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Keywords: Chromosomal deletions; Intellectual and developmental disability; Dysmorphology; Copy number/structural variation; Chromosomal structure/function

S. Upadhya 1; G. Verdi 1; J.L. Smith 2; S.H. Elsea 2; B. Nelson 4, 5; K. Yearwood 5; H. Hakonarson 3; D. Li 3; E.J. Bhoj 3; A.K. Sobering 1

1) Department of Biochemistry, St. George's University School of Medicine, Grenada; 2) Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA; 3) Center for Applied Genomics, Children’s Hospital of Philadelphia, Philadelphia, PA, USA; 4) Grenada General Hospital, Pediatrics Ward, Grenada; 5) Clinical Teaching Unit, St. George’s University School of Medicine, Grenada

The experience for families of children born with developmental delay in low- and middle-income nations is in stark contrast to high-income nations. In resource-limited countries, barriers to obtaining genetic diagnosis might involve economic disparities, geographical isolation, and inadequate access to genetic medicine. As part of a combined teaching, research, and community outreach effort, we provided genetic testing for a child with global developmental delay (GDD), dysmorphology, and intellectual disability (ID). Deletions involving the terminal region of 18q may lead to a variable phenotype including short stature, developmental delay (DD), hypotonia, hearing impairment and foot deformities (OMIM 601808). Duplications of the 5p terminal region cause DD, ID, and variable facial dysmorphology (OMIM 613174).
We present a 5-year-old Afro-Caribbean boy who has GDD, ID, hypotonia, feeding difficulties, facial dysmorphology and bilateral club feet. Speech development is limited to less than 5 words. He can walk for a short distance with an unstable gait. He has a high frontal hairline with a prominent widow’s peak, frontal bossing, a flat and broad nasal bridge, up-slanting palpebral fissures, hypertelorism, and camptodactyly. His feet are internally rotated, and the right foot is worse than the left. Both of his parents are healthy. The family described a now deceased maternal aunt who they thought had Down syndrome, but to our knowledge, she was never medically evaluated. He has two maternal aunts who have primary infertility. Conventional karyotyping showed additional chromatin of unknown origin on the long arm of chromosome 18. Cytogenomic microarray analysis showed a 6.4 Mb deletion (chr18:71518518-77943115) on chromosome 18 and a 24 Mb duplication (chr5:8097721-32062984) of material from chromosome 5. We postulate that the combined clinical features of our patient are due to deletions of regions of chromosome 18 and the partial duplication of chromosome 5. We are now in the process of offering a karyotype to both parents. A definitive diagnosis is beneficial to these families and can assist in providing answers with reassurance, and allows for informed genetic counseling and recurrence risk assessment, especially if a balanced translocation is found in a parent as suspected.