Novel Insights from Clinical Practice Received: September 17, 2013 Accepted after revision: December 30, 2013 Published online: August 9, 2014
Fetal Diagn Ther 2015;37:70–74 DOI: 10.1159/000358592
Complete Penoscrotal Transposition: Case Report and Review of the Literature Philippa Sexton a Joseph T. Thomas b, d Scott Petersen b, d Nicole Brown b Jane E. Arms c Jenny Bryan c James Harraway c Glenn Gardener b, d
a
Department of Obstetrics and Gynaecology, b Mater Center for Maternal Fetal Medicine, and c Department of Pathology, Mater Health Services, and d School of Medicine, University of Queensland, Brisbane, Qld., Australia
Established Facts • Complete penoscrotal transposition (PST) is a recognised rare congenital abnormality with few cases since it was first recognised. • The role of genetics in this disorder is unclear.
Novel Insights • Complete PST should be included in the differential diagnosis when ambiguous genitalia are suspected on antenatal ultrasound and consideration given to combined 2D and 3D ultrasound and fetal MRI. • If complete PST is suspected, appropriate patient counseling is required, as it is most often associated with other major fetal abnormalities and a poor prognosis. • Genetic causes for complete PST need to be further investigated.
Abstract Penoscrotal transposition is a rare congenital abnormality. We report a case presenting prenatally with ambiguous genitalia and renal anomaly on obstetric ultrasound and fetal MRI and discuss the postnatal examination and autopsy findings. We present a review of the literature, including associated gene abnormalities. © 2014 S. Karger AG, Basel
© 2014 S. Karger AG, Basel 1015–3837/14/0371–0070$39.50/0 E-Mail [email protected] www.karger.com/fdt
Case Report A 22-year-old primigravida was referred at 21 weeks of gestation from a community scanning centre for tertiary level assessment with bladder not identified, oligohydramnios and cystic structures seen in the fetal abdomen. On tertiary scan, there was oligohydramnios (deepest vertical pocket less than 2 cm) and the bladder was not visualised. The kidneys were not detected in the renal fossae; however, three cystic structures were noted in the abdomen and pelvis. These structures were not seen to change in size or show peristalsis during the scan and did not have the appearance suggestive of kidneys. Though the bladder was not definitively demonstrated, the single umbilical artery was depicted passing around one of the cystic structures. Ambiguous genitalia were
Dr. Joseph T. Thomas, MBBS, FRANZCOG, DDU, C MFM Mater Center for Maternal Fetal Medicine Aubigny Place, Raymond Terrace South Brisbane, QLD 4101 (Australia) E-Mail joseph.thomas @ mater.org.au
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Key Words Ambiguous genitalia · Penoscrotal transposition · Urogenital malformation
Color version available online
a
b
d
cystic structures seen in the fetal abdomen. d Colour Doppler insonation of the three cystic structures showing cord insertion and single umbilical artery passing close to one of the cystic structures.
Color version available online
Fig. 1. Ultrasound images from a fetus presenting with absent bladder, cystic structures in the abdomen and ambiguous genitalia. a Ultrasound image showing scrotal sac but no penis. b Ultrasound image showing femurs, scrotal sac but no penis. c Three
c
b
c
d
Fig. 2. Postnatal clinical and post-mortem photographs of the neonate with complete PST. a Clinical photograph showing the scrotum without the penis. b Clinical photograph with the penis seen under the scrotal sac. c Small amount of meconium seen at the
urethral orifice and imperforate anus. d Autopsy showing multiple large bowel loops (ascending, descending, sigmoid colon and rectum) due to the recto-urethral fistula and anal atresia.
