- Miller syndrome
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Miller syndrome Classification and external resources OMIM #263750 This condition is also known as the Genee-Wiedemann syndrome, Wildervanck-Smith syndrome or postaxial acrofacial dystosis (POADS). The incidence of this condition is not known but it is considered extremely rare. Nothing is presently known of its pathogenesis.
Contents
History
This condition was first described by in 1969 by Genée who assumed the condition to be an extreme form of dysostosis mandibulofacialis[1] Wiedemann in 1975 described it as a separate entity.[2] Further cases were reported by Wildervanck in 1975 [3]and by Miller et al in 1979 [4] The syndrome was named the Genée-Wiedemann syndrome in 1987[5]
Genomics
The gene responsible for this disorder is DHODH[6][7] located at chromosome 16q22. This gene encodes an enzyme - dihydroorotate dehydrogenase - which catalyses the ubiquinone-mediated oxidation of dihydroorotate to orotate, the fourth enzymatic step in de novo pyrimidine biosynthesis. The protein is normally located on the outer surface of the inner mitochondrial membrane.
Genetics
A mutation in this gene was reported by Morgan in 1910 in the fruit fly Drosophila melanogaster. In the fly this mutations is characterized by wing anomalies, defective oogenesis, as well as malformed posterior legs.[8]
Clinical
The syndrome consists of severe micrognathia, cleft lip and/or palate, hypoplasia or aplasia of the postaxial elements of the limbs, coloboma of the eyelids and supernumerary nipples. Additional features of the syndrome include downward slanting palpebral fissures, malar hypoplasia, malformed ears and a broad nasal ridge. Other features include supernumerary vertebrae and other vertebral segmentation and rib defects, heart defects (patent ductus arteriosus, ventricular septal defect, ossium primum and endocardial cushion defect), lung disease from chronic infection, single umbilical artery, absence of the hemidiaphragm, hypoplasia of the femora, ossification defects of the ischium and pubis, bilobed tongue, lung hypoplasia and renal reflux.
The differential diagnosis includes Treacher Collins syndrome, Nager acrofacial dysostosis (pre axial cranial dysostosis). Other types of axial cranial dysostosis included the Kelly, Reynolds, Arens (Tel Aviv), Rodríguez (Madrid), Richieri-Costa and Patterson-Stevenson-Fontaine forms.
References
- ^ Genée E. (1969) Une forme de dysostose mandibulo-faciale. J. de génét. humaine 17: 45-52
- ^ Wiedemann H.-R. (1973) Missbildungs-Retardierungs-Syndrom mit Fehlen des 5. Strahls an Händen und Füssen, Gaumenspalte, dysplastische Ohren und Augenlidern und radioulnarer Synostose. Klinische Pädiatrie 185: 181-186
- ^ Wildervanck LS (1975) Case report 28. Syndrome Identification 3(1): 1-13
- ^ Miller M, Fineman R, Smith DW (1979) Postaxial acrofacial dysostosis syndrome. J. Pediat. 95: 970-975
- ^ Opitz JM, Stickler GB (1987) The Genée-Wiedemann syndrome, an acrofacial dysostosis – further observations. Am. J. Med. Genet 971-975
- ^ Ng SB, Buckingham KJ, Lee C, Bigham AW, Tabor HK, Dent KM, Huff CD, Shannon PT, Jabs EW, Nickerson DA, Shendure J, Bamshad MJ.(2010) Exome sequencing identifies the cause of a mendelian disorder. Nat Genet. 42(1):30-35
- ^ Biesecker L.G. (2010) Exome sequencing makes medical genomics a reality. Genet. 42(1):13-14
- ^ 0. Morgan, T. H. (1910) Sex limited inheritance in Drosophila. Science 32: 120-122
Inborn error of purine-pyrimidine metabolism (E79, 277.2) Purine metabolism AnabolismCatabolismPyrimidine metabolism AnabolismOrotic aciduria · Miller syndromeCatabolismCategories:
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