest, head deviation, dystonic postures, hand and verbal automatisms. Seizures are followed by postictal dysfunction. Initially, seizures are easily controlled with antiepileptic drugs, later they frequently become refractory and associated with progressive behavioral changes and memory deficits.
Mesoaxial synostotic syndactyly with phalangeal reduction (ORPHA:157801)
A rare non-syndromic syndactyly characterized by mesoaxial reduction of fingers, complete syndactyly of the 3rd and 4th fingers with synostoses of the corresponding metacarpals and associated single phalanges, malformed thumbs, and hypoplasia and clinodactyly of the 5th finger. Preaxial webbing of toes with terminal phalangeal hypoplasia of all toes has been reported in association.
Mesocardia (ORPHA:95443)
A rare, congenital non-syndromic heart malformation characterized by an atypical location of the heart in a central position in the thorax, with the apex in the midline of the thorax. Atria are usually situs solitus, whereas ventricles may be situs inversus. Various congenital heart anomalies and visceral situs inversus have also been associated.
Mesomelic dwarfism, Reinhardt-Pfeiffer type (ORPHA:2634)
A rare disorder characterized by disproportionate short stature from birth with dysplasia of the ulna and fibula.
Epidemiology
Prevalence is unknown but only a few families have been described in the literature so far.
Clinical description
Curvatures of the forearm, radial head luxation, and tibial anomalies have also been described.
Etiology
The syndrome is transmitted in an autosomal dominant manner and cases of this dysplasia have been described in families with Langer mesomelic dwarfism and Léri-Weill dyschondrosteosis (see these terms) leading to the suggestion that this dysplasia, type Reinhardt-Pfeiffer may also be associated with haploinsufficiency of the short stature homeobox (SHOX; Xp22.33 and Yp11.32) gene or anomalies of the downstream pseudoautosomal region 1 (PAR1) where SHOX enhancer elements are located.

                            Last update: 
                            October 2009


                            - Expert reviewer(s): 
                            Dr Martine LE MERRER
Mesomelic dwarfism-cleft palate-camptodactyly syndrome (ORPHA:2631)
A rare syndrome characterised by mesomelic shortening and bowing of the limbs, camptodactyly, skin dimpling and cleft palate with retrognathia and mandibular hypoplasia. It has been described in a brother and sister born to consanguineous parents. Transmission is autosomal recessive.