Medicine:Miller syndrome
| Miller syndrome | |
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| Other names | Mandibulfacial dysostosis with postaxial limb anomalies |
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| This condition is inherited in an autosomal recessive manner. | |
Miller syndrome, also known as Genée–Wiedemann syndrome, Wildervanck–Smith syndrome or postaxial acrofacial dysostosis, is an extremely rare genetic condition that manifests as craniofacial, limb and eye deformities. It is caused by a mutation in the DHODH gene. The incidence of the condition is not known, and nothing is known about its pathogenesis.
Presentation
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 and ostium primum atrial septal 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.[citation needed]
Cause
The gene responsible for this disorder is DHODH[1][2] located at chromosome 16q22. This gene encodes an enzyme – dihydroorotate dehydrogenase – 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.[citation needed]
Genetics
A mutation in this gene was reported by Morgan in 1910 in the fruit fly Drosophila melanogaster. In the fly this mutation is characterized by wing anomalies, defective oogenesis, and malformed posterior legs.[3] In humans Miller syndrome is due to a recessive mutation in the DHODH gene.[1]
Diagnosis
Differential diagnosis
The differential diagnosis includes Treacher Collins syndrome, Nager acrofacial dysostosis (preaxial cranial dysostosis). Other types of axial cranial dysostosis included the Kelly, Reynolds, Arens (Tel Aviv), Rodríguez (Madrid), Richieri-Costa and Patterson-Stevenson-Fontaine forms.[citation needed]
Treatment
History
This condition was first described in 1969 by Genée, who assumed the condition to be an extreme form of Treacher Collins syndrome (dysostosis mandibulofacialis).[4] Wiedemann in 1975 described it as a separate entity.[5] Further cases were reported by Wildervanck in 1975[6] and by Miller et al in 1979[7] The syndrome was named the Genée-Wiedemann syndrome in 1987.[8] A family harboring Miller syndrome was the first human family to be ever sequenced with whole genome sequencing.[9]
Eponym
Genée–Wiedemann syndrome is named after two German physicians: Ekkart Genée (1936–), and his mentor Hans-Rudolf Wiedemann (1915–2006).[citation needed]
References
- ↑ 1.0 1.1 "Exome sequencing identifies the cause of a mendelian disorder". Nature Genetics 42 (1): 30–5. January 2010. doi:10.1038/ng.499. PMID 19915526.
- ↑ "Analysis of genetic inheritance in a family quartet by whole-genome sequencing". Science 328 (5978): 636–9. April 2010. doi:10.1126/science.1186802. PMID 20220176. Bibcode: 2010Sci...328..636R.
- ↑ "Sex limited inheritance in drosophila". Science 32 (812): 120–2. July 1910. doi:10.1126/science.32.812.120. PMID 17759620. Bibcode: 1910Sci....32..120M. https://zenodo.org/record/1448044.
- ↑ "Une forme de dysostose mandibulo-faciale" (in French). J. De Génét. Humaine 17: 45–52. 1969.
- ↑ "Missbildungs-Retardierungs-Syndrom mit Fehlen des 5. Strahls an Händen und Füssen, Gaumenspalte, dysplastischen Ohren und Augenlidern und radioulnarer Synostose" (in German). Klin Padiatr 185 (3): 181–6. 1973. PMID 4795571.
- ↑ "Case report 28.". Syndrome Identification 3 (1): 1–13. 1975.
- ↑ "Postaxial acrofacial dysostosis syndrome". The Journal of Pediatrics 95 (6): 970–5. December 1979. doi:10.1016/S0022-3476(79)80285-1. PMID 501501.
- ↑ "The Genée-Wiedemann syndrome, an acrofacial dysostosis--further observation". American Journal of Medical Genetics 27 (4): 971–5. August 1987. doi:10.1002/ajmg.1320270427. PMID 3425606.
- ↑ McAuliffe, Kathleen (April 27, 2011). "#5: Family Genomics Links DNA to Disease". Discover January/February 2011. https://www.discovermagazine.com/planet-earth/5-family-genomics-links-dna-to-disease.
External links
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