Pediatric Dermatology Vol. 31 No. 6 e136–e139, 2014
Split Median Raphe: Case Series and Brief Literature Review Enrico Valerio, M.D.,* and Mario Cutrone, M.D.† *Department of Woman and Child Health, Medical School, University of Padua, Padova, Italy, †Department of Pediatrics, Ospedale Dell’Angelo, Mestre, Italy
Abstract: We describe three cases of split median raphe of the penis (SMR) from our hospital newborn records from 2004 to 2013. One case was associated with median raphe cyst, one with skin hypochromia, and one with a scar-like aspect of the region of interest. SMR is thought to be the result of defective fusion of ectodermal tissue in the urethra and scrotum area or of defective growth of the perineal mesoderm around the urethra during gestation. Although SMR associated with other major penile congenital defects (epispadias, hypospadias, penile torsion, bifid scrotum, chordee) is common, isolated SMR is probably an underdiagnosed (although not rare) malformative condition. Recognizing SMR in a newborn may be of educational value to neonatologists because it leads to the search for and exclusion of the above-mentioned pathologic conditions.
Isolated split median raphe of the penis (SMR) is probably an underdescribed (although not rare) malformative condition. From 2004 to 2013 we had the opportunity to observe three cases of isolated SMR born in our hospital. Patient 1 was a full-term Nigerian boy born in 2004 who weighed 3,260 g at birth and had a small whitish cyst in the middle of the SMR (Fig. 1). Patient 2 was a full-term Bengalese boy born in 2009 who weighed 2,960 g at birth and had a hypochromic SMR and a mild bilateral hydrocele (Fig. 2). Patient 3 was a full-term Senegalese born in 2013 who weighed 3,050 g at birth with an isolated hypochromic, scar-like SMR (Fig. 3). Each patient had an otherwise normal clinical examination and was asymptomatic; all urinated normally within the first
24 hours of life. No family history was reported in our three patients. DISCUSSION The clinical records of neonates of various ethnicities (including Italian, Chinese, Romanian, Russian, Albanian, Bengalese, Senegalese, and Nigerian) born in our hospital between 2004 and 2013 were reviewed. We describe isolated SMR in three cases, all belonging to different ethnic groups but with a dark skin phototype in common. Most commonly SMR manifests itself with other commonly observed penile defects, including epispadias, hypospadias, penile torsion, and chordee.
Address correspondence to Enrico Valerio, M.D., Department of Woman and Child Health, Medical School, University of Padua, Via Giustiniani, 3, 35128 Padova, Italy, or e-mail: enrico.valerio. [email protected]. DOI: 10.1111/pde.12417
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© 2014 Wiley Periodicals, Inc.
Valerio and Cutrone: Split Median Raphe: Case Series and Brief Literature Review
Figure 1. Full-term Nigerian newborn with a split median raphe associated with a small raphe cyst.
Figure 2. Full-term Bengalese newborn with a hypochromic split median raphe associated with mild bilateral hydrocele.
Various presentations of epispadias exist, such as cloacal exstrophy, classic bladder exstrophy, and isolated epispadias. Isolated epispadias without exstrophy is the mildest form of the disease, with a prevalence of approximately 1 in 120,000 male births. This is a defect of the urethra and can affect the bladder neck, sphincter function, and pubic symphysis (1). Bladder function may be affected because of low urethral resistance during early development (2).
Figure 3. Full-term Senegalese newborn isolated, scar-like, split median raphe.