suspected with major urogenital abnormalities. However, fetal position being breech, the maternal body habitus and the oligohydramnios precluded conclusive imaging (fig. 1). A fetal MRI was performed to better define the genitalia and the suspected urogenital abnormalities. The overall impression from the fetal MRI was ‘of an obstructed upper collecting system of both kidneys with marked parenchymal thinning and cystic change’. The cystic structures noted at ultrasound were considered to represent dilated collecting systems. A tiny bladder was suspected. The genitalia were not reported on at the MRI. The differential diagnosis, based largely on the fetal MRI findings, included ‘the possibility of an obstructed horseshoe kidney or a single collecting system with obstruction and cystic changes lying adjacent to each other’. It was not possible on this fetal MRI to confirm the urogenital sinus malformation and a repeat MRI was recommended at 34 weeks. Multidisciplinary counseling was provided based on the major urogenital abnormalities. The parents declined amniocentesis as part of prenatal diagnostic testing and continued the pregnancy. Fe-
tal growth and Doppler studies were performed subsequently at 28 and 32 weeks in addition to consultations with a neonatologist, paediatric nephrologist, paediatric urologist and maternal fetal medicine specialist. There was further reduction in the amniotic fluid with no measureable amniotic fluid volume at the 32-week scan. The couple was counseled about Potter sequence and the guarded prognosis. The patient presented with a history of vaginal mucous loss at 35 weeks and established into spontaneous labour soon after, delivering a live 3,140-gram male vaginally. The neonate needed immediate resuscitation and intubation at birth. Pulmonary hypoplasia was suspected clinically given the ongoing requirement for high-frequency ventilatory support. Complete penoscrotal transposition (PST; fig. 2) with the scrotum positioned anteriorly and superior to the penis with an imperforate anus were noted; no other external dysmorphic features were noted. The neonate did not pass any urine. A small amount of meconium was passed through the phallic structure. After further multidisciplinary counseling of the parents regarding prognosis, care was redirected with neonatal death on day 5 within hours of extubation.
Complete Penoscrotal Transposition
Fetal Diagn Ther 2015;37:70–74 DOI: 10.1159/000358592
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a
Table 1. Reported cases of complete PST and the associated anomalies together with the current case
Associated anomalies genital
non-genital
Cited by Cohen-Addad [8], 1985 Appleby, 1923 Short webbed penis Hontan, 1935 Hypospadias, small penis Hinman, 1935 Long penis Huffman, 1951 No scrotal raphe, pendulous penis Burkitt, 1961 Very long penis, glans exposed McIlvoy and Harris, 1965 Narrow, long penis Remzi, 1966 Empty scrotum, long narrow penis, hypospadias Cohen-Addad [8], 1985
Carcinoma sigmoid colon Not mentioned Not mentioned Right cystic kidney, ureters opening into bowel Absent urethra, left radial aplasia, rudimentary thumb Diverticulum of prostatic ureters Bladder diverticulum
Hypospadias, absent testes
Left hydronephrosis and ureteropelvic obstruction, right ectopic kidney, cardiomegaly, trisomy 18
Cited by MacKenzie [10], 1994 Anlar, 1986 None Lage, 1987
Hypospadias
Larsen, 1990
Absent right testis, double penile urethra, ectopic scrotal skin and ‘pseudopenis’ on right ischial tuberosity None
Hall, 1992
Bilateral polycystic kidneys, ventricular septal defect, transposed aorta, hypoplastic left atrium Cystic renal dysplasia, hypoplastic left and absent right ureter, hypoplastic bladder, rectal atresia, agenesis of the lumbar spine and velamentous lumbosacral spinal cord Both kidneys on right side, lumbosacral lipoma, atrophic right lower limb Bilateral renal agenesis, imperforate anus, vertebral anomalies, oesophageal atresia, tracheo-oesophgeal fistula, congenital heart defects
MacKenzie [10], 1994
Penile torsion, penile urethral stenosis, meatal atresia, hypospadias, undescended right testis
Left polycystic dysplastic and right hydronephrotic kidney, urethral hypoplasia
Parida [13], 1995
Urethral meatus on perineum, chordee, parapenile testes No medium raphe
Imperforate anus, bilaterally small kidneys, microcephaly
Chadha [7], 1999 Kain [9], 2005 Avolio [6], 2006 Mendez-Gallart [11], 2010 Current case, 2013
Long penis, no median raphe, single testis None Small penis Small penis Hypospadias Recto-urethral fistula
A full post-mortem examination was performed. Anthropometric measurements were greater than the 90th centile for gestation. On external examination, complete PST with an imperforate anus and single umbilical artery was confirmed. At autopsy, separate dysplastic kidneys were seen low in the abdomen with bilateral pelvi-ureteric junction obstruction with secondary ureteric
72
Fetal Diagn Ther 2015;37:70–74 DOI: 10.1159/000358592
Polycystic kidneys, hypoplastic renal arteries and hydro-ureter, hypoplastic lungs, sacral agenesis, proximal thumbs Urethral atresia, radial dysgenesis None None None None Imperforate anus; bilateral pelvi-uretric junction obstruction with obstructive renal dysplasia and secondary hypoplasia of ureters and bladder; intra-abdominal right testis; large bowel obstruction; pulmonary hypoplasia and 13 thoracic vertebrae with 13 pairs of ribs
and bladder hypoplasia demonstrated. The right testis was within the abdomen. Large bowel obstruction with a narrow recto-urethral fistula was demonstrated. A remnant vitelline duct was present. Pulmonary hypoplasia was confirmed histologically. There was pathological evidence of pulmonary hypertension, a thickened and trabeculated right ventricle, and an enlarged, congested liver.
