Gonadal Failure in a Male With 3-M Syndrome

Area of Science:

• Genetics and Endocrinology
• Rare Genetic Disorders

Background:

• 3-M syndrome (OMIM 273750) is a rare genetic disorder characterized by severe short stature and dysmorphic features, often linked to pathogenic variants in genes like CUL7.
• While short stature is a primary feature, associated anomalies like hypogonadism and hypospadias are infrequently reported in males.

Observation:

• This report details a male patient with a CUL7 pathogenic variant presenting with congenital anomalies including bifid scrotum and perineal hypospadias.
• The patient experienced spontaneous pubertal development but later showed regression of testicular volumes and altered hormone levels.

Findings:

• The patient exhibited delayed pubertal progression with decreased testicular volume and elevated gonadotropins, despite testosterone levels remaining within the lower normal range.
• This clinical course suggests a potential for pubertal dysfunction in males with CUL7-related 3-M syndrome.

Implications:

• This case emphasizes the critical importance of ongoing pubertal monitoring in individuals diagnosed with 3-M syndrome.
• Early identification and management of pubertal disturbances are essential for comprehensive patient care in this rare genetic condition.