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Postaxial acrofacial dysostosis
A rare acrofacial dysostosis that is characterized by mandibular and malar hypoplasia, small and cup-shaped ears, lower lid ectropion, and symmetrical postaxial limb deficiencies with absence of the fifth digital rays and ulnar hypoplasia.
ORPHA:246Classification level: Disorder
- Acrofacial dysostosis, Genee-Wiedemann type
- Mandibulofacial dysostosis with postaxial limb anomalies
- Miller syndrome
- Postaxial acrodysostosis
- Prevalence: <1 / 1 000 000
- Inheritance: Autosomal recessive
- Age of onset: Neonatal, Antenatal
- ICD-10: Q75.4
- OMIM: 263750
- UMLS: C0265257
- MeSH: -
- GARD: 8410
- MedDRA: -
Less than 30 cases of Postaxial acrofacial dysostosis (POADS) have been described in the literature.
Clinical features further include cholestasis, bilateral inguinal hernia and cleft palate. The patients can develop myopic astigmatism and speech delay can be present. Facial features include sparse eyebrows, almond shaped eyes with up-slanting palpebral fissures, malar hypoplasia, long philtrum, small mouth, and low-set, malformed ears.
The disease arises from biallelic gene mutations for the enzyme dihydroorotate dehydrogenase (DHODH, 16q22.2), involved in pyrimidine biosynthesis. Nonetheless, despite demonstrated loss of enzyme activity, dihydroorotate (DHO) has not been shown to accumulate.
DHODH mutations can be determined by PCR and Sanger sequencing. Analysis of DHO and orotic acid (OA) in urine, plasma and blood-spot test can be performed using liquid chromatography-tandem mass spectrometry.
The clinical phenotype of Miller syndrome overlaps with mandibulofacial and other acrofacial dysostosis syndromes including Treacher Collins, Guion-Almeida (mandibulofacial dysostosis with microcephaly) and Nager syndromes.
Due to postaxial oligodactyly of fingers and toes, the diagnosis can be established prenatally on clinical grounds and confirmed by molecular testing.
Inheritance appears to be autosomal recessive. For parents of an affected individual, there is a 25% risk of having and affected child at each pregnancy. Recurrence risk for children of an affected individual is low if there is no consanguinity.
Management and treatment
The patients do not usually need surgical treatment, but sometimes need hearing aids. Logopedic treatment might be helpful.
There is usually no reduced life expectancy, but intrauterine death has been described.
A summary on this disease is available in Deutsch (2007) Italiano (2007) Español (2020) Français (2020) Nederlands (2020) Polski (2007, pdf)