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. 2011 Sep;1(6):282-289.
doi: 10.1159/000331266. Epub 2011 Sep 14.

RASopathies: Clinical Diagnosis in the First Year of Life

M C Digilio  1 , F Lepri, A Baban, M L Dentici, P Versacci, R Capolino, R Ferese, A De Luca, M Tartaglia, B Marino, B Dallapiccola
Affiliations

RASopathies: Clinical Diagnosis in the First Year of Life

M C Digilio et al. Mol Syndromol. 2011 Sep.

Abstract

Diagnosis within Noonan syndrome and related disorders (RASopathies) still presents a challenge during the first months of life, since most clinical features used to differentiate these conditions become manifest later in childhood. Here, we retrospectively reviewed the clinical records referred to the first year of life of 57 subjects with molecularly confirmed diagnosis of RASopathy, to define the early clinical features characterizing these disorders and improve our knowledge on natural history. Mildly or markedly expressed facial features were invariably present. Congenital heart defects were the clinical issue leading to medical attention in patients with Noonan syndrome and LEOPARD syndrome. Feeding difficulties and developmental motor delay represented the most recurrent features occurring in subjects with cardiofaciocutaneous syndrome and Costello syndrome. Thin hair was prevalent among SHOC2 and BRAF mutation-positive infants. Café-au-lait spots were found in patients with LS and PTPN11 mutations, while keratosis pilaris was more common in individuals with SOS1, SHOC2 and BRAF mutations. In conclusion, some characteristics can be used as hints for suspecting a RASopathy during the first months of life, and individual RASopathies may be suspected by analysis of specific clinical signs. In the first year of life, these include congenital heart defects, severity of feeding difficulties and delay of developmental milestones, hair and skin anomalies, which may help to distinguish different entities, for their subsequent molecular confirmation and appropriate clinical management.

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Figures

Fig. 1
Fig. 1
Faces of infants with RASopathies. The panels show representative facial features occurring in newborns and infants with Noonan syndrome caused by PTPN11, RAF1, SOS1 and NRAS mutations (a–d), LEOPARD syndrome due to a PTPN11 mutation (e), Noonan-like syndrome with loose anagen hair resulting from the c.A>G change in SHOC2 (f), cardiofaciocutaneous syndrome due to BRAF (g) and MEK2 (h) mutations, and Costello syndrome caused by the c.34G>A HRAS mutation (i).
See this image and copyright information in PMC

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