TaoMedAI/RareMedData huggingface dataset:
Midline cervical cleft (ORPHA:141288)
A rare neck malformation characterized by a congenital vertical atrophic and usually erythematous skin defect of variable length, lacking adnexal elements and located along the midline of the anterior neck. It typically presents with a superior skin tag, a midline subcutaneous fibrous cord which is often longer than the overlying skin defect, and an inferior blind sinus from which mucus can be expressed. The length of the defect increases with patients' age. Likewise, the fibrous cord becomes more prominent with age, potentially leading to restriction of neck extension if the malformation is left untreated. Other possible complications include microgenia, exostosis, torticollis, or infection.
Midline interhemispheric variant of holoprosencephaly (ORPHA:93926)
Midline interhemispheric variant of holoprosencephaly (MIH) or syntelencephaly is a form of holoprosencephaly (HPE; see this term) characterized by non-separation of the posterior frontal and parietal lobes, normally-formed callosal genu and splenium, absence of the callosal body, normally-separated hypothalamus and lentiform nucleus, and frequent heterotopic gray matter.
Epidemiology
About 2% to 15% of HPE patients have MIH type.
Clinical description
Patients have rather mild dysmorphic facial features such as ocular hypotelorism, flat or narrow nasal bridge or a relatively normal facial appearance.
Etiology
MIH has mainly been reported in patients with ZIC2 (13q32) mutations.
Prognosis
Prognosis is better than in classical forms of HPE.

                            Last update: 
                            October 2011


                            - Expert reviewer(s): 
                            Pr Sandra MERCIER  - Pr Sylvie ODENT
Mietens syndrome (ORPHA:2557)
Mietens syndrome is a very rare syndrome consisting of corneal opacity, nystagmus, strabismus, flexion contracture of the elbows with dislocation of the head of the radius and abnormally short ulnae and radii.
Epidemiology
To date, only nine cases have been reported.
Clinical description
Ocular findings are striking. Dysmorphic features are not characteristic except for a small pinched nose and a depressed nasal root. Intellectual deficit and growth delay are observed in the majority of patients.
Genetic counseling
An autosomal recessive pattern of inheritance is probable.

                            Last update: 
                            July 2010
Mikati-Najjar-Sahli syndrome (ORPHA:2558)
Mikati-Najjar-Sahli syndrome is characterized by microcephaly, hypergonadotropic hypogonadism, short stature and facial dysmorphism (a narrow forehead, hypertrophy and fusion of the eyebrows, micrognathia and pinnae abnormalities).
Epidemiology
It has been described in five siblings (three males and two females) born to consanguineous parents.
Clinical description
Additional congenital anomalies present in some of the patients included cubitus valgus and genu valgum. Early tooth loss was also reported.
Genetic counseling
The mode of transmission appears to be autosomal recessive.

                            Last update: 
                            May 2009
Mild Canavan disease (ORPHA:314918)
Mild Canavan disease (CD) is a neurodegenerative disorder characterized by mild speech delay or motor development.
Epidemiology
Mild CD has been identified in only a few cases. The majority of patients with Canavan disease have the severe form (see this term). In contrast to the severe CD, most mild CD patients are not from Ashkenazi Jewish descent.
Clinical description
Mild CD usually presents in childhood with mild developmental delay or problems with speech or motor development. Head circumference is usually normal. Retinitis pigmentosa (see this term) may be present. .
Etiology
CD is caused by mutation in the ASPA gene (17p13.3), coding for the aspartoacylase enzyme. Mild CD is associated with heterozygous genotypes comprising a mild mutation and a severe one. Mild mutations include Y288C, R71H, P257R, I143T, and Y231C.
Diagnostic methods
The brain MRI usually demonstrates an increased signal intensity in the basal ganglia and the urine level of N-acetyl-L-aspartic acid (NAA) is slightly elevated. Mutation screening can be performed for molecular diagnosis.
Prognosis
Prognosis is good and children often attend normal school but may need speech therapy or a tutor. Life expectancy is normal.

