Persistence of müllerian duct structures in a genetic male with distal monosomy 10q

• Published in: American journal of medical genetics. Part A Vol. 167A; no. 4; pp. 791 - 796
• Main Authors: Tosur, Mustafa, Geary, Cara A., Matalon, Reuben, Radhakrishnan, Ravi S., Swischuk, Leonard E., Tarry, William F., Dong, Jianli, Lee, Phillip D. K.
• Format: Journal Article
• Language: English
• Published: United States Blackwell Publishing Ltd 01.04.2015; Wiley Subscription Services, Inc
• Subjects: 46, XY Disorders of Sex Development - diagnosis; 46, XY Disorders of Sex Development - genetics; AMH deficiency; Anti-Mullerian Hormone - deficiency; Chromosome Deletion; Chromosomes, Human, Pair 10; distal monosomy 10q; Humans; Infant; Male; Mullerian Ducts - pathology; persistent müllerian duct syndrome; persistent müllerian duct syndrome; AMH deficiency; distal monosomy 10q
• ISSN: 1552-4825; 1552-4833
• DOI: 10.1002/ajmg.a.37014

Persistent müllerian duct syndrome (PMD) with antimüllerian hormone (AMH) deficiency is usually associated with mutations or deletions of the AMH gene, although many cases have no identified gene association. We report on a genetic male with PMD and AMH deficiency associated with distal monosomy 10q. A term 3,230 g infant was born to a healthy 27‐year‐old. Fetal ultrasound had shown possible genital ambiguity. Postnatal exam showed a 0.5 cm phallus with basal meatus, normal scrotum with no palpable gonads, no vaginal orifice, and a rectal fistula with an imperforate anus. Voiding cystourethrogram with ultrasound, cystoscopy, and laparoscopy showed normal bladder, urethral orifice, distal vagina, cervix, and bilateral abdominal testis. At 24 hours of life, testosterone was within normal range with low AMH level. Chromosome microarray analysis showed 46, XY, del10(10q25.3q26.13) involving an 8.2 MB interstitial deletion. Whole exome sequencing identified a NOTCH2 variant (1p11.2). AMH sequencing revealed no abnormalities. Following multidisciplinary team and parent discussion, male gender was assigned. Testosterone treatment resulted in penile length of 1.5 cm. Bilateral orchiopexy and posterior sagittal anorectoplasty were performed at 11 months of age; rudimentary müllerian structures were identified. This observation suggests an association of 10qter elements with male differentiation including AMH expression and is similar to a patient with 46, XY, del(10q26.1) in which AMH levels were not reported. Regional candidate genes include FGFR2 (10q26.13). The possible contribution of a NOTCH2 variant cannot be excluded. © 2015 Wiley Periodicals, Inc.