46,XY disorders of sex development and muscular dystrophy caused by Xp21 duplication: a case report and literature review.

Background: The development of the testes is a tightly regulated process, requiring the coordination of multiple genes. Mutations in these genes can result in 46,XY gonadal dysgenesis. NR0B1, located at Xp21, is a gene expressed in the developing adrenals, gonads, hypothalamus, and pituitary gland. Duplication of this area causes dosage sensitive male-to-female sex reversal and involves multisystem abnormalities. The heterogeneity in clinical phenotypes is attributed to variations in the size of the duplicated segments. Herein, we present a case with 46,XY disorders of sex development and muscular dystrophy due to Xp21 duplication.

Case description: A 5-month-old boy was admitted to our hospital due to gonadal dysgenesis. The patient was born to a healthy couple after 37+4 weeks of pregnancy and with a natural delivery. In the course of the disease, the child showed marked growth retardation, elevated muscle enzymes and liver enzymes. During the follow-up, he developed hypotonia and low muscle strength. Chromosomal microarray analysis (CMA) testing uncovered a 7.79 Mb duplication at Xp21 in both the patient and his mother, encompassing 30 coding genes, including the NR0B1 and DMD genes.

Conclusions: The duplication of Xp21 can result in a rare genetic disorder characterized by various abnormalities in males, including short stature, mental retardation, muscular dystrophy, and gonadal dysplasia. These symptoms are often overlooked and misdiagnosed. Targeted gene detection should be completed to enable early diagnosis and intervention to improve prognosis. This study has enhanced clinicians' understanding of the disease.