                            Last update: 
                            December 2012


                            - Expert reviewer(s): 
                            Dr Kimberlee MATALON  - Dr Reuben MATALON
Mild hemophilia A (ORPHA:169808)
A mild form of hemophilia A characterized by a small deficiency of factor VIII (biological activity between 5 and 40 IU/dL) leading to abnormal bleeding as a result of minor injuries or following surgery or tooth extraction. Spontaneous hemorrhages do not occur. Patients may be also labeled as having mild hemophilia A if they have a FVIII >40 IU/dL and a DNA change in the F8 gene and one of the following: (i) a family member with the same DNA change and FVIII of <40 IU/dL, and the DNA change is found in <1% of the population; and (ii) the international databases list the DNA change as being associated with hemophilia A and <40 IU/dL FVIII. The condition may affect males and female carriers of disease-causing mutations.
Mild hemophilia B (ORPHA:169799)
A mild form of hemophilia B characterized by a small deficiency of factor IX (biological activity between 5 and 40 IU/dL) leading to abnormal bleeding as a result of minor injuries or following trauma, surgery or tooth extraction. Spontaneous hemorrhages do not occur. The condition may affect males and female carriers of disease-causing mutations.
Mild hyperphenylalaninemia (ORPHA:79651)
A rare form of phenylketonuria, an inborn error of amino acid metabolism, characterized by blood phenylalanine (Phe) concentrations of 120-600 micromol/L with or without clinical manifestations of impaired cognitive function, and behavioral and developmental disorders.
Mild phenylketonuria (ORPHA:79253)
A mild to moderate form of phenylketouria (PKU), an inborn error of amino acid metabolism, characterized by blood phenylalanine concentrations of 600-1,200 micromol/L and manifests with reduced cognitive function and behavioral and developmental disorders. Dietary phenylalanine tolerance is 400-600 mg/day.
Mild phosphoribosylpyrophosphate synthetase superactivity (ORPHA:411536)
A mild form of phosphoribosylpyrophosphate (PRPP) synthetase superactivity, an X-linked disorder of purine metabolism, characterized by adolescent or early adult-onset hyperuricemia and hyperuricosuria, leading to urolithiasis and gout.
Epidemiology
PRPP synthetase superactivity is a rare disorder with 30 families described in the literature. The mild form accounts for approximately 75% of cases. The disorder predominantly affects males.
Clinical description
Mild PRPP synthetase superactivity typically manifests in late adolescence or early adulthood, but may manifest earlier, with uric acid crystalluria and urinary stones (kidney and/or bladder), followed by the development of gouty arthritis and eventually renal failure as a result of obstructive uropathy from uric acid crystal deposition. This form is not associated with any neurodevelopmental anomalies.
Etiology
The disease is due to overactivity of PRPP synthetase 1 (PRS-I), an enzyme that catalyzes the synthesis of PRPP, a cofactor involved in the synthesis of purine and pyrimidine nucleotides. PRS-I overactivity results in overproduction of purine nucleotides and uric acid (a waste product of purine breakdown). The exact molecular mechanism leading to the mild form is not yet well understood, but it seems to be linked to increased rates of transcription of the gene PRSP1 (Xq22.3) encoding PRS-I .
Diagnostic methods
Diagnosis is based on blood and urine analysis showing hyperuricemia, hyperuricosuria, and uric acid crystalluria. Diagnosis is confirmed by a PRS enzyme assay showing increased PRS-I activity in fibroblasts, lymphoblasts, and erythrocytes.
Differential diagnosis
Differential diagnosis includes other causes urinary stones and gout.
Antenatal diagnosis
Prenatal genetic testing in male fetuses may be possible if the mutation has been previously identified in the family.
Genetic counseling
Although no genetic mutation has been identified in this mild form, the pattern of inheritance is thought to be X-linked with complete penetrance in males. Females are not typically affected, but some females may show a mild clinical presentation.
Management and treatment
Hyperuricemia and hyperuricosuria are treated with: allopurinol or febuxostat to reduce uric acid formation and thus serum urate and urinary uric acid. A high daily fluid intake is recommended; and, as needed, potassium citrate to alkalinize the urine. Dietary recommendations include emphasis on low-fat dairy and complex carbohydrate-containing foods.
Prognosis
Severe gout can lead to renal impairment, if not properly treated.

