Coexistence of Rare Genetic Disorders in a Consanguineous Family: Case Study of KLHL24-Related Hypertrophic Cardiomyopathy and Char Syndrome

Author(s)

Linnenkamp, Bianca Domit Werner ; Pires, Lucas Vieira Lacerda ; Stephan, Bruno de Oliveira ; Vilalva, Kelvin Henrique ; de Carvalho, Mariana Lombardi Peres ; Lipari, Layara Fernanda Vicente Pereira ; Fernandes, Fabio ; Krieger, Jose Eduardo

• Document type: Journal article
• Source: MOLECULAR SYNDROMOLOGY; v. N/A, p. 7-pg., 2024-09-17.

Abstract

Introduction: Physicians often search for a single underlying cause that explains all of a patient's signs and symptoms. However, evidence from the literature suggests that the concurrent presence of two rare diseases, although uncommon, poses significant diagnostic challenges. Precision medicine is increasingly important in these scenarios, enabling more rapid diagnosis and tailored treatments. Case Presentation: This report discusses a patient involving a consanguineous Brazilian family, where two sisters are diagnosed with autosomal recessive KLHL24-related hypertrophic cardiomyopathy. Additionally, one sister is diagnosed with Char syndrome due to a TFAP2B deletion. Conclusion: This case underscores the possibility that multiple rare genetic disorders can coexist, contributing to complex clinical phenotypes. Whole-exome sequencing proves to be a critical tool in identifying the genetic underpinnings of such complex cases, facilitating precise diagnosis and genetic counseling. The discovery of a homozygous KLHL24 variant further broadens the known mutation spectrum and underscores its significance in autosomal recessive hypertrophic cardiomyopathy. (AU)

• FAPESP's process: 13/17368-0 - Cardiovascular genomics: mechanisms & novel therapeutics - CVGen mech2ther
• Grantee: José Eduardo Krieger
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 15/50216-5 - Characterization of the optimal hiPSC-derived cardiac cell population for heart regeneration after myocardial infarction
• Grantee: José Eduardo Krieger
• Support Opportunities: Research Grants - Research Partnership for Technological Innovation - PITE
• FAPESP's process: 14/50889-7 - National Institute of Science and Technology Medicine Assisted by Scientific Computing (INCT-MACC)
• Grantee: José Eduardo Krieger
• Support Opportunities: Research Projects - Thematic Grants