Same Phenotype in Children with Growth Hormone Deficiency and Resistance

Area of Science:

• Pediatric Endocrinology
• Genetics
• Metabolic Disorders

Background:

• Short stature affects approximately 2.5% of children, with idiopathic GH deficiency (IGHD) and GH insensitivity (GHI) presenting similar phenotypes despite distinct underlying mechanisms.
• Both IGHD and GHI are characterized by low serum IGF-I levels, complicating differential diagnosis based solely on clinical presentation.

Observation:

• Two pediatric cases with short stature and overlapping phenotypes were investigated.
• Case 1: Exhibited frontal bossing, doll face, acromicria, truncal obesity, minimal GH response, and undetectable IGF-I, diagnosed as IGHD type IA.
• Case 2: Presented with cranium hypoplasia, large head, saddle nose, underdeveloped mandible, micropenis, high basal GH, and persistently low IGF-I, diagnosed as Laron syndrome (GHI).

Findings:

• Idiopathic GH deficiency type IA and Laron syndrome demonstrate opposite circulating GH levels (low vs. high) but share reduced IGF-I levels.
• Both conditions result in a lack of IGF-I effects on cartilage, contributing to the similar clinical phenotypes observed in affected children.

Implications:

• Accurate differential diagnosis is essential for managing children with severe short stature, particularly distinguishing between IGHD and GHI.
• Molecular analysis of GH1 and GHR genes is critical for confirming diagnoses and understanding the specific molecular defects.
• Understanding these distinct conditions aids in developing targeted therapeutic strategies for growth disorders.