Aljaafreh Suliman, Alhwayan Ayman, Altawarh Atwa, Altarawneh Moath, Alhazaimeh Ruba, Abdalnabi Abeer, Alquraan Eman, Alabdallat Sleman, Alrababah Sumaia, Khader Maher
Pediatric Department, Royal Medical Services, Queen Rania Children's Hospital, Amman, JOR.
Cureus. 2025 Jul 28;17(7):e88943. doi: 10.7759/cureus.88943. eCollection 2025 Jul.
Alpha-thalassemia X-linked intellectual disability syndrome (ATR-X syndrome) is a rare genetic disorder caused by mutations in the 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 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.
X连锁α地中海贫血智力障碍综合征（ATR-X综合征）是一种由基因突变引起的罕见遗传病，通常影响男性，表现为神经发育和全身症状。据我们所知，我们报告了约旦首例经基因确诊的ATR-X综合征病例，该病例为一名两岁半男性患者，表现为全面发育迟缓、面容畸形、肌张力低下和双侧多囊肾。尽管存在持续性小细胞贫血，但血红蛋白电泳和α珠蛋白基因缺失的PCR检测均为阴性。全外显子测序（WES）在该基因中鉴定出一个半合子致病变异：c.7365C>T（p.Arg2465Cys），从而确诊。该病例强调了某些突变可能不存在α地中海贫血，有助于全球对ATR-X综合征的理解。值得注意的是，进行性肾脏异常的存在拓宽了已知的表型谱。我们的研究结果强调了基因组诊断的重要性，特别是在资源有限的环境中，对于罕见综合征表现的准确识别和早期干预。
