Mild phenotype in two siblings with a missense GHR variant

Area of Science:

• Genetics
• Endocrinology
• Pediatrics

Background:

• Laron syndrome (LS) results from growth hormone receptor (GHR) defects, leading to severe growth retardation.
• Classical LS phenotype includes distinct facial features and profound short stature.

Observation:

• A case report details two siblings, a sister and brother, diagnosed with LS.
• They presented with a homozygous c.344A>C (p.Asn115Thr) variant in the GHR gene.
• Their clinical presentation exhibited milder dysmorphism and higher height SDS than typical LS.

Findings:

• The identified GHR variant (c.344A>C) has been reported in three other LS cases.
• These siblings showed distinct clinical and biochemical characteristics compared to previously reported cases with the same variant.
• Variable expressivity of the GHR variant was observed between the siblings.

Implications:

• This case highlights the phenotypic variability associated with specific GHR gene variants.
• Understanding variable expressivity is crucial for accurate LS diagnosis and genetic counseling.
• Further research into modifier genes may explain differing phenotypes in LS.