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Oculocerebrocutaneous syndrome: the brain malformation defines a core phenotype
  1. U Moog1,
  2. M C Jones2,
  3. L M Bird2,
  4. W B Dobyns3
  1. 1Department of Clinical Genetics, University Hospital Maastricht, Maastricht University, Maastricht, Netherlands
  2. 2Department of Dysmorphology and Genetics, Children’s Hospital San Diego, San Diego, California, USA
  3. 3Departments of Human Genetics, Neurology and Pediatrics, The University of Chicago, Chicago, Illinois, USA
  1. Correspondence to:
 Dr Ute Moog
 Department of Clinical Genetics, University Hospital Maastricht, PO Box 5800, 6202 AZ Maastricht, Netherlands; ute.moog{at}


Background: Oculocerebrocutaneous syndrome (OCCS) is characterised by orbital cysts and anophthalmia or microphthalmia, focal aplastic or hypoplastic skin defects, skin appendages, and brain malformations. The eye and skin abnormalities are well described but the neuropathological features less so. To date, 28 patients with an unequivocal diagnosis of OCCS have been reported, with a preponderance of males.

Objective: To evaluate the brain imaging studies, clinical records, photographs, and pathological material of two new and nine previously reported cases of OCCS.

Results: There was a consistent pattern of malformations in eight of the 11 cases, consisting of frontal predominant polymicrogyria and periventricular nodular heterotopia, enlarged lateral ventricles or hydrocephalus, agenesis of the corpus callosum sometimes associated with interhemispheric cysts, and a novel mid-hindbrain malformation. The latter consisted of a giant and dysplastic tectum, absent cerebellar vermis, small cerebellar hemispheres in most cases, and a large posterior fossa fluid collection.

Conclusions: The mid-hindbrain malformation appears pathognomonic for OCCS. The eye and skin features of OCCS show considerable overlap with several other syndromes, such as encephalocraniocutaneous lipomatosis, oculo-auriculo-vertebral spectrum, and focal dermal hypoplasia, none of which has a comparable pattern of brain malformations. In particular the unique mid-hindbrain malformation also distinguishes OCCS from related syndromes with comparable forebrain anomalies. The pattern of malformation described thus helps in differentiating OCCS from other entities. The mid-hindbrain malformation points to a defect of the mid-hindbrain organiser as the underlying pathogenic mechanism.

  • DWM, Dandy–Walker malformation
  • ECCL, encephalocraniocutaneous lipomatosis
  • FDH, focal dermal hypoplasia
  • OAVS, oculoauriculovertebral spectrum
  • OCCS, oculocerebrocutaneous syndrome
  • PEG, pneumoencephalography
  • PMG, polymicrogyria
  • PNH, periventricular nodular heterotopia
  • oculocerebrocutaneous syndrome
  • polymicrogyria
  • giant tectum
  • absent vermis

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  • Competing interests: none declared

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