Clinical and genetic analysis of a female child with duplications at 7p22.3p22.1 and Xp22.31p21.1: A case report.

Abstract

Rationale: Intellectual disability (ID) is a neurodevelopmental disorder with diverse etiologies. Chromosomal duplications are recognized as a common cause of ID, with manifestations typically milder than those associated with deletions. Duplications involving the short arm of chromosome 7 or the X chromosome have been linked to ID. Limited data exist on duplications at 7p22.1p22.3 and Xp22.31p21.1, leaving their clinical significance largely unexplored. This case report aims to expand the phenotype and genetics spectrum of 7p22 duplication syndrome and X-linked ID. Special attention should be paid to closely monitoring the pubertal progression of such patients.

Patient concerns: A 9-year-10-month-old female was admitted to our hospital due to distinctive dysmorphic features and ID.

Diagnoses: Upon examination, features of craniofacial dysmorphism were observed, including micrognathia, a prominent lower lip, a thin upper lip, a flat nasal bridge, and hypertelorism. The child's pubertal development is progressing extremely rapidly; at under 10 years old, the breasts have already advanced to Tanner Stage 4. Her height was within the median range, but her bone age was advanced (12.1 years). Her full-scale intelligence quotient, assessed using the Wechsler Intelligence Scale for Children: 4th edition, was 41.

Interventions: Whole exome sequencing identified a de novo duplication spanning overlapping regions at Xp21-22 and 7p22. This duplication encompasses several genes implicated in ID, including Duchenne muscular dystrophy, Aristaless-related homeobox, interleukin-1 receptor accessory protein like 1, adaptor-related protein complex 1 subunit sigma 2, and cyclin-dependent kinase-like 5.

Outcomes: A novel duplication in the Xp and 7p of a Chinese female child diagnosed with ID and dysmorphic features has been studied by whole exome sequencing analysis. The novel duplications were a large duplication located in the 7p22.1 to p22.3 region, spanning 12.07 Mb, and a large duplication located in the Xp22.31 to p21.1 region, spanning 24.7 Mb.

Lessons: Our study underscores the importance of comprehensive clinical and genetic evaluation in individuals with duplication on the X chromosome and the terminal region of chromosome 7's short arm. We highlight the need for monitoring these patients for growth and sexual development issues. Our findings also suggest that chromosomal duplication can lead to severe clinical manifestations, emphasizing the critical role of genetic assessment in managing such cases.