This rare multisystem condition is also known as fasciocutaneous syndrome and is usually sporadic, possibly representing new mutations. The facial features are similar to Noonan syndrome, with increasingly coarse features with age, and nasal papillomata. There is excess skin on the hands.
Developmental delay after postnatal failure to thrive and short stature are usual. There is an increased risk of cancer, possibly up to 17 %, particularly rhabdomyosarcomas, neuroblastomas, and transitional carcinomas of the bladder, and screening by 3–6-monthly abdominal ultrasound and 6–12- monthly urinary catecholamine estimations until 5 years of age and annual urinalysis thereafter recommended until 10 years of age (DeBaun 2002; Gripp et al. 2002, 2006).
The diagnosis is based on clinical findings, with confirmation of the diagnosis requiring identification of a germline heterozygous gain-of-function missense mutations in the HRAS proto-oncogene (Aoki et al. 2005; Gripp and Lin 2012). The mutation frequency is 90 %, with virtually all mutations involving exon 2 (first coding exon) of HRAS. Therefore, if the diagnosis is suspected but no HRAS mutation is found, then other differential diagnoses should be considered. Top differential diagnoses include other syndromes involving the RAS/MAPK pathway (so-called RASopathies) including type 1 neurofibromatosis, Noonan syndrome, cranio-cardio-facial syndrome, and Legius syndrome (Gripp and Lin 2012).