                            Last update: 
                            April 2020


                            - Expert reviewer(s): 
                            Dr Arjan DE BROUWER
Mild spondyloepiphyseal dysplasia due to COL2A1 mutation with early-onset osteoarthritis (ORPHA:93279)
Mild spondyloepiphyseal dysplasia due to COL2A1 mutation with early-onset osteoarthritis is a type 2 collagen-related bone disorder characterized by precocious, generalized osteoarthritis (with onset as early as childhood) and mild, dysplastic spinal changes (flattening of vertebrae, irregular endplates and wedge-shaped deformities) resulting in a mildly short trunk.
Miller Fisher syndrome (ORPHA:98919)
A rare acquired peripheral neuropathy characterized by acute ophthalmoplegia, ataxia, and areflexia, typically manifesting with diplopia and unsteady gait, and generalized areflexia.
Epidemiology
Annual incidence is estimated at 1/333,333.
Clinical description
Miller Fisher syndrome (MFS) is characterized by the clinical triad of acute onset of gait ataxia, areflexia, and ophthalmoplegia. Acute onset of external ophthalmoplegia is a cardinal feature of MFS. Facial and bulbar nerve palsies have also been reported.
Etiology
In the majority of cases, MFS occurs following upper respiratory tract or gastrointestinal infections. Although the exact pathological mechanism is not fully understood, MFS is associated with the presence of antiganglioside antibodies (primarily, anti-GQ1b).
Diagnostic methods
Diagnosis is based on the clinical findings, patient history, cerebrospinal fluid (CSF) analysis (revealing raised protein levels), detection of anti-GQ1b IgG antibodies (not present in all patients), brain MRI studies are usually unremarkable, and electromyography is normal.
Differential diagnosis
The clinical picture in MFS shows clinical overlap with Bickerstaff brainstem encephalitis (BBE), which is also associated with raised titers of anti-GQ1b antibodies, leading to the suggestion that BBE and MFS represent variable manifestations of the same clinical spectrum.
Management and treatment
If the severity is high (inability to walk, or complete ophthalmoplegia), management is based on immunotherapy with intravenous immunoglobulin (IVIg) or plasma exchange. In mild cases, spontaneous recovery is expected.
Prognosis
MFS is generally self-limiting and patients recover within a few months, however, cases of progression to respiratory failure have been reported in MFS patients with features of both MFS and other forms of GBS (MFS/GBS overlap syndrome).

                            Last update: 
                            November 2023


                            - Expert reviewer(s): 
                            Pr Satoshi KUWABARA
Miller-Dieker syndrome (ORPHA:531)
Miller-Dieker Syndrome (MDS) is a contiguous gene deletion syndrome of chromosome 17p13.3, characterised by classical lissencephaly (lissencephaly type 1) and distinct facial features. Additional congenital malformations can be part of the condition.
Epidemiology
MDS is undoubtedly a rare condition with a reported estimate of 1 cases per 100 000 live births, although incidence and prevalence are probably higher.
Clinical description
Children with MDS present with severe developmental delay, usually have epilepsy, and feeding problems are common. The lissencephaly represents the severe end of the spectrum with generalized agyria, or agyria and some frontal pachygyria.
Etiology
Visible and submicroscopic deletions of 17p13.3, including the LIS1 gene, are found in almost 100% of patients.
Management and treatment
Management of children with MDS is symptomatic. To avoid the complications of feeding and swallowing problems (poor nutritional state, aspiration pneumonia), nasogastric tubes and gastrostomies (a more long-term solution) can be utilised. Seizure control is important.

