Proteus syndrome is characterized by progressive segmental or patchy overgrowth most commonly affecting the skeleton, skin, adipose, and central nervous systems. In most individuals Proteus syndrome has modest or no manifestations at birth, develops and progresses rapidly beginning in the toddler period, and relentlessly progresses through childhood, causing severe overgrowth and disfigurement. It is associated with a range of tumors, pulmonary complications, and a striking predisposition to deep vein thrombosis and pulmonary embolism.

A rare congenital malformation syndrome, most commonly presenting with hemifacial microsomia associated with ear and/or eye malformations and vertebral anomalies of variable severity. Additional malformations involving the heart, kidneys, central nervous, digestive and skeletal systems may also be associated. The phenotypic spectrum ranges from isolated mild facial asymmetry to severe bilateral craniofacial microsomia and additional multiple extracranial abnormalities. Intelligence is typically normal. The aetiology is poorly understood but is suspected to be heterogeneous and multifactorial. The gene MYT1 (20q13.33) has been implicated in a few rare cases, and chromosomal abnormalities have been associated with some of the congenital malformations associated with this condition. The condition usually occurs sporadically, but autosomal dominant inheritance has been reported.

Encephalocraniocutaneous lipomatosis (ECCL) comprises a spectrum of predominantly congenital anomalies. In its typical form, ECCL is characterized by congenital anomalies of the skin (nevus psiloliparus, patchy or streaky non-scarring alopecia, subcutaneous lipomas in the frontotemporal region, focal skin aplasia or hypoplasia on the scalp, and/or small nodular skin tags on the eyelids or between the outer canthus and tragus), eye (choristoma), and brain (in particular intracranial and spinal lipomas). To a much lesser degree, the bones and the heart can be affected. About 40% of affected individuals have bilateral abnormalities of the skin or the eyes. About one third of affected individuals have normal cognitive development, another one third have mild developmental delay (DD) or intellectual disability (ID), and the final one third have severe or unspecified DD/ID. Half of individuals have seizures. Affected individuals are at an increased (i.e., above the general population) risk of developing brain tumors, particularly low-grade gliomas such as pilocytic astrocytomas. There is evidence that oculoectodermal syndrome (OES) may constitute a clinical spectrum with ECCL, with OES on the mild end and ECCL on the more severe end of the spectrum.

Oculoectodermal syndrome (OES) is characterized by the association of epibulbar dermoids and aplasia cutis congenita. Affected individuals exhibit congenital scalp lesions which are atrophic, nonscarring, hairless regions that are often multiple and asymmetric in distribution, and may have associated hamartomas. Ectodermal changes include linear hyperpigmentation that may follow the lines of Blaschko and, rarely, epidermal nevus-like lesions. Epibulbar dermoids may be uni- or bilateral. Additional ocular anomalies such as skin tags of the upper eyelid and rarely optic nerve or retinal changes or microphthalmia can be present. Phenotypic expression is highly variable, and various other abnormalities have occasionally been reported, including growth failure, lymphedema, and cardiovascular defects, as well as neurodevelopmental symptoms such as developmental delay, epilepsy, learning difficulties, and behavioral abnormalities. Benign tumor-like lesions such as nonossifying fibromas of the long bones and giant cell granulomas of the jaws have repeatedly been observed and appear to be age-dependent, becoming a common manifestation in individuals aged 5 years or older (summary by Boppudi et al., 2016).