Endocrine Abstracts

JOINT2952

Introduction: MAMLD1(Mastermind like domain containing1, )on the Xq28 found specific expression in fetal sertoli and leydig cells. It was identified as critical for the development of male genitalia and predicted to enhance the expression of several Leydig cell-specific genes via Hes3-related Notch signaling pathway. Its hemizygous pathogenic variants cause 46, XY differences/disorders of sex development (DSD), hypomasculinized external genitalia at birth and are possibly associated with age-dependent deterioration of testicular function. It may play an important role in the testicular function including testosterone production during the fetal period and after birth.

Case: Here we describe a patient (46, XY) manifested penoscrotal hypospadias with micropenis and bilateral cryptorchidism. The male proband is the first child of his healthy, nonconsanguineous parents. He was born at 30 wk, with a weight of 2, 800 g (3, 8SD) and a length of 42. 0 cm(0, 57 SD). Cryptorchidism, penoscrotal hypospadias with micropenis, bifid scrotum was detected and he had bilateral orchiopexy at 6 months of age. A stimulation test with hCG (10 months) showed significant increase in testosterone concentrations(stimulated testesteron 302ng/dl, stimulated DHT 18ng/dl, stimulated androstenodion 6ng/dl) at 10 months of age, stimulated T/DHT ratio was >12 initially lead to the suspicion of 5α-reductase deficiency. However, mutation analysis of the SRD5A2 and AR gene was not detected. Bilateral testiculer microlithiaisis was detected at ten years old. Calcific density showed significant increased in US throughout the follow-up period. At the age of 14, according to the Tanner, right and left testis volumes were 12 and 15 cc, LH, FSH and total testesteron, AMH values were 11, 4mU/mL, 12, 5 mU/mL, 560 ng/dl, 4, 54 ng/ml respectively. Serum β-hCG and AFPlevels were within normal limits. Because of risk factor for testicular tumor, our patient underwent whole exome sequencing with CNV, MAMLD1 gene deletion on exon 3-5 was identified. Surgical right testis biopsy was applied, multifocal germ cell neoplasia in situ was detected. The focal immature seminiferous tubules with leyding cell hyperplasia were observed.

Discussion: Patients with 46, XYDSD harbouring MAMLD1variants manifest a broad spectrum of phenotypes and mostly present with hypospadias. Although both testes were descended into the scrotum within the first year of life and Sertoli/leydig cells produced sufficient hormones during pubertyin our patient, a testicular tumor developed. This is the first reported Mamld1 gene deletion a possible association with the causation of testicular tumor. We would like to emphasize that Patients with MAMLD1 mutation should be closely screened through physical examination and imaging techniques.