Cerebrooculonasal Syndrome

Clinical Features

Richieri-Costa and Guion-Almeida (1993) reported 2 unrelated girls with an MCA/MR syndrome of clinical anophthalmia, abnormal nares, central nervous system anomalies, and mental retardation. They referred to the condition as cerebrooculonasal syndrome. Guion-Almeida et al. (2000) reported 2 additional cases, one with and one without structural anomalies of the central nervous system and clinical anophthalmia, and both with abnormal nares. The first case reported by Guion-Almeida et al. (2000) was a female with brachycephaly, a large forehead with a depression in the midline, ocular hypertelorism, telecanthus, epicanthic folds, downslanting palpebral fissures, medial abnormally placed eyebrows, and sparse eyelashes. The nose was abnormally modeled with a proboscis-like appearance and, on the right, a small and atypical appendage-like structure. She also had malar hypoplasia, a large philtrum, a high-arched and narrow palate, and posteriorly rotated ears with a hypoplastic tragus and large conchae. Development was very mildly delayed. The second case was a male with normal growth but macrobrachycephaly, a large forehead with midline capillary hemangioma, flat supraorbital ridges, ocular hypertelorism, epicanthic folds, downslanting palpebral fissures, sparse and medially absent eyebrows, sparse eyelashes, and bilateral clinical anophthalmia. The nose was abnormally shaped and proboscis-like with marked hypoplasia of the left nostril. He also had malar hypoplasia, an atypical cleft lip, a high-arched palate, bilateral pedunculated postaxial polydactyly, genital hypoplasia, and delayed neuropsychologic development. At age 2 years he was unable to walk alone and spoke few words. Both patients showed a single maxillary central incisor.

Guion-Almeida et al. (2007) reported on 13 new patients with cerebrooculonasal syndrome and reviewed 7 previously described cases. The female to male sex ratio was 12:8. All cases occurred sporadically, and no consanguinity was present. No chromosomal abnormalities were found. The authors found marked clinical variability among the patients, but noted that the nasal configuration appeared to be unique and diagnostic. They identified a mutation, a V908G change in the PTCH gene (601309.0015), in only 1 of their patients (patient 7). Ribeiro et al. (2006) had identified the same mutation in the same patient, whom they had diagnosed with holoprosencephaly-7 (HPE7; 610828).

Kokitsu-Nakata et al. (2009) described the cerebrooculonasal syndrome in the first child of nonconsanguineous parents. He had brachycephaly, wide forehead, bilateral frontal encephalocele, malar hypoplasia, hypertelorism, bilateral anophthalmia, bilateral proboscis-like nares, cleft lip, abnormal palate, abnormal left auricular lobule, and cryptorchidism.

Inheritance

Guion-Almeida et al. (2000) suggested autosomal dominant inheritance for cerebrooculonasal syndrome because all reported cases have been sporadic and there is some evidence for advanced paternal age effect.

Nomenclature

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