Atypical case of Rett syndrome with concurrent MECP2 gene mutation and del(15)(q22qter) karyotype: A case report and review of literature

Abstract

BACKGROUND

Rett syndrome is a monogenic X-linked dominant condition that affects 1/(10000-15000) girls due to de novo mutations in the methyl-CpG binding protein 2 (MECP2) gene mapped to chromosome Xq28. The disease-causing gene was identified as a mutation in the MECP2 gene, which is found in approximately 80% of patients diagnosed with Rett syndrome. Although chromosomal changes resulting in del(15)(q11q13) are usually associated with Angelman and Prader-Willi syndrome, very few cases, if any, of Rett syndrome with terminal 15q22-qter deletion have been published in English literature.

CASE SUMMARY

In this study, we report an unusual and rare clinical presentation of Rett syndrome in a 12-year-old Sudanese girl. The patient was brought in by her parents, complaining of gradual onset of abnormal walking, abnormal hand movement, loss of speech, and mental retardation for ten years. There was no reported history of convulsions or loss of consciousness. Clinical examination revealed microcephaly with no other apparent dysmorphic features, intact cranial nerves, and abnormal gait. She showed repetitive and stereotyped behaviors, including hand flapping, stimming, and chest pounding, which were concomitant with autism spectrum disorder. Magnetic resonance imaging and electroencephalography investigations were normal, and cytogenetic analysis showed 46,XX, del(15)(q22qter). Further molecular analysis using whole sequencing of MECP2 revealed an alteration cytosine > thymine at nucleotide 401, leading to phenylalanine replacing a serine at amino acid position 134.

CONCLUSION

This case, the first reported instance of Rett syndrome in Sudan, is of significant interest. The patient carries both the MECP2 gene mutation and the chromosome 15q22-qter deletion, which may explain the autistic behavior with atypical presentation of Rett syndrome. This report expands the genetic diversity of Rett syndrome, demonstrating how co-occurring 15q22-qter deletions can reshape MECP2-associated phenotypes in Rett syndrome.

Keywords: Rett syndrome; Autism spectrum disorder; Methyl-CpG-binding protein two gene mutation, Chromosome 15 deletion; Atypical presentation; Chromosomal analysis; Case report

Core Tip: This report presents a rare atypical case of Rett syndrome with a novel concomitant of a pathogenic methyl-CpG binding protein 2 p.S134F mutation and 15q22-qter karyotype from Sudan. The patient displayed atypical Rett syndrome phenotype, including significant growth regression and pronounced autistic behaviors, stereotypic hand-flapping and chest-pounding, and absence seizures. The terminal 15q22-qter deletion may disrupt critical neurodevelopmental loci (such as ubiquitin-protein ligase E3A and insulin-like growth factor 1 receptor), which could exacerbate autism and growth failure while potentially reducing susceptibility to seizures. This case expands the phenotypic and genotypic heterogeneity of Rett syndrome, enhances our understanding of how synchronous genomic alterations modulate methyl-CpG binding protein 2-related phenotypes, and underscores the imperative for equitable genetic diagnostics in underrepresented populations.