Oculo-ectodermal syndrome (OES) is an extremely rare disease (< 1:1,000,000) first described in 1993 by Toriello et al. Approximately 20 cases have been described in the literature.
OES is a mosaic developmental pathology recognised by its typical oculo-cutaneous manifestations. The aetiology of OES is post-zygotic missense variants in the proto-oncogene KRAS (on chromosome 12p12.1), in the RAS/MAPK signalling pathway. In at least 7 individuals, post-zygotic variants in the proto-oncogene KRAS, in the RAS/MAPK signalling pathway, have been identified. Many of these involve codon p. Ala146. OES is thought to be a mosaic RASopathy and shares many features with other syndromes of this group (Encephalo-cranio-cutaneous lipomatosis, Linear sebaceous nevus syndrome). The variable severity of this disease is explained by the precocity of the mutational event leading to a higher mutation burden. The hallmark clinical signs are a combination of congenital scalp lesions, referred to as aplasia cutis congenita and epibulbar dermoids. Due to mosaicism, there is a large variability in the phenotypic expression of the syndrome. They are:
- Hamartomas (myxovascular hamartoma, smooth muscle hamartoma) associated with regions of alopecia,
- Long bone non-ossifying fibromas and giant cell granulomas of the jaws have repeatedly been observed and seem to be age-dependent, becoming a common manifestation from the age of 5 years,
- Growth failure,
- Skeletal abnormalities: skull abnormality, length discrepancy in long bones, short neck, facial asymmetry,
- Ocular anomalies: defects or skin tags of the upper eyelid, corneal opacity, optic nerve or retinal abnormality, microphthalmia and glaucoma,
- Urogenital defects: bladder exstrophy, epispadias,
- Arachnoid cysts in the brain,
- Cardiovascular anomalies: hypertrophic cardiomyopathy, atrial septal defect, persistent ductus arteriosus and aortic coarctation,
- Moyamoya disease,
- Neurodevelopment symptoms can include developmental delay, learning difficulties, behavioural abnormalities or epilepsy.
An increased risk of malignancy cannot be excluded, in particular for rare specific variants, but so far there is insufficient evidence for a recommendation to screen for specific tumours. Consequently, regular clinical follow-up should be recommended for an early oncologic diagnosis. So far, there is little data on disease progression, malignancy risk or RAS‐targeted therapies in OES and, for that reason, future research is required.