                            Last update: 
                            April 2005


                            - Expert reviewer(s): 
                            Pr Daniela PILZ
Mills syndrome (ORPHA:94091)
A rare, acquired motor neuron disease characterized by a slowly progressive, unilateral, ascending or descending hemiplegia, associated to unilateral or asymmetrical pyramidal signs and no sensory loss. It is a diagnosis of exclusion and controversy exists regarding whether the presence of bulbar symptoms, sphincter disturbances, fasciculations or cognitive manifestations characterize the disease.
Milroy disease (ORPHA:79452)
Milroy disease is a frequent form of primary lymphedema (see this term) characterized generally by painless, chronic lower-limb lymphedema found at birth or developing in the early neonatal period.
Minimal pigment oculocutaneous albinism type 1 (ORPHA:352734)
An extremely rare form of Oculocutaneous albinism type 1 with minimal pigment present, characterized by blond hair (white at birth), variable iris transillumination (blue irides at birth followed by minimal development of pigment during the first decade of life), visual acuity ranging from 20/80-20/200 and white skin, with or without skin nevi.
MIRAGE syndrome (ORPHA:494433)
A rare genetic disease characterized by pre- and postnatal growth restriction, developmental delay, adrenal hypoplasia, genital abnormalities (such as microphallus, hypospadias, or cryptorchidism), thrombocytopenia and/or anemia, recurrent severe invasive infections, and enteropathy with chronic diarrhea. Myelodysplastic syndrome and dysmorphic features (including downslanting palpebral fissures, low-set and posteriorly rotated ears, anteverted nares, camptodactyly, and arachnodactyly, among others) may also be observed.
Mirizzi syndrome (ORPHA:521219)
A rare biliary tract disease characterized by external compression and subsequent obstruction of an extrahepatic biliary duct by one or more gallstones in the cystic duct or the gallbladder. Patients may present with acute or chronic cholecystitis with right upper abdominal pain, nausea, and vomiting, jaundice, or cholangitis. Cholecystobiliary or -enteric fistulae can arise due to chronic inflammation and ulceration.
Mirror polydactyly-vertebral segmentation-limbs defects syndrome (ORPHA:3004)
A rare disorder characterized by mirror polydactyly, vertebral hypersegmentation and severe congenital limb deficiencies. Duodenal atresia and absent thymus were also reported. So far, it has been described in four unrelated infants identified through a congenital malformation screening program carried out in Spain. The prevalence was estimated at around 1 in 330,000. The etiology is unknown but it was suggested that the syndrome is caused by defective expression of a developmental control gene.
Mirror-image polydactyly (ORPHA:498494)
A rare non-syndromic limb malformation characterized by a hand or foot with more than five digits that has a recognizable anterior/posterior axis of symmetry, either with a hallux- or thumb-like structure or an interdigital space in the middle. The most lateral digits on each side typically resemble fifth fingers or toes. The malformation may be unilateral or bilateral and may occur in isolation or in association with other congenital anomalies.
MiT family translocation renal cell carcinoma (ORPHA:319308)
MiT family translocation renal cell carcinoma (t-RCC) is a rare subtype of renal cell carcinoma with recurrent genetic abnormalities, harboring rearrangements of the TFE3 (Xp11 t-RCC) or TFEB [t(6;11) t-RCC] genes. The t(6;11) t-RCC has distinctive histologic features of biphasic appearance with larger epitheloid and smaller eosinophilic cells. The symptoms are usually non-specific and include hematuria, flank pain, palpable abdominal mass and/or systemic symptoms of anemia, fatigue and fever.
MITF-related melanoma and renal cell carcinoma predisposition syndrome (ORPHA:293822)
MITF-related melanoma and renal cell carcinoma predisposition syndrome is an inherited cancer-predisposing syndrome due to a gain-of-function germline mutation in the MITF gene, associated with a higher incidence of amelanotic and nodular melanoma, multiple primary melanomas and increase in nevus number and size. It may also predispose to co-occurring melanoma and renal cell carcinoma and to pancreatic cancer.
Mitochondrial DNA depletion syndrome, encephalomyopathic form with methylmalonic aciduria (ORPHA:1933)
A rare mitochondrial DNA depletion syndrome characterized by neonatal or infantile onset of global developmental delay, hypotonia, failure to thrive, progressive neurologic decline, sensorineural deafness, and movement disorder. Seizures, external ophthalmoplegia, polyneuropathy, cardiomyopathy, and renal tubular dysfunction have also been reported. Brain imaging may show T2-weighted hyperintensities in the basal ganglia, and laboratory examination may reveal lactic acidosis and mild methylmalonic aciduria.
Mitochondrial DNA depletion syndrome, encephalomyopathic form with renal tubulopathy (ORPHA:255235)
A rare mitochondrial DNA depletion syndrome characterized by neonatal or infantile onset of hypotonia, failure to thrive, global developmental delay, and persistent lactic acidosis. The disease course is variable and ranges from intractable diarrhea and respiratory failure with fatal outcome in early infancy to a milder phenotype with survival into childhood. Additional reported features include sensorineural hearing loss, microcephaly, seizures, pigmentary retinopathy, and renal tubulopathy.
