Delleman-Oorthuys or oculocerebrocutaneous syndrome (OCCS) is an extremely rare condition which relies on three pillars of manifestations: ophthalmological, neurological, and dermatological. It was first described by Delleman and Oorthuys in 1981, and since then, very few other cases have been reported. We report the case of a 13-month-old boy, referred to an ophthalmological tertiary service for investigation of a microglobe with a cystic retrobulbar mass on translucency test. MRI revealed a left microphthalmia, with extensive retrobulbar cystic lesions occupying the remaining orbit and protruding anteriorly the microglobe. Cerebral findings included polymicrogyria, subependymal nodular heterotopia at the level of the left occipital horn of the lateral ventricle, and an importantly enlarged mesencephalic tectum observed in association with an absent cerebellar vermis. The ensemble of malformations met the criteria for definite OCCS. Being a tremendously rare syndrome, OCCS will always represent a diagnostic challenge. However, its emblematic cutaneous manifestations might be an important part of the road map leading to its correct interpretation. Thus, when absent, diagnosis can be harder than usual, and, on these cases, neurologists, ophthalmologists, and radiologists play a crucial role.

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.