Familial Case of Morris Syndrome: Clinical Observations

Hormonal regulation plays a crucial role in human sexual development. Mutations in the androgen receptor gene may cause peripheral androgen resistance, leading to characteristic phenotypic manifestations. In complete androgen resistance, patients develop a female phenotype despite disrupted sexual differentiation, which is mediated by aromatization of testosterone into estrogen. One of the typical complaints reported by patients is the presence of a groin bulge, often bilateral, which is perceived as an inguinal hernia. Surgical treatment in the form of gonadectomy may result in impaired bone mineral metabolism or masculinization; on the other hand, delayed intervention increases the risk of malignancy. This article presents a familial case of Morris syndrome with a previously undescribed AR gene mutation (NM_001011645.3) in two girls aged 14 and 6 years. Both girls were admitted for elective repair of bilateral inguinal hernias observed since birth. During hernioplasty, testes were discovered and biopsied, revealing testicular tissue in the first case and tunica albuginea in the second. Based on intraoperative findings, further evaluation was performed, including ultrasound of the genitourinary system, hormonal testing, medical genetic testing, and consultations with endocrinologist and geneticist. In both cases, androgen insensitivity syndrome was confirmed (a hemizygous AR gene variant was identified in exon 7: HG38, chrX:67721856T> C, c.746T> C, resulting in the amino acid substitution p.Met249Thr). DNA sequencing revealed the AR gene mutation in the mother in a heterozygous state. No pathogenic variants were identified in the father, older sister, or brother. With parental consent, both patients underwent bilateral laparoscopic gonadectomy. The study highlights the importance of age, including in relation to sexual and phenotypic development, when determining the timing of surgical intervention. It also underscores the need for a comprehensive, multidisciplinary approach to address functional, social, and gender-related issues in these patients.