Sexton /Thomas /Petersen /Brown /Arms / Bryan /Harraway /Gardener
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First author
Bladder not visualised on ultrasound
Kidneys seen
Kidneys not seen
Normal liquor
Anhydramnios Oligohydramnios
Normal liquor
Anhydramnios Oligohydramnios
DDx: bladder exstrophy, OEIS, UGSM ± ambiguous genitalia
DDx: bilateral dysplastic kidneys, Bilateral PUJ/UVJ obstruction ± UGSM and ambiguous genitalia
DDx: ectopic kidneys, UGSM ± ambiguous genitalia
Dx: renal agenesis
‘bladder not visualised on ultrasound’ examination. OEIS = Omphalocele, exstrophy of the bladder, imperforate anus, spinal defects; UGSM = urogenital sinus malformation usually associated with cloacal malformation with or without ambiguous genitalia;
Thirteen thoracic vertebrae and rib pairs were identified. A male karyotype with no abnormality detected was confirmed on peripheral blood. DNA extracted from the post-mortem liver was analysed on the AffyMetrix CytoScan 750K SNP microarray, and no clinically significant copy number changes were detected.
Discussion and Literature Review
PST is a rare abnormality with the scrotum malpositioned anterior and superior to the penis. It can be complete with an intact scrotum positioned above the penis as in this case, or incomplete when the scrotum is not fused. PST is commonly reported in association with major, life-threatening malformations of genito-urinary, intestinal, cardiovascular and skeletal systems [1]. Neurological defects have been associated with PST [2, 3]. Most cases of PST are sporadic without evidence of maternal exposure to radiation, infection or teratogens; PST has been suggested to have a genetic aetiology [2, 4]. Whilst the ontology is not well understood, PST may be embryologically related to the complex constellation of urogenital anomalies which accompany PST. Redman and Bissada [1] suggested that PST may result from aberrant migration of the scrotal swellings secondary to abComplete Penoscrotal Transposition
PUJ = pelvi-uretric junction obstruction; UVJ = uretero-vesical junction obstruction; Dx = diagnosis. Ambiguous genitalia: when isolated, the differential diagnosis of congenital adrenal hyperplasia or androgen insensitivity syndrome needs to be considered; however, these are not associated with absent bladder.