Mitochondrial DNA depletion syndrome, encephalomyopathic form with variable craniofacial anomalies (ORPHA:369897)
A rare mitochondrial DNA depletion syndrome characterized by congenital or early-onset lactic acidosis, hypotonia, and severe global developmental delay with feeding difficulties and failure to thrive. It is frequently associated with variable dysmorphic facial features. Additional manifestations include seizures, movement disorders, and cardiac and ophthalmologic anomalies, among others. Brain imaging may show generalized atrophy and white matter abnormalities.
Mitochondrial DNA depletion syndrome, encephalomyopathic form (ORPHA:254803)
Mitochondrial DNA depletion syndrome, encephalomyopathic form is a group of mitochondrial DNA maintenance syndrome diseases characterized by predominantly neuromuscular manifestations with typically infantile onset of hypotonia, lactic acidosis, psychomotor delay, progressive hyperkinetic-dystonic movement disorders, external ophtalmoplegia, sensosineural hearing loss, generalized seizures and variable renal tubular dysfunction. It may be associated with a broad range of other clinical features.
Mitochondrial DNA depletion syndrome, hepatocerebrorenal form (ORPHA:363534)
A rare, genetic, mitochondrial DNA depletion syndrome characterized by neonatal or early-infantile onset hepatopathy (manifesting with hepatomegaly, cholestasis, increased transaminases, coagulopathy, hypoalbuminemia, ascites, and/or liver failure), associated with renal tubulopathy and progressive neurodegenerative manifestations, which include muscular atrophy, hyporeﬂexia, ataxia, sensory neuropathy, epilepsy, sensorineural hearing impairment, psychomotor regression, athetosis, nystagmus, and/or ophthalmoplegia. Patients typically present with recurrent vomiting, severe failure to thrive, feeding difficulties, and fasting hypoglycemia.
Mitochondrial DNA depletion syndrome, myopathic form (ORPHA:254875)
A rare mitochondrial DNA depletion syndrome characterized by muscle weakness, and progressive, generalized hypotonia due to depletion of mtDNA in skeletal muscles. Clinical progression ranges from rapid and early fatal course due to respiratory failure, to slowly progressive myopathy over the course of childhood or even early adulthood.
Mitochondrial DNA depletion syndrome (ORPHA:35698)
A clinically heterogeneous group of mitochondrial disorders characterized by a reduction of the mitochondrial DNA copy number in affected tissues without mutations or rearrangements in the mitochondrial DNA. It is phenotypically heterogeneous, and can affect a specific organ or a combination of organs, with the main presentations described being either hepatocerebral (i.e. hepatic dysfunction, psychomotor delay), myopathic (i.e. hypotonia, muscle weakness, bulbar weakness), encephalomyopathic (i.e. hypotonia, muscle weakness, psychomotor delay) or neurogastrointestinal (i.e gastrointestinal dysmotility, peripheral neuropathy). Additional phenotypes include fatal infantile lactic acidosis with methylmalonic aciduria, spastic ataxia (early-onset spastic ataxia-neuropathy syndrome), and Alpers syndrome.
Mitochondrial DNA-associated Leigh syndrome (ORPHA:255210)
Maternally inherited Leigh syndrome is a rare subtype of Leigh syndrome (see this term) characterized clinically by encephalopathy, lactic acidosis, seizures, cardiomyopathy, respiratory disorders and developmental delay, with onset in infancy or early childhood, and resulting from maternally-inherited mutations in mitochondrial DNA.
Mitochondrial DNA-related cardiomyopathy and hearing loss (ORPHA:1349)
A rare mitochondrial disease that has a heterogeneous clinical presentation characterized by the association of progressive sensorineural hearing loss with hypertrophic cardiomyopathy and, in the majority of cases, encephalomyopathy symptoms such as ataxia, slurred speech, progressive external opthalmoparesis (PEO), muscle weakness, myalgia, and exercise intolerance.
Mitochondrial DNA-related dystonia (ORPHA:254851)
Maternally-inherited mitochondrial dystonia is a rare neurological mitochondrial DNA-related disorder characterized clinically by progressive pediatric-onset dystonia with variable degrees of severity.
Mitochondrial DNA-related mitochondrial myopathy (ORPHA:254788)
A group of rare mitochondrial oxidative phosphorylation disorders due to mitochondrial DNA anomalies characterized by progressive, most commonly proximal, myopathy with variable degrees of weakness, exercise-induced muscle pain, and fatigue. Progressive external ophthalmoplegia is often observed. Additional features include neurological signs and symptoms (such as seizures, stroke-like episodes, or developmental delay), cardiomyopathy, involvement of liver, kidneys, and gastrointestinal tract, and diabetes. Lactic acidosis is frequently present, while recurrent rhabdomyolysis and myoglobinuria are rare. Muscle biopsy may reveal the presence of ragged-red fibers and a mosaic pattern of cytochrome c oxidase-negative fibers.
Mitochondrial hypertrophic cardiomyopathy with lactic acidosis due to MTO1 deficiency (ORPHA:314637)
A rare mitochondrial oxidative phosphorylation disorder with complex I and IV deficiency characterized by lactic acidosis, hypotonia, hypertrophic cardiomyopathy and global developmental delay. Other clinical features include feeding difficulties, failure to thrive, seizures, optic atrophy and ataxia.