IMPE Abstracts

Children with syndromic growth disorders represent a significant proportion of patients referred for pediatric or genetic evaluation. The correct diagnosis has important implications for genetic counseling, treatment, and follow-up. The clinical diagnosis of these patients is challenging because there are almost 1200 genetic syndromes in which short stature is one of the cardinal features. Each of these disorders presents distinctive clinical, laboratory, and radiologic characteristics, but owing to their rarity, the diagnosis is difficult. Additionally, several disorders present genetic heterogeneity, marked clinical variability, or nonspecific features, causing an overlap among different conditions, limiting the usefulness of a candidate gene approach to genetic diagnosis. The advent of genomic techniques for genetic investigation brought the possibility of accelerating and facilitating the diagnosis of these patients. Mainly whole-exome (WES) or whole-genome sequencing (WGS), together with analysis of copy number variants (CNVs), allows to end the diagnostic odyssey in a large proportion of patients with syndromic growth disorders. Studies have shown that molecular genetic techniques confirm up to 80% of syndromic growth disorders with a clinical diagnosis. On the other hand, a genetic diagnosis can be obtained in 30 to 50% of cases of syndromic short stature without a known cause after extensive clinical evaluation. In the lecture, we will discuss clinical and genetic assessment in this heterogeneous group of children with syndromic growth disorders. The focus will be on demonstrating how WES and WGS can be implemented in evaluating these children and their impact on their follow-up and treatment.

Recommended references:

1) Clinical relevance of systematic phenotyping and exome sequencing in patients with short stature. Hauer et al. Genet Med. 2018 Jun;20(6):630-638. PMID: 29758562

2) Growth hormone therapy in children; research and practice - A review. Collett-Solberg et al. Growth Horm IGF Res. 2019 Feb;44:20-32. PMID: 30605792

3) Genetic Disorders in Prenatal Onset Syndromic Short Stature Identified by Exome Sequencing. Homma et al J Pediatr. 2019 Dec;215:192-198. PMID: 31630891

4) Recurrent Copy Number Variants Associated with Syndromic Short Stature of Unknown Cause. Homma et al. Horm Res Paediatr. 2018;89(1):13-21. PMID: 29130988

5) High frequency of genetic/epigenetic disorders in short stature children born with very low birth weight. Freire et al. Am J Med Genet A. PMID: 35792504