normal positioning of the genital tubercle in the 4–5th week of gestation. In this case, the primary anomaly leading to PST may have been the complete obstruction of the upper urinary tract at the level of the pelvi-ureteric junction. It is possible that the secondary ureteric and bladder hypoplasia may then have disrupted the typical caudal/cranial orientation of the urorectal septum and genital tubercle. The disproportionate development of the colon compared to the bladder, in conjunction with rectal distention resulting from the anal atresia, may have displaced the urorectal septum in a cephalic direction. In turn then, the malpositioned urorectal septum interfered with the positioning of the genital tubercle relative to the scrotal swellings, resulting in complete PST. In 2001, Pinke et al. [2] described a series of 53 cases of surgically corrected incomplete PST, whereas there are only 20 reported cases of complete PST in the literature. The cases of incomplete PST reported by Pinke et al. [2] ranged from newborns to 30-year-old patients where multiple anomalies were detected, including recto-urethral fistula, anal atresia, and pelvi-ureteric junction obstruction and undescended testes [2]. Skeletal anomalies were also documented in their series, but not specifically 13 thoracic vertebrae, as seen in our case. They identified Fetal Diagn Ther 2015;37:70–74 DOI: 10.1159/000358592
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Fig. 3. Flow chart suggesting the differential diagnosis (DDx) when
one family in which inheritance occurred in an X-linked recessive manner postulating a genetic cause for these congenital anomalies. Other chromosomal aberrations linked to similar congenital anomalies include deletions at 13q [3–5]. Bi-allelic (recessively inherited) loss-offunction mutations in the ZBTB16 gene (chromosome 11q23) have previously been reported in a single patient, who presented with short stature, hypoplastic radii and ulnae, an additional vertebra, retarded bone age and hypoplastic genitals [5]. There are some clinical similarities between our case and this patient described by Fischer et al. [5], including genital abnormalities and an additional vertebra. However, standard cytogenetic and limited FISH analysis revealed a normal male karyotype and no abnormality was detected in the ZBTB16 gene following sequence analysis of DNA extracted from post-mortem liver. SRY gene was detected with the FISH probe [Vysis SRY (Yp11.3)] and no deletion in the 13q region was detected using the probes for 13q14 (D13s319x2) and 13q34 (qterx2). This does not exclude the possibility of a single gene disorder due to a point mutation and the family has been offered a clinical geneticist consultation. We have identified 20 reported cases of complete PST in the literature since it was first recognized in 1923 (table 1) [6–11]. No concurrent major abnormality was re-
ported in 3 of these cases, including 1 who underwent successful surgical correction [6, 9]. There were no survivors reported from the other cases. The prenatal diagnosis of PST is difficult; however, it should be considered in the differential diagnosis when ambiguous genitalia or a major urogenital abnormality is suspected. In our case, the primary reason for referral for tertiary scan was ‘bladder not seen on ultrasound’ and a flow chart for differential diagnosis has been included (fig. 3). Complete PST can be diagnosed by ultrasound in the sagittal plane when the scrotum is located above the penis; incomplete PST is identifiable in the coronal plane when the phallus is located in the middle of a divided scrotum [12]. Amnio-infusion in the context of reduced liquor, 3D/4D scanning and fetal MRI are further modalities of imaging that may increase diagnostic accuracy to help in counseling parents. Wang et al. [12] reported their experience in the prenatal diagnosis of PST. Of the 22 fetuses with suspected PST, they correctly identified 13 of 14 cases with combined 2D and 3D ultrasonography. The sensitivity with combined ultrasound was 92.9%. The identification of ambiguous genitalia at obstetric ultrasound assessment is likely to remain the main modality for suspecting PST before birth.
References
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5 Fischer S, Kohlhase J, Bohm D, Schweiger B, Hoffmann D, Heitmann M, Horsthemke B, Wieczorek D: Biallelic loss of function of the promyelocytic leukaemia zinc finger (PLZF) gene causes severe skeletal defects and genital hypoplasia. J Med Genet 2008;45:731–737. 6 Avolio L, Karmarkar SJ, Martucciello G: Complete penoscrotal transposition. Urology 2006;67:1287. 7 Chadha R, Mann V, Sharma A, Bagga D: Complete penoscrotal transposition and associated malformations. Pediatr Surg Int 1999;15:505–507. 8 Cohen-Addad N, Zarafu IW, Hanna MK: Complete penoscrotal transposition. Urology 1985;26:149–152. 9 Kain R, Arulprakash S: Complete penoscrotal transposition. Indian Pediatr 2005;42:718.
Fetal Diagn Ther 2015;37:70–74 DOI: 10.1159/000358592
10 MacKenzie J, Chitayat D, McLorie G, Balfe JW, Pandit PB, Blecher SR: Penoscrotal transposition: a case report and review. Am J Med Genet 1994;49:103–107. 11 Mendez-Gallart R, Tellado MG, Somoza I: Extreme penoscrotal transposition. World J Pediatr 2010;6:89. 12 Wang Y, Cai A, Sun J, Li T, Wang B, Li J: Prenatal diagnosis of penoscrotal transposition with 2- and 3-dimensional ultrasonography. J Ultrasound Med 2011;30:1397–1401. 13 Parida SK, Hall BD, Barton L, Fujimoto A: Penoscrotal transposition and associated anomalies: report of five new cases and review of the literature. Am J Med Genet 1995;59:68–75.
