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

Abstract

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.

10q26.1 Microdeletion: Redefining the critical regions for microcephaly and genital anomalies

“…Interestingly, the deletions carried by the patient described herein and by other previously reported cases, having most of these characteristics and with similar interstitial 10q26.1 deletions, do not encompass this SRO, also (Fig. , Table ) [Rooney et al, ; Irving et al, ; Mardo et al, ; Miller et al, ; Piard et al, ; Tosur et al, ].…”

Persistent Mullerian Duct Syndrome: a rare entity with a rare presentation in need of multidisciplinary management

“…It may also be undiagnosed, as in some cases the Mullerian derivatives do not give rise to any problems to the bearer. A list of the PMDS cases reported in the literature in the last five years is provided in Table-1 (4–26). And up to date, there are no reported cases of association with mental abnormality with PMDS.…”

Hearing loss, coloboma and left ventricular enlargement in a boy with an interstitial 10q26 deletion

“…All of these cases are sporadic, except five cases from two unrelated families, where the deletions were inherited from a similarly affected parent. Through comparing clinical presentation and the genomic content of the deletion in different individuals, multiple genomic regions and genes have been proposed to be responsible for specific features, such as developmental delay, intellectual disability, craniofacial features, hearing loss, neurobehavioral concerns, cardiac, and urogenital abnormalities [Piccione et al, ; Miller et al, ; Yatsenko et al, ; Iourov et al, ; Piard et al, ; Plaisancié et al, ; Choucair et al, ; Tosur et al, ; Vera‐Carbonell et al, ; Faria et al, ]. The 5.5 Mb interstitial deletion identified in our proband overlaps with ten array‐based 10q26 deletions (Fig.…”

“…Unilateral cryptorchidism is the sole genital finding in our proband. Among the males with overlapping deletions, micropenis and cryptorchidism were presented in two cases, ambiguous genitalia and cryptorchidism in three, unilateral cryptorchidism in one, and no genital anomaly were found in the other two cases [Miller et al, ; Yatsenko et al, ; Piard et al, ; Choucair et al, ; Tosur et al, ; Vera‐Carbonell et al, ; Faria et al, ]. Yatsenko et al proposed the Empty spiracles homeobox 2 gene ( EMX 2) as a candidate gene for the severe genital phenotype in their patient and prior cases (Fig.…”

“…Clinical manifestations of cases with interstitial deletions are consistent with those seen in terminal deletion cases, including psychomotor delay, intellectual disability, facial dysmorphia, hypotonia, congenital heart disease, and urogenital abnormalities. While most of the 10q26 deletions were determined by chromosome banding techniques, twenty‐three cases have been reported to date, in which the breakpoints were precisely defined by chromosomal microarray analyses [Irving et al, ; Courtens et al, ; Piccione et al, ; Miller et al, ; Yatsenko et al, ; Iourov et al, ; Piard et al, ; Plaisancié et al, ; Choucair et al, ; Tosur et al, ; Vera‐Carbonell et al, ; Faria et al, ]. Efforts have been made to delineate specific genomic regions and genes that may account for diverse clinical features seen in this deletion syndrome.…”