Co‐occurrence of hemiscrotal agenesis with cutis marmorata telangiectatica congenita and hydronephrosis affecting the same side of the body

Abstract

To our knowledge, there are nine previous reports of patients with congenital scrotal agenesis (CSA), seven of which were bilateral, and unilateral in two, also named as hemiscrotal agenesis (HSA). Here, we report a male infant with the previously undescribed co-occurrence of HSA with cutis marmorata telangiectatica congenita (CMTC), and hydronephrosis due to vesicoureteral reflux, all of them on the left side. CMTC is a segmental vascular malformation usually attributed to mosaicism of a postzygotic mutation, whereas the mechanisms in the CSA involve a failure on the labioscrotal fold (LSF) development due to a localized 5α-reductase deficiency and/or androgen insensitivity. Since the skin with HSA was affected also by CMTC and by the fact that it exhibited lack of response to the topical testosterone treatment, all this suggests to us an androgen insensitivity mosaicism in our patient restricted to the left LSF, because skin with intact androgen receptors normally shows some type of response. Since CSA and/or HSA have been also seen in patients with PHACES, popitleal pterygium syndrome, or as part of a recently proposed familial entity with CSA (or agenesis of labia majora as its female counterpart), developmental delay, visual impairment, and moderate hearing loss, further reports could confirm this manifest genetic heterogeneity, highly evocative of somatic mosaicism in our patient.

Hemiscrotal agenesis: Pathogenesis and management strategies

“…Mohan et al ., based on two cases of complete scrotal agenesis after treatment with topical testosterone therapy, suggested that the presence of remnants of the LSF with intact androgen receptors could potentially result from a localized 5α‐reductase type 2 deficiency with enough dihydrotestosterone to prevent labia formation, but not enough to stimulate scrotal development . Corona‐Rivera et al ., in a case of hemiscrotal agenesis, suggested a localized 5α‐reductase type 2 deficiency was unlikely and that their patient had androgen insensitivity, confined to the LSF . Although the expression of these genes was only mentioned in previous reports of scrotal agenesis, we showed in the present case that scrotal skin with absent rugae and pigmentation has low activity against androgen owing to the low expression of AR and SRD5A2 .…”

“…Congenital scrotal agenesis is the rarest anomaly in scrotal development disorders, and it is characterized by the absence of scrotal rugae in the perineum between the penis and anus . In previous case reports, seven patients had bilateral scrotal agenesis, which was named complete scrotal agenesis, and three patients had unilateral scrotal agenesis, which was named hemiscrotal agenesis . However, the pathogenesis and clinical manifestations remain unclear.…”

Editorial Comment to Hemiscrotal agenesis: Pathogenesis and management strategies

“…Congenital scrotal agenesis (CSA) is a rare malformation characterized by the absence of scrotal skin, and has been previously described as a bilateral or unilateral defect in seven and four patients, respectively . From these, CSA has been part of a different pattern of defects or syndromes in six out of 11 patients, supporting the existence of genetic heterogeneity in this anomaly .…”

“…Congenital scrotal agenesis (CSA) is a rare malformation characterized by the absence of scrotal skin, and has been previously described as a bilateral or unilateral defect in seven and four patients, respectively . From these, CSA has been part of a different pattern of defects or syndromes in six out of 11 patients, supporting the existence of genetic heterogeneity in this anomaly . As the scrotum is formed by fusion of the labioscrotal folds (LSF) under androgen action, CSA it has been proposed as a primary failure of the LSF development or as a secondary consequence of a localized steroid‐5‐alpha‐reductase, alpha polypeptide 2 (SRD5A2) deficiency, or androgen insensitivity, affecting either both LSF in complete CSA .…”

“…As the scrotum is formed by fusion of the labioscrotal folds (LSF) under androgen action, CSA it has been proposed as a primary failure of the LSF development or as a secondary consequence of a localized steroid‐5‐alpha‐reductase, alpha polypeptide 2 (SRD5A2) deficiency, or androgen insensitivity, affecting either both LSF in complete CSA . The presence of a clear delimitation by a raphe in the midline in patients with unilateral or hemiscrotal agenesis shows that the arrest in the development of only one of the LSF really occurs . Topical testosterone therapy in CSA resulted in the development of normal scrotal tissue indicative of intact androgen receptors and thus, suggested a localized deficiency of SRD5A2 .…”