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1 Redman JF, Bissada NK: Complete penoscrotal transposition. Urology 2007;69:181–182. 2 Pinke LA, Rathbun SR, Husmann DA, Kramer SA: Penoscrotal transposition: review of 53 patients. J Urol 2001;166:1865–1868. 3 Garcia NM, Allgood J, Santos LJ, Lonergan D, Batanian JR, Henkemeyer M, Bartsch O, Schultz RA, Zinn AR, Baker LA: Deletion mapping of critical region for hypospadias, penoscrotal transposition and imperforate anus on human chromosome 13. J Pediatr Urol 2006;2:233–242. 4 Walczak-Sztulpa J, Wisniewska M, LatosBielenska A, Linne M, Kelbova C, Belitz B, Pfeiffer L, Kalscheuer V, Erdogan F, Kuss AW, Ropers HH, Ullmann R, Tzschach A: Chromosome deletions in 13q33–34: report of four patients and review of the literature. Am J Med Genet A 2008;146:337–342.
Fetal Diagn Ther 2015;37:70–74 DOI: 10.1159/000358592
Complete Penoscrotal Transposition: Case Report and Review of the Literature Philippa Sexton a Joseph T. Thomas b, d Scott Petersen b, d Nicole Brown b Jane E. Arms c Jenny Bryan c James Harraway c Glenn Gardener b, d
a
Department of Obstetrics and Gynaecology, b Mater Center for Maternal Fetal Medicine, and c Department of Pathology, Mater Health Services, and d School of Medicine, University of Queensland, Brisbane, Qld., Australia
Established Facts • Complete penoscrotal transposition (PST) is a recognised rare congenital abnormality with few cases since it was first recognised. • The role of genetics in this disorder is unclear.
Novel Insights • Complete PST should be included in the differential diagnosis when ambiguous genitalia are suspected on antenatal ultrasound and consideration given to combined 2D and 3D ultrasound and fetal MRI. • If complete PST is suspected, appropriate patient counseling is required, as it is most often associated with other major fetal abnormalities and a poor prognosis. • Genetic causes for complete PST need to be further investigated.
Abstract Penoscrotal transposition is a rare congenital abnormality. We report a case presenting prenatally with ambiguous genitalia and renal anomaly on obstetric ultrasound and fetal MRI and discuss the postnatal examination and autopsy findings. We present a review of the literature, including associated gene abnormalities. © 2014 S. Karger AG, Basel
© 2014 S. Karger AG, Basel 1015–3837/14/0371–0070$39.50/0 E-Mail [email protected] www.karger.com/fdt
Case Report A 22-year-old primigravida was referred at 21 weeks of gestation from a community scanning centre for tertiary level assessment with bladder not identified, oligohydramnios and cystic structures seen in the fetal abdomen. On tertiary scan, there was oligohydramnios (deepest vertical pocket less than 2 cm) and the bladder was not visualised. The kidneys were not detected in the renal fossae; however, three cystic structures were noted in the abdomen and pelvis. These structures were not seen to change in size or show peristalsis during the scan and did not have the appearance suggestive of kidneys. Though the bladder was not definitively demonstrated, the single umbilical artery was depicted passing around one of the cystic structures. Ambiguous genitalia were
Dr. Joseph T. Thomas, MBBS, FRANZCOG, DDU, C MFM Mater Center for Maternal Fetal Medicine Aubigny Place, Raymond Terrace South Brisbane, QLD 4101 (Australia) E-Mail joseph.thomas @ mater.org.au
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Key Words Ambiguous genitalia · Penoscrotal transposition · Urogenital malformation
Color version available online
a
b
d
cystic structures seen in the fetal abdomen. d Colour Doppler insonation of the three cystic structures showing cord insertion and single umbilical artery passing close to one of the cystic structures.
