Pitfalls in Genetic Testing for Consanguineous Pediatric Populations

Maha Saleh; Samantha Colaiacovo; Melanie P Napier; Asuri N Prasad; C Anthony Rupar; Chitra Prasad

doi:10.1155/2022/9393042

Pitfalls in Genetic Testing for Consanguineous Pediatric Populations

Case Rep Genet. 2022 May 25:2022:9393042. doi: 10.1155/2022/9393042. eCollection 2022.

Authors

Maha Saleh^{1

2}, Samantha Colaiacovo¹, Melanie P Napier¹, Asuri N Prasad^{2

3}, C Anthony Rupar^{1

2

4}, Chitra Prasad^{1

2}

Affiliations

¹ Division of Genetics and Metabolics, Department of Pediatrics, London Health Sciences, London, Ontario, Canada.
² Western University, London, Ontario, Canada.
³ Division of Neurology, Department of Pediatrics, London Health Sciences, London, Ontario, Canada.
⁴ Department of Pathology and Laboratory Medicine, London Health Sciences, London, Ontario, Canada.

Abstract

We describe the diagnostic odyssey of an eight-year-old female born to consanguineous parents. Our patient presented with global developmental delay, regression, microcephaly, spastic diplegia, and leukodystrophy confirmed on brain magnetic resonance imaging (MRI). She was found on whole exome sequencing (WES) to have dual genetic diagnoses. The first was a homozygous pathogenic HERC2 gene partial deletion of exons 43-45 that causes HERC2-related disorder. The second was a homozygous pathogenic variant (c.836 C > T, p.A279 V) in the SUMF1 gene responsible for multiple sulfatase deficiency. This case highlights some of the challenges in diagnosing consanguineous pediatric populations where standard genetic and metabolic testing may not provide answers. Our case further supports the recent American College of Medical Genetics and Genomics (ACMG) recommendation of WES as a first or second-tier test for patients with developmental delay, particularly in a population where the chances of dual diagnosis is high.

Publication types

Case Reports