Oculocerebrocutaneous syndrome (ORPHA:1647)
A rare neurologic disease typically characterized by the triad of eye, central nervous system and skin malformations, and often associated with an intellectual disability.
Epidemiology
Prevalence is unknown, but around 40 cases have been reported to date. Oculocerebrocutaneous syndrome (OCCS) is predominantly found in males.
Clinical description
Neonates, predominantly boys, typically present with an orbital cyst or cystic microphthalmia, often in combination with eyelid colobomata. Cutaneous features often include striated muscle hamartoma, multiple cutaneous tags in the periorbital region (pedunculated/finger-like), and focal aplasia/hypoplasia (mainly on the neck, face and scalp). Developmental delay and intellectual disability may vary from very mild to profound. About half of the patients have a history of epileptic seizures, however they are well controlled in most cases. OCCS has a wide spectrum of clinical symptoms beyond the typical clinical triad, with skull, rib and vertebral anomalies, craniofacial clefts including a defect of the nasal ala in some cases, and abnormal ear pinnae. Cryptorchidism is occasionally reported.
Etiology
Etiology remains elusive. OCCS is hypothesized to be a postzygotic mosaic condition.
Diagnostic methods
Diagnosis is based on the presence of the triad of eye, central nervous system (CNS) and cutaneous clinical features. It is confirmed on magnetic resonance imaging (MRI) by the demonstration of : 1) mainly asymmetrical forebrain malformations with polymicrogyria (PMG), periventricular nodular heterotopias located beneath the PMG, interhemispheric or intraventricular cysts, enlarged ventricles or hydrocephalus, and partial or complete agenesis of the corpus callosum; and 2) provisionally unique mid-hindbrain malformations, characterized by giant tectum, absent or severely malformed vermis and posterior fossa malformation with cerebellar hypoplasia and widening of the fourth ventricular outflow tract. Electroencephalogram (EEG) is abnormal in 50% of cases.
Differential diagnosis
Differential diagnosis includes encephalocraniocutaneous lipomatosis, but the multitude of mesenchymal tumors (in particular lipomas, and choristomas) and CNS anomalies exclude it from OCCS. The brain malformations overlap substantially with those seen in Aicardi syndrome although the mid-hindbrain malformation is unkown in Aicardi syndrome and the typical chorioretinal lacunae associated with Aicardi syndrome are unknown in OCCS. Goldenhar syndrome, focal dermal hypoplasia and microphthalmia with linear skin defects should also be considered. The mid-hindbrain malformations may be confused with Dandy-Walker malformation, but are often complex and severe in OCCS.
Genetic counseling
OCCS occurs sporadically. The preponderance of males suggests that OCCS may be an X-linked disorder.
Management and treatment
Management should involve a multidisciplinary team composed of an ophthalmologist, neurologist and pediatrician. Removal of the orbital cyst may be done by aspiration and dissection from the adjacent periocular region. Sclerosing therapy with ethanolamine oleate may be used. Because of the cerebral or cerebellar malformations and consequent manifestations, a neurological evaluation is necessary before deciding on a surgical intervention.
Prognosis
OCCS has been fatal in 15% of the reported cases. Most surviving patients have significant psychomotor deficiencies but a normal development has been reported in at least 15% of the cases.

                            Last update: 
                            August 2019


                            - Expert reviewer(s): 
                            Pr Ute MOOG