with
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an
Isolated epispadias can be differentiated into glandular, coronal, shaft, or penopubic types. In cases of isolated epispadias, the prepuce is usually absent on the dorsal side of the penis and hangs as a tag of redundant tissue on the ventral side, leaving the glans uncovered (3,4). It is uncommon for epispadias to present with an intact prepuce. At first presentation, the diagnosis of epispadias may be missed, especially if the defect is not directly visible. Based on specific clinical signs, such as a broad, spade-like glans and a dorsally directed preputial opening and urinary stream, suspicion for epispadias may arise. A gap between the corpora cavernosa may also be palpated. Furthermore, dorsal chordee and abnormalities of the penile raphe have been reported in association with epispadias (5). Hypospadias is the most common congenital anomaly of the penis, affecting 4 to 6 per 1,000 male births (6). The problem usually develops sporadically and without an obvious underlying cause. The ectopically positioned urethral meatus lies proximal to the normal site and on the ventral aspect of the penis and in severe cases opens onto the scrotum or perineum. The foreskin on the ventral surface is deficient and the foreskin on the dorsal surface is abundant, giving the appearance of a dorsal hood. Cryptorchidism and inguinal hernia are the most common associated anomalies. The frequency of associated anomalies
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increases with the severity of hypospadias (7); chordee is present in up to 70% and penile torsion in up to 15% of cases of hypospadias (8). Hypospadias is probably a multifactorial disorder; maternal exposure to estrogenic compounds interfering with the production or action of fetal androgens (9) and disrupted gene expression (10,11) have been related to this defect. Congenital penile torsion is a malformation of unknown cause characterized by a three-dimensional malrotation of the glans, corporal bodies, or both. The abnormal penile rotation is usually counterclockwise, more common on the left side (12), and often associated with other penile or urethral malformations such as chordee or hypospadias. The incidence of isolated penile torsion is 1.7% to 27%, with torsion of more than 90° reported in 0.7% of cases (13,14). Torsion of the penis can vary in severity, ranging from 30° in mild cases to 180°. It is hard to know how much of a functional problem this malformation causes in adults. Most children are asymptomatic, although the parents usually wish to correct the cosmetic defect. Repair of penile torsion, when isolated, is not recommended unless it is more than 90°. Chordee presents as a downward or, less frequently, upward curvature of the penis head. It can be congenital or acquired (e.g., as a complication of circumcision) (15). Congenital chordee is most commonly associated with hypospadias (8). Most experts agree about correcting chordee if curvature exceeds 20° (16). Isolated SMR (not associated with epispadias, hypospadias, penile torsion, or chordee) is probably an underdiagnosed condition. The only previously described case of isolated SMR in the literature is that of a 23-year-old man from India (once again with a dark skin phototype) reporting this condition from infancy, with an extension toward the scrotum starting when sexual activity started (17), whereas no previous neonatal reports are available in literature. The most common median raphe developmental isolated anomaly is the median raphe cyst (18). These cysts are due to tegumentary formation that arises as a result of “tissue trapping” during midline fusion of the ectoderm (19). When such cysts are elongated, they are known as raphe canal. During the development of external genitalia in male fetuses in the fourth month, the labioscrotal folds fuse at the midline to form the scrotum and the urethral folds fuse to enclose the penile urethra (20). The genitoperineal raphe presumably represents the superficial effects of the midline fusion of ectoderm along these areas (18). Thus SMR is probably due to
defective fusion of ectodermal tissue in the urethra and scrotum area before birth. A generally accepted theory of genital embryologic development is that the genitoperineal raphe is the result of the fusion of ectodermal tissue folds along the penis and scrotum midline. However, an alternative theory has been proposed in which an anterior growth of perineal mesoderm encloses the penile urethra, with little involvement of the genital folds (20). We do not know if isolated SMR is a milder form of other more common developmental anomalies resulting from incomplete fusion of the urethral or labioscrotal folds such as epispadias, hypospadias, or bifid scrotum (21). In our patients, there was an association between SMR and skin hypochromia/scar-like texture of the region of interest (patients 2 and 3) and between SMR and small medium raphe cyst with normal skin pigmentation (patient 1). All three patients shared a dark skin phototype. CONCLUSION Split median raphe is commonly associated with other major congenital urethral and labioscrotal folding defects such as epispadias and hypospadias. In contrast, isolated SMR, although not rare, is a possibly underdiagnosed, harmless malformative condition. We believe that recognizing SMR in a newborn may be of educational value to neonatologists because it leads to a search for and exclusion of the abovementioned pathologic conditions. REFERENCES 1. Reutter H, Shapiro E, Gruen JR. Seven new cases of familial isolated bladder exstrophy and epispadias complex (BEEC) and review of the literature. Am J Med Genet A 2003;15:215–221. 2. Grady RW, Mitchell ME. Management of epispadias. Urol Clin North Am 2002;29:349–360. 3. Sina A, Alizadeh F. Concealed male epispadias, a rare form of penile epispadias presenting as phimosis. Urol J 2011;8:328–329. 4. Bhattacharya V, Sinha JK, Tripathi FM. A rare case of epispadias with normal prepuce. Plast Reconstr Surg 1982;70:372–374. 5. Bos EM, Kuijper CF, Chrzan RJ et al. Epispadias in boys with an intact prepuce. J Pediatr Urol 2014;10:67– 73. 6. Carmichael SL, Shaw GM, Lammer EJ. Environmental and genetic contributors to hypospadias: a review of the epidemiologic evidence. Birth Defects Res A Clin Mol Teratol 2012;94:499–510. 7. Leung AK, Robson WL. Hypospadias: an update. Asian J Androl 2007;9:16–22.
Valerio and Cutrone: Split Median Raphe: Case Series and Brief Literature Review
8. Avellan L. Morphology of hypospadias. Scand J Plast Reconstr Surg 1980;14:239–247. 9. Yucel S, Cavalcanti AG, Desouza A et al. The effect of oestrogen and testosterone on the urethral seam of the developