Noonan-like Syndrome with Loose Anagen Hair Due to SHOC2 Mutation: A Case Report

1. Junior Resident, Department of Paediatrics, PGIMS Rohtak, Haryana, India. 2. Junior Resident, Department of Paediatrics, PGIMS Rohtak, Haryana, India. 3. Junior Resident, Department of Paediatrics, PGIMS Rohtak, Haryana, India. 4. Junior Resident, Department of Paediatrics, PGIMS Rohtak, Haryana, India. 5. Junior Resident, Department of Paediatrics, PGIMS Rohtak, Haryana, India.

Abstract

Noonan syndrome is an autosomal dominant genetic condition, although some cases arise from de novo mutations, which has an approximate prevalence of 1:1000 to 1:2500 live births with many underlying gene mutations in RAS/MAPK pathways whereby common gene mutations being PTPN11 and SOS1. However, some rare pathogenic gene mutation like SHOC2 may be seen leading to phenotypical Noonan syndrome. The authors report novel clinical features in the index case, described as Noonan-like Syndrome with Loose Anagen Hair (NS/LAH). Authors, hereby, report a 12-year-old male who presented with global developmental delay, speech impairment, short stature, characteristic dysmorphic features, left-sided hemiparesis, and skin findings including ichthyosis and atopic dermatitis. Whole exome sequencing identified a pathogenic SHOC2 mutation consistent with the diagnosis of NS/LAH. Uniquely, a concurrent pathogenic BRCA1 variant was identified, though the child exhibited no signs of malignancy at presentation. This case expands the known clinical spectrum of SHOC2-related RASopathies by presenting an unusual association with unilateral motor deficits and a novel co-occurrence with a BRCA1 mutation. While SHOC2 mutations are known to disrupt RAS/MAPK pathway signalling, their relationship with motor asymmetry and overlapping cancer-risk gene variants like BRCA1 is not well-established. We emphasise the importance of comprehensive genetic evaluation in children with atypical phenotypes and unexplained developmental delays. Early recognition and long-term surveillance are critical in such complex genetic cases to identify evolving features and associated risks.

Autosomal dominant inheritance, Cell signalling pathway, Developmental delay, Pathogenic gene mutation