Chromosome 3q27 Deletion

Correa Brito et al. “46,XY DSD with Partial Gonadal Dysgenesis and Growth Failure in a Patient with 3q27.1 Microdeletion: Candidate Gene Curation After Exhaustive Literature Review”. “International Journal of Molecular Sciences” 2025, v. 27, 821

Disorders of sex development (DSDs) refer to a group of congenital conditions in which there is a discordance between chromosomal, gonadal, and/or genital sex. In 46,XY gonadal dysgenesis, a subtype of DSD, an individual has a normal 46,XY karyotype, but their internal and/or external sex organs do not appear typically male. Correa Brito et al. present a now 11-year-old male Argentinian patient, whose birth history was marked by low birth weight and external genitalia with reduced masculinization (or moderate undervirilization). Imaging revealed a very small, underdeveloped uterus two small gonads (sex glands) located in the folds of skin near the external genitals, and a pouch or canal that resembled a vagina. Subsequent karyotype revealed chromosomes typical of males—46, XY. He was continually followed for his DSD and eventually had hypospadias correction. As he grew, he was noted to have global developmental delay, learning difficulties, and short stature. The patient also had strabismus and dysmorphic features such as low-set ears, retrognathia, flat forehead, highly arched eyebrows, long eyelashes, upslanted palpebral fissures, broad nasal tip, smooth philtrum, and a prominent nasal bridge. Due to the growth delays, the patient was then put on growth hormone therapy. Later, whole exome sequencing reanalysis revealed a pathogenic 2.7 Mb microdeletion at 3q27.1q27.2. Small for gestational age and short stature are observed features in 3q27.1 microdeletion syndrome. However, to the authors knowledge, gonadal dysgenesis has not been described as a typical phenotype. The authors then performed a literature review of 3q27.1 deletions and identified five cases with signs compatible with mild gonadal dysgenesis. The authors suggest AP2M1, DVL3, and PARL as candidate genes for prenatal and postnatal growth restriction features, while also suggesting DVL3 and CLCN2 as candidate genes for the genital anomalies. Ultimately, the authors suggest that a DSD may be an underrepresented medical concern of 3q27.1 microdeletion syndrome, though more research is necessary to corroborate these findings.

Chromosome Disorder Outreach Inc. medical geneticist and medical advisor Dr. Iosif Lurie M.D. Ph.D examines newly published research studies to locate the most important and relevant for our members. Synopses of these articles are then posted to our website’s research pages. Review and formatting by Nicole Talaba, MS CGC. For more information on any article please contact info@chromodisorder.org