[Resistance to thyroid hormone syndrome with developmental disorders in two children]

Area of Science:

• Endocrinology
• Genetics
• Pediatrics

Background:

• Resistance to thyroid hormone syndrome (RTH) presents with significant clinical heterogeneity.
• RTH can be challenging to diagnose, leading to potential misdiagnosis or delayed identification.
• Thyroid dysfunction in children often requires thorough genetic investigation.

Purpose of the Study:

• To investigate the role of THRB gene mutations in pediatric cases of resistance to thyroid hormone syndrome.
• To highlight the importance of early genetic testing for THRB mutations in children with unexplained thyroid dysfunction and developmental disorders.
• To illustrate how genetic findings guide diagnosis and treatment in RTH.

Main Methods:

• Case study analysis of two pediatric patients with clinical suspicion of RTH.
• Genetic testing to identify mutations in the THRB gene.
• Clinical evaluation including thyroid hormone levels (FT3, FT4, TSH) and developmental assessment.

Main Results:

• Patient 1: diagnosed with RTH due to a de novo THRB mutation (c.1373T>C, p.Val458Ala), presenting with delayed language development.
• Patient 2: diagnosed with pituitary-type RTH due to a de novo THRB mutation (c.959G>A, p.Arg320His), exhibiting growth delay and tachycardia.
• Both cases demonstrate the link between THRB gene mutations and RTH phenotypes.

Conclusions:

• Early THRB gene testing is essential for accurate diagnosis of RTH in pediatric patients.
• Identifying specific THRB mutations facilitates tailored treatment and management strategies.
• Prompt genetic diagnosis of RTH can prevent diagnostic delays and improve patient outcomes.