Color version available online
Fig. 1. Ultrasound images from a fetus presenting with absent bladder, cystic structures in the abdomen and ambiguous genitalia. a Ultrasound image showing scrotal sac but no penis. b Ultrasound image showing femurs, scrotal sac but no penis. c Three
c
b
c
d
Fig. 2. Postnatal clinical and post-mortem photographs of the neonate with complete PST. a Clinical photograph showing the scrotum without the penis. b Clinical photograph with the penis seen under the scrotal sac. c Small amount of meconium seen at the
urethral orifice and imperforate anus. d Autopsy showing multiple large bowel loops (ascending, descending, sigmoid colon and rectum) due to the recto-urethral fistula and anal atresia.
suspected with major urogenital abnormalities. However, fetal position being breech, the maternal body habitus and the oligohydramnios precluded conclusive imaging (fig. 1). A fetal MRI was performed to better define the genitalia and the suspected urogenital abnormalities. The overall impression from the fetal MRI was ‘of an obstructed upper collecting system of both kidneys with marked parenchymal thinning and cystic change’. The cystic structures noted at ultrasound were considered to represent dilated collecting systems. A tiny bladder was suspected. The genitalia were not reported on at the MRI. The differential diagnosis, based largely on the fetal MRI findings, included ‘the possibility of an obstructed horseshoe kidney or a single collecting system with obstruction and cystic changes lying adjacent to each other’. It was not possible on this fetal MRI to confirm the urogenital sinus malformation and a repeat MRI was recommended at 34 weeks. Multidisciplinary counseling was provided based on the major urogenital abnormalities. The parents declined amniocentesis as part of prenatal diagnostic testing and continued the pregnancy. Fe-
tal growth and Doppler studies were performed subsequently at 28 and 32 weeks in addition to consultations with a neonatologist, paediatric nephrologist, paediatric urologist and maternal fetal medicine specialist. There was further reduction in the amniotic fluid with no measureable amniotic fluid volume at the 32-week scan. The couple was counseled about Potter sequence and the guarded prognosis. The patient presented with a history of vaginal mucous loss at 35 weeks and established into spontaneous labour soon after, delivering a live 3,140-gram male vaginally. The neonate needed immediate resuscitation and intubation at birth. Pulmonary hypoplasia was suspected clinically given the ongoing requirement for high-frequency ventilatory support. Complete penoscrotal transposition (PST; fig. 2) with the scrotum positioned anteriorly and superior to the penis with an imperforate anus were noted; no other external dysmorphic features were noted. The neonate did not pass any urine. A small amount of meconium was passed through the phallic structure. After further multidisciplinary counseling of the parents regarding prognosis, care was redirected with neonatal death on day 5 within hours of extubation.
Complete Penoscrotal Transposition
Fetal Diagn Ther 2015;37:70–74 DOI: 10.1159/000358592
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a
Table 1. Reported cases of complete PST and the associated anomalies together with the current case
Associated anomalies genital
non-genital
Cited by Cohen-Addad [8], 1985 Appleby, 1923 Short webbed penis Hontan, 1935 Hypospadias, small penis Hinman, 1935 Long penis Huffman, 1951 No scrotal raphe, pendulous penis Burkitt, 1961 Very long penis, glans exposed McIlvoy and Harris, 1965 Narrow, long penis Remzi, 1966 Empty scrotum, long narrow penis, hypospadias Cohen-Addad [8], 1985
Carcinoma sigmoid colon Not mentioned Not mentioned Right cystic kidney, ureters opening into bowel Absent urethra, left radial aplasia, rudimentary thumb Diverticulum of prostatic ureters Bladder diverticulum
Hypospadias, absent testes
Left hydronephrosis and ureteropelvic obstruction, right ectopic kidney, cardiomegaly, trisomy 18
Cited by MacKenzie [10], 1994 Anlar, 1986 None Lage, 1987
Hypospadias
Larsen, 1990
Absent right testis, double penile urethra, ectopic scrotal skin and ‘pseudopenis’ on right ischial tuberosity None
Hall, 1992
Bilateral polycystic kidneys, ventricular septal defect, transposed aorta, hypoplastic left atrium Cystic renal dysplasia, hypoplastic left and absent right ureter, hypoplastic bladder, rectal atresia, agenesis of the lumbar spine and velamentous lumbosacral spinal cord Both kidneys on right side, lumbosacral lipoma, atrophic right lower limb Bilateral renal agenesis, imperforate anus, vertebral anomalies, oesophageal atresia, tracheo-oesophgeal fistula, congenital heart defects
MacKenzie [10], 1994
Penile torsion, penile urethral stenosis, meatal atresia, hypospadias, undescended right testis
Left polycystic dysplastic and right hydronephrotic kidney, urethral hypoplasia
Parida [13], 1995
Urethral meatus on perineum, chordee, parapenile testes No medium raphe
Imperforate anus, bilaterally small kidneys, microcephaly
Chadha [7], 1999 Kain [9], 2005 Avolio [6], 2006 Mendez-Gallart [11], 2010 Current case, 2013
Long penis, no median raphe, single testis None Small penis Small penis Hypospadias Recto-urethral fistula
A full post-mortem examination was performed. Anthropometric measurements were greater than the 90th centile for gestation. On external examination, complete PST with an imperforate anus and single umbilical artery was confirmed. At autopsy, separate dysplastic kidneys were seen low in the abdomen with bilateral pelvi-ureteric junction obstruction with secondary ureteric
72
Fetal Diagn Ther 2015;37:70–74 DOI: 10.1159/000358592
Polycystic kidneys, hypoplastic renal arteries and hydro-ureter, hypoplastic lungs, sacral agenesis, proximal thumbs Urethral atresia, radial dysgenesis None None None None Imperforate anus; bilateral pelvi-uretric junction obstruction with obstructive renal dysplasia and secondary hypoplasia of ureters and bladder; intra-abdominal right testis; large bowel obstruction; pulmonary hypoplasia and 13 thoracic vertebrae with 13 pairs of ribs
and bladder hypoplasia demonstrated. The right testis was within the abdomen. Large bowel obstruction with a narrow recto-urethral fistula was demonstrated. A remnant vitelline duct was present. Pulmonary hypoplasia was confirmed histologically. There was pathological evidence of pulmonary hypertension, a thickened and trabeculated right ventricle, and an enlarged, congested liver.
Sexton /Thomas /Petersen /Brown /Arms / Bryan /Harraway /Gardener
Downloaded by: Siriraj Medical Library, Mahidol University 202.28.191.34 - 2/24/2015 9:36:36 AM
First author
Bladder not visualised on ultrasound
Kidneys seen
Kidneys not seen
Normal liquor
Anhydramnios Oligohydramnios
Normal liquor
Anhydramnios Oligohydramnios
DDx: bladder exstrophy, OEIS, UGSM ± ambiguous genitalia
DDx: bilateral dysplastic kidneys, Bilateral PUJ/UVJ obstruction ± UGSM and ambiguous genitalia
DDx: ectopic kidneys, UGSM ± ambiguous genitalia
Dx: renal agenesis
‘bladder not visualised on ultrasound’ examination. OEIS = Omphalocele, exstrophy of the bladder, imperforate anus, spinal defects; UGSM = urogenital sinus malformation usually associated with cloacal malformation with or without ambiguous genitalia;
Thirteen thoracic vertebrae and rib pairs were identified. A male karyotype with no abnormality detected was confirmed on peripheral blood. DNA extracted from the post-mortem liver was analysed on the AffyMetrix CytoScan 750K SNP microarray, and no clinically significant copy number changes were detected.
Discussion and Literature Review
PST is a rare abnormality with the scrotum malpositioned anterior and superior to the penis. It can be complete with an intact scrotum positioned above the penis as in this case, or incomplete when the scrotum is not fused. PST is commonly reported in association with major, life-threatening malformations of genito-urinary, intestinal, cardiovascular and skeletal systems [1]. Neurological defects have been associated with PST [2, 3]. Most cases of PST are sporadic without evidence of maternal exposure to radiation, infection or teratogens; PST has been suggested to have a genetic aetiology [2, 4]. Whilst the ontology is not well understood, PST may be embryologically related to the complex constellation of urogenital anomalies which accompany PST. Redman and Bissada [1] suggested that PST may result from aberrant migration of the scrotal swellings secondary to abComplete Penoscrotal Transposition
PUJ = pelvi-uretric junction obstruction; UVJ = uretero-vesical junction obstruction; Dx = diagnosis. Ambiguous genitalia: when isolated, the differential diagnosis of congenital adrenal hyperplasia or androgen insensitivity syndrome needs to be considered; however, these are not associated with absent bladder.
normal positioning of the genital tubercle in the 4–5th week of gestation. In this case, the primary anomaly leading to PST may have been the complete obstruction of the upper urinary tract at the level of the pelvi-ureteric junction. It is possible that the secondary ureteric and bladder hypoplasia may then have disrupted the typical caudal/cranial orientation of the urorectal septum and genital tubercle. The disproportionate development of the colon compared to the bladder, in conjunction with rectal distention resulting from the anal atresia, may have displaced the urorectal septum in a cephalic direction. In turn then, the malpositioned urorectal septum interfered with the positioning of the genital tubercle relative to the scrotal swellings, resulting in complete PST. In 2001, Pinke et al. [2] described a series of 53 cases of surgically corrected incomplete PST, whereas there are only 20 reported cases of complete PST in the literature. The cases of incomplete PST reported by Pinke et al. [2] ranged from newborns to 30-year-old patients where multiple anomalies were detected, including recto-urethral fistula, anal atresia, and pelvi-ureteric junction obstruction and undescended testes [2]. Skeletal anomalies were also documented in their series, but not specifically 13 thoracic vertebrae, as seen in our case. They identified Fetal Diagn Ther 2015;37:70–74 DOI: 10.1159/000358592
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Fig. 3. Flow chart suggesting the differential diagnosis (DDx) when
one family in which inheritance occurred in an X-linked recessive manner postulating a genetic cause for these congenital anomalies. Other chromosomal aberrations linked to similar congenital anomalies include deletions at 13q [3–5]. Bi-allelic (recessively inherited) loss-offunction mutations in the ZBTB16 gene (chromosome 11q23) have previously been reported in a single patient, who presented with short stature, hypoplastic radii and ulnae, an additional vertebra, retarded bone age and hypoplastic genitals [5]. There are some clinical similarities between our case and this patient described by Fischer et al. [5], including genital abnormalities and an additional vertebra. However, standard cytogenetic and limited FISH analysis revealed a normal male karyotype and no abnormality was detected in the ZBTB16 gene following sequence analysis of DNA extracted from post-mortem liver. SRY gene was detected with the FISH probe [Vysis SRY (Yp11.3)] and no deletion in the 13q region was detected using the probes for 13q14 (D13s319x2) and 13q34 (qterx2). This does not exclude the possibility of a single gene disorder due to a point mutation and the family has been offered a clinical geneticist consultation. We have identified 20 reported cases of complete PST in the literature since it was first recognized in 1923 (table 1) [6–11]. No concurrent major abnormality was re-
ported in 3 of these cases, including 1 who underwent successful surgical correction [6, 9]. There were no survivors reported from the other cases. The prenatal diagnosis of PST is difficult; however, it should be considered in the differential diagnosis when ambiguous genitalia or a major urogenital abnormality is suspected. In our case, the primary reason for referral for tertiary scan was ‘bladder not seen on ultrasound’ and a flow chart for differential diagnosis has been included (fig. 3). Complete PST can be diagnosed by ultrasound in the sagittal plane when the scrotum is located above the penis; incomplete PST is identifiable in the coronal plane when the phallus is located in the middle of a divided scrotum [12]. Amnio-infusion in the context of reduced liquor, 3D/4D scanning and fetal MRI are further modalities of imaging that may increase diagnostic accuracy to help in counseling parents. Wang et al. [12] reported their experience in the prenatal diagnosis of PST. Of the 22 fetuses with suspected PST, they correctly identified 13 of 14 cases with combined 2D and 3D ultrasonography. The sensitivity with combined ultrasound was 92.9%. The identification of ambiguous genitalia at obstetric ultrasound assessment is likely to remain the main modality for suspecting PST before birth.
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