Miller syndrome
Other names	Mandibulfacial dysostosis with postaxial limb anomalies
This condition is inherited in anautosomal recessive manner.

Miller syndrome, also known asGenée–Wiedemann syndrome,Wildervanck–Smith syndrome orpostaxial acrofacial dysostosis, is an extremely rare genetic condition that manifests as craniofacial, limb and eye deformities. It is caused by a mutation in theDHODH gene. The incidence of the condition is not known, and little is known about itspathogenesis.

The syndrome consists of severemicrognathia,cleft lip and/orpalate, hypoplasia or aplasia of the postaxial elements of the limbs,coloboma of theeyelids andsupernumerary nipples. Additional features of the syndrome include downward-slanting palpebral fissures,malar hypoplasia, malformedears, and a broad nasal ridge. Other features include supernumeraryvertebrae and other vertebral segmentation andrib defects,heart defects (patent ductus arteriosus,ventricular septal defect andostium primum atrial septal defect),lung disease from chronicinfection, single umbilicalartery, absence of thehemidiaphragm, hypoplasia of thefemora, ossification defects of theischium andpubis, bilobedtongue, lung hypoplasia, andrenal reflux.^{[citation needed]}

The gene responsible for this disorder isDHODH^[1][2] located at chromosome 16q22. This gene encodes anenzyme – dihydroorotate dehydrogenase – catalyses theubiquinone-mediated oxidation ofdihydroorotate toorotate, the fourth enzymatic step inde novopyrimidine biosynthesis. The protein is normally located on the outer surface of the innermitochondrial membrane.^{[citation needed]}

A mutation in this gene was reported by Morgan in 1910 in the fruit flyDrosophila melanogaster. In the fly this mutation is characterized by wing anomalies, defectiveoogenesis, and malformed posterior legs.^[3] In humans Miller syndrome is due to a recessive mutation in theDHODH gene.^[1]

The differential diagnosis includesTreacher 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]}

This section is empty. You can help byadding to it.(November 2017)

This condition was first described in 1969 by Genée, who assumed the condition to be an extreme form ofTreacher 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 Milleret 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]

Genée–Wiedemann syndrome is named after two German physicians: Ekkart Genée (1936–), and his mentorHans-Rudolf Wiedemann (1915–2006).^{[citation needed]}

• Inborn errors of purine-pyrimidine metabolism
• Syndromes affecting the eye
• Syndromes with cleft lip and/or palate
• Rare syndromes

• CS1 French-language sources (fr)
• CS1 German-language sources (de)
• CS1: long volume value
• Articles with short description
• Short description is different from Wikidata
• All articles with unsourced statements
• Articles with unsourced statements from November 2020
• Articles to be expanded from November 2017
• All articles to be expanded
• Articles with empty sections from November 2017
• All articles with empty sections