Clinical Heterogeneity in two patients with Noonan-like Syndrome associated with the same SHOC2 mutation

Donatella Capalbo,Giorgia Minopoli,Claudio Pignata,Mariacarolina Salerno,Maria Giuseppa Scala,Daniela Melis,Loredana Palamaro,Nicola Improda

doi:10.1186/1824-7288-38-48

Donatella Capalbo, Giorgia Minopoli + Show 6 more

Open Access

https://doi.org/10.1186/1824-7288-38-48

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Abstract

Noonan-like syndrome with loose anagen hair (NS/LAH; OMIM #607721) has been recently related to the invariant c.4A > G missense change in SHOC2. It is characterized by features reminiscent of Noonan syndrome. Ectodermal involvement, short stature associated to growth hormone (GH) deficiency (GHD), and cognitive deficits are common features. We compare in two patients with molecularly confirmed NS/LAH diagnosis, the clinical phenotype and pathogenetic mechanism underlying short stature. In particular, while both the patients exhibited a severe short stature, GH/IGFI axis functional evaluation revealed a different pathogenetic alteration, suggesting in one patient an upstream alteration (typical GHD) and in the other one a peripheral GH insensitivity.Since only a few cases of NS/LAH associated to SHOC2 mutations have been so far described, the complex phenotype of the syndrome and the exact mechanism impairing GH/IGFI axis still remain to be elucidated and studies on larger cohort of subjects are needed to better delineate this syndrome.

Highlights

Noonan-like syndrome with loose anagen hair (NS/LAH; OMIM #607721) has been recently related to the invariant c.4A > G missense change in SHOC2
Short stature is one of the most common features observed in NS as well as in other disorders associated to RAS-MAPK dysregulation
The most common form of GH insensitivity (GHI) is due to GHR mutations; other forms are caused by abnormalities in the signaling cascade downstream to GHR and, in particular, involving STAT5b [9,11]

Summary

Short stature

Lymphatic dysplasias of LH 14.4 mU/mL; peak of FSH 21.7 mU/mL). No pubertal progression was observed in the following years and at the age of 16 years she was started on hormonal replacement. The complex clinical phenotype prompted to the clinical diagnosis of NS/LAH and molecular analysis of SHOC2 revealed the presence of the disease-causing mutation (c.4A > G, p.Ser2Gly).

Discussion

Conclusion