A Genetically Confirmed Case of ATR-X Syndrome Without Alpha-Thalassemia: First Case Reported From Jordan

Abstract

Alpha-thalassemia X-linked intellectual disability syndrome (ATR-X syndrome) is a rare genetic disorder caused by mutations in the ATRX gene, typically affecting males and presenting with neurodevelopmental and systemic manifestations. We report, to the best of our knowledge, the first genetically confirmed case of ATR-X syndrome in Jordan, involving a two-and-a-half-year-old male patient who presented with global developmental delay, dysmorphic facies, hypotonia, and bilateral cystic kidneys. Despite persistent microcytic anemia, hemoglobin electrophoresis and PCR for alpha-globin gene deletions were negative. Whole-exome sequencing (WES) identified a hemizygous pathogenic variant in the ATRX gene: c.7365C>T (p.Arg2465Cys), confirming the diagnosis. This case contributes to the global understanding of ATR-X syndrome by emphasizing that alpha-thalassemia may be absent in certain mutations. Notably, the presence of progressive renal abnormalities broadens the known phenotypic spectrum. Our findings underscore the importance of genomic diagnostics, especially in resource-limited settings, for accurate identification and early intervention in rare syndromic presentations.

Keywords: alpha-thalassemia; atr-x syndrome; chromatin remodeling disorders; intellectual disability; whole-exome sequencing.