An update on oculocerebrocutaneous (Delleman‐Oorthuys) syndrome

• Published in: American journal of medical genetics. Part C, Seminars in medical genetics Seminars in medical genetics, 2018-12, Vol.178 (4), p.414-422
• Main Authors: Moog, Ute, Dobyns, William B.
• Format: Article
• Language: English
• Subjects: Abnormalities, Multiple; Anomalies; Appendages; Brain; Central Nervous System Cysts - pathology; cystic microphthalmia; Deactivation; Delleman‐Oorthuys syndrome; Deoxyribonucleic acid; DNA; DNA sequencing; Eye Abnormalities - pathology; Fingers - abnormalities; Fingers - pathology; Forebrain; Genetics; Genomes; giant tectum absent vermis; Hindbrain; Humans; Inactivation; Microphthalmia; OCCS; oculocerebrocutaneous syndrome; Patients; Phenotype; polymicrogyria; Skin; Skin Abnormalities - pathology
• ISSN: 1552-4868; 1552-4876
• DOI: 10.1002/ajmg.c.31667

Oculocerebrocutaneous syndrome (OCCS) is a rare disorder characterized primarily by congenital skin, eye, and brain anomalies. The most distinctive findings are hypoplastic or aplastic skin defects; pedunculated, typically hamartomatous, or nodular skin appendages; cystic microphthalmia; and a combination of forebrain anomalies and a specific mid‐hindbrain malformation. Based on a review of 40 patients with OCCS, existing clinical criteria have been revised. Because of the asymmetric and patchy distribution of features, lack of recurrence in families, male preponderance and completely skewed X‐inactivation in one female, OCCS is hypothesized to result from postzygotic mosaic variants in an X‐linked gene. Whole exome and genome sequencing on blood DNA in two patients failed to identify pathogenic variants so far. In view of the overlapping features, in particular of the brain, of OCCS and Aicardi syndrome, both may be pathogenetically related or even result from different variants in the same gene. For the elucidation of the cause of OCCS, exome or genome sequencing on multiple lesional tissues is the primary goal.