A familial case of interstitial deletion of the short arm of chromosome 6p22.3-p24.3 in twins with severe delay in psychomotor and speech development.

Abstract

Interstitial deletions of the short arm of chromosome 6 are even rarer than distal deletions of 6p24-pter, with an incidence rate of 1:1,000,000 (according to MalaCards, https://www.malacards.org/). These deletions are associated with developmental delays, autism spectrum disorders, congenital anomalies, and dysmorphic features. The objective of our study was to identify chromosomal abnormalities in twins from a Yakut family exhibiting severe psycho-speech developmental delays, intellectual disability combined with dysmorphisms, and congenital anomalies. In this paper, two new cases involving monozygotic twins from a Yakut family, who underwent array comparative genomic hybridization (aCGH), were reported. The diagnostic results revealed a rare interstitial deletion in the region 6p22.3-p24.3, measuring 7.5 Mb, which was subsequently confirmed using a conventional cytogenetics (GTG-banding) method. According to the cytogenetic analysis, the karyotypes of the parents were normal, indicating a de novo structural chromosomal rearrangement in the patients. Additionally, a comparative phenotypic analysis of these twins with each other and with other previously reported patients was performed; they were found to have overlapping deletions in the 6p22-p24 region. Furthermore, a literature review and an analysis of the gene content of the deleted region 6p22.3-p24.3 were conducted, and so was a discussion of the genotype-phenotype correlation. The results of the phenotypic analysis revealed both common and distinct dysmorphogenic features, including craniofacial dysmorphisms, deformities of the auricles, and abnormalities in the development of the upper and lower limbs, which are often mentioned in the literature. However, the analyzed data, both from the literature and our observations, showed that all patients lacked a common deleted region in the 6p22-p24 area, creating challenges in establishing an accurate diagnosis. The findings indicate the complexity of defining the minimally overlapping region responsible for the observed phenotypic and behavioral traits and highlight the importance of a systematic and multi-level approach to diagnosing severe psycho-speech developmental delays.