Abstract
Noonan syndrome (NS) diagnosis may be challenging because of diverse clinical manifestations. This case report highlights a novel role for MAP3K7 in NS. A 10.4-year-old female patient presented with short stature and clinical findings suggestive of RASopathy. Despite atypical facial features, the patient met two major van der Burgt diagnostic criteria. Initial genetic testing for known NS-associated genes did not find any variants. Later, whole exome sequencing identified a unique de novo heterozygous variant [c.65C>A, p.(P22H)] in MAP3K7. This variant, categorized as a variant of uncertain significance by the American College of Medical Genetics and Genomics criteria, raised questions about its potential role in NS. The patient’s clinical presentation deviated from classical manifestations of MAP3K7-associated syndromes, highlighting the complexity of MAP3K7 genetic and molecular mechanisms. Notably, this is the first case reported to associate MAP3K7 variants with NS. Despite the known challenges in NS diagnosis, proper management, including recombinant growth hormone therapy, is important to optimize growth potential. The case suggests that MAP3K7 may be a potential candidate gene for NS, but more functional genetic investigations are required to clarify the delicate interaction between genetic abnormalities, the RAS/mitogen-activated protein kinase pathway, and clinical manifestations observed in NS cases.
Keywords: Noonan syndrome, short stature, MAP3K7
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