Yq Microdeletion in a Patient with VACTERL Association and Shawl Scrotum with Bifid Scrotum: A Real Pathogenetic Association or a Coincidence?

VACTERL association is defined by the occurrence of congenital malformations: vertebral defects, anal atresia, cardiac defects, tracheoesophageal fistula with esophageal atresia, radial and renal dysplasia, and limb defects. No genetic alterations have been discovered except for some sporadic chromosomal rearrangements and gene mutations. We report a boy with VACTERL association and shawl scrotum with bifid scrotum who presented with a de novo Yq11.223q11.23 microdeletion identified by array CGH. The deletion spans 3.1 Mb and encompasses several genes in the AZFc region, frequently deleted in infertile men with severe oligozoospermia or azoospermia. Herein, we discuss the possible explanation for this unusual genotype-phenotype correlation. We suggest that the deletion of the BPY2 (previously VCY2) gene, located in the AZFc region and involved in spermatogenesis, contributed to the genesis of the phenotype. In fact, BPY2 interacts with a ubiquitin-protein ligase, involved in the SHH pathway which is known to be implicated in the genesis of VACTERL association.

Diphallia, Double Bladder, and Two Hemiscrotums: A Case Report.

Complete diphallia, a rare urogenital congenital anomaly in which a male is born with two fully formed phalluses, occurs in one out of every five to six million live births. The condition is characterized by two separate phalluses, each of which comprise a pair of corpora cavernosa and one corpus spongiosum with an orthotopic urethra. Approximately 100 cases have been reported worldwide, and it is thought that each case is unique. This article discusses diphallia, urethral duplication, and bladder duplication and concludes with a case study involving a three-year-old male born to consanguineous parents from a small, remote community in Ecuador who underwent surgery for correction of a complete coronal penile and bladder duplication. After consultation, the patient was scheduled for a right penectomy and cystoplasty.

Variation in the clinical and genetic evaluation of undervirilized boys with bifid scrotum and hypospadias.

BACKGROUND: Bifid scrotum and hypospadias can be signs of undervirilization, yet boys presenting with these findings often do not undergo genetic evaluation. In some cases, identifying an underlying genetic diagnosis can help to optimize clinical care and improve guidance given to patients and families. OBJECTIVES: The aim of this study was to characterize current practice for genetic evaluation of patients with bifid scrotum, and to identify approaches with a good diagnostic yield. METHODS: A retrospective study of the Boston Children's Hospital electronic medical records (1993-2015) was conducted using the search term "bifid scrotum" and clinical data were extracted. Data were abstracted into a REDCap database for analysis. Statistical analysis was performed using SPSS, SAS, and Excel software. RESULTS: The search identified 110 subjects evaluated in the Urology and/or Endocrinology clinics for bifid scrotum. Genetic testing (including karyotype, microarray, or targeted testing) was performed on 64% of the subjects with bifid scrotum; of those tested, 23% (15% of the total cohort of 110 subjects) received a confirmed genetic diagnosis. Karyotype analysis, when performed, led to a diagnosis in 17% of patients. Of the ten instances when androgen receptor gene sequencing was performed, a pathogenic mutation was identified 20% of the time. CONCLUSION: This study demonstrated that the majority of individuals with moderate undervirilization resulting in bifid scrotum do not receive a genetic diagnosis. Over a third of the analyzed subjects did not have any genetic testing, even though karyotype analysis and androgen receptor (AR) sequencing were both relatively high yield for identifying a genetic etiology. Increased utilization of traditional genetic approaches could significantly improve the ability to find a genetic diagnosis.

Two Unrelated Undervirilized 46,XY Males with Inherited NR5A1 Variants Identified by Whole-Exome Sequencing.

BACKGROUND: Undervirilized 46,XY males with bifid scrotum often pose a diagnostic challenge, and the majority of cases typically do not receive a genetic diagnosis. NR5A1 mutations can be seen in 10-20% of the cases and are a relatively common cause of undervirilization. METHODS: Whole-exome sequencing was utilized to study 10 undervirilized 46,XY subjects with bifid scrotum. RESULTS: Exome sequencing identified novel NR5A1 variants, both affecting exon 7, in 2 of the 10 subjects with bifid scrotum. Subject 1 had a heterozygous frameshift variant, c.1150delC, p.Leu384fsTer1, within the ligand-binding domain inherited from his unaffected father. Subject 2 had a novel splice-site variant c.1139-2T>C, affecting the canonical splice acceptor site for exon 7 and also disrupting the ligand-binding domain. Both subjects had serum testosterone levels within the normal range as infants. CONCLUSIONS: We describe two novel NR5A1 variants, demonstrating mutations in this gene as a common cause of milder cases of 46,XY undervirilization. Whole-exome sequencing results yielded the diagnosis in 2 out of 10 cases without a previous diagnosis, supporting the value of this approach. Significant genotype-phenotype variability was also noted with Subject 1's paternal inheritance from his unaffected father.

Imperforate Anus with Fistula Exiting at the Penile Skin.

We present the case of a male neonate with imperforate anus and a fistula exiting on the penile skin. Anorectal malformations in boys often present themselves with an entero-perineal or entero-urinary tract fistula, the type of which is a key feature for the classification and the treatment plan. A fistula exiting in front of the scrotum, such as described in our case, is very rare and is not incorporated in the current classification and treatment algorithms. Scarce reports on misjudgment concerning the position of the blind rectal pouch in similar cases, led us to perform a colostomy instead of a one-stage correction. A posterior sagittal anorectoplasty was performed eight months later and the rectal pouch was found inside the levator sling, justifying the cautious approach. The colostomy was closed three months later and after six months the distal part of the fistula was excised. We believe that in cases with a rare fistula presentation, the position of the rectal pouch is not predictable and the surgeon should proceed with caution.

Atresia anal, fístula uretrorretal congênita, bolsa escrotal acessória e pseudo-hermafroditismo em bezerro mestiço / Anal atresia, congenital urethrorectal fistula, accessory scrotum and pseudohermafroditism in a crossbred calf

Neste trabalho, é descrito o caso de um bezerro mestiço recém-nascido que apresentava atresia anal tipo 2, fístula uretrorretal congênita, bolsa escrotal bífida e pseudo-hermafroditismo masculino. O principal sinal clínico era a eliminação de fezes por meio do óstio prepucial, uma apresentação incomum em casos de fístula uretrorretal em animais machos. Apesar de o quadro de atresia anal ser relativamente comum nessa espécie, os outros defeitos congênitos encontrados são pouco frequentes.

In this study, the case of a newborn calf, which presented type 2 anal atresia, congenital urethrorectal fistula, bifid scrotum and male pseudohermafroditism is described. The main clinical sign was the elimination of feces by the prepucial ostium, an unusual finding in cases of urethrorectal fistula in male animals. Although anal atresia is relatively common in bovines, the other congenital defects found in this case are uncommon.