Oculocerebrocutaneous Syndrome

Delleman and Oorthuys (1981) reported 2 presumably unrelated boys with orbital cyst, cerebral malformations, and focal dermal hypo- and aplasia. Despite some similarities to the Goltz (305600) and Goldenhar (164210) syndromes, a new entity was suspected. In neither case were the parents related. 'Punched out' lesions over the nasal alae and in other areas were found in both. In one case the maternal grandmother had unilateral congenital clinical anophthalmia. Moog et al. (1996) presented the long-term follow-up of a 19-year-old patient who was one of the first 2 patients described by Delleman and Oorthuys (1981).

Delleman et al. (1984) added 2 new cases. Al-Gazali et al. (1988) reviewed 5 published cases and reported 4 new cases. They illustrated a dramatic example of unilateral orbital cyst as well as examples of periorbital skin appendages. All cases have been sporadic. Giorgi et al. (1989) described another case. Also see Wilson et al. (1985). Hoo et al. (1991) reported a case in which, as in most cases, involvement was mainly unilateral. Among reported cases, left involvement has dominated over right involvement by about 2 to 1.

Moog et al. (1996) reported a new case of this disorder presenting with bilateral clinical anophthalmia and orbital cysts, typical skin lesions, a complex brain malformation, and cleft lip/palate. The infant died due to the severe cerebral malformations at the age of 10 months. Moog et al. (1996) considered the most important differential diagnostic entities to be encephalocraniocutaneous lipomatosis, focal dermal hypoplasia (FDH; 305600), and microphthalmia with linear skin defects (MCOPS7; 309801). Moog et al. (1997) reported 3 new cases and reviewed the clinical features of 23 previously reported cases. The 3 new cases were sporadic. They all had cystic microphthalmia, abnormalities of the ventricular system, and lipomatous skin tags. In addition, 2 of the 3 had Dandy-Walker malformation and focal dermal hypoplastic defects. The 2 children who survived the neonatal period had psychomotor retardation and epilepsy. Twenty-four of the 26 patients reviewed had a colobomatous ocular defect, and all 26 had at least 1 ocular feature. Twenty-four patients had skin appendages, and in 21 of these the appendages were mainly around the orbit. Twenty-one had focal dermal hypoplasia or aplasia. A great variety of cerebral malformations was seen, with 3 patients having a normal CT scan. Of the 17 patients greater than 6 months of age at the time of report, all showed psychomotor retardation, and 13 showed seizures or an abnormal EEG. Moog et al. (1997) concluded that the triad of ocular, cutaneous, and cerebral features were characteristic of the syndrome and that, in particular, the ocular features were typical and constant. They also noted the difficulty in differentiating oculocerebrocutaneous syndrome from encephalocraniocutaneous lipomatosis. Moog et al. (1997) reported that the most reliable discriminating features were orbital cysts and agenesis of the corpus callosum, which are unknown in encephalocraniocutaneous lipomatosis, and cerebral calcifications, which are unreported in oculocerebrocutaneous syndrome.

Moog et al. (1997) reported an 18-to-7 preponderance of male infants. Family history was negative in all but 1 of the patients reported by Delleman and Oorthuys (1981) and in 1 of the cases reported by Al-Gazali et al. (1988), where a paternal cousin had an eye cyst and the mother of the proband had a bilateral coloboma.

Happle (1987) suggested that oculocerebrocutaneous syndrome, like a number of other sporadically occurring disorders with an irregular distribution of skin involvement, may be the result of an autosomal dominant lethal gene that is compatible with survival only in the mosaic state. Moog et al. (1997) argued that a dominant lethal mutation with survival only in mosaic form (Happle, 1987) was an unlikely etiologic mechanism because there was little variation in the tissues involved and because the skin lesions were distributed in a known linear pattern without sharp midline delineation. Moog et al. (1997) suggested that the pathogenic mechanism is probably disruption of the anterior neuroectodermal plate leading to neurocristopathy with primary craniofacial dysmorphogenesis.

Leichtman et al. (1994) and Angle and Hersh (1997) described children with what was suggested to be a more severe form of OCCS who also had anophthalmia, congenital hydrocephalus, and cleft lip and palate. McCandless and Robin (1998) described a third case of severe OCCS in an infant girl with a similar constellation of findings and additional anomalies including lateral facial cleft, vertebral anomaly, and ventricular septal defect. The additional findings pointed to phenotypic overlap of OCCS and the Goldenhar anomaly (164210), an overlap previously noted by Delleman and Oorthuys (1981) and Al-Gazali et al. (1988). McCandless and Robin (1998) suggested that the minimal diagnostic criteria for Delleman syndrome includes central nervous system cyst or hydrocephalus, orbital cysts or microphthalmia, and focal skin defects.

Moog et al. (2005) reviewed brain imaging studies, clinical records, photographs, and pathology specimens of 2 new and 9 previously reported patients with OCCS. They found a consistent pattern of malformations in 8 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 consisting of an enlarged, dysplastic tectum, absent cerebellar vermis, small cerebellar hemispheres, and a large posterior fossa fluid collection. The 3 remaining patients had similar but less severe forebrain abnormalities and lacked the mid-hindbrain malformation. Moog et al. (2005) suggested that the mid-hindbrain malformation is pathognomonic for OCCS and may be used to distinguish OCCS from related syndromes with comparable forebrain anomalies.

Nomenclature

See 309800 for discussion of the misuse of the term 'anophthalmia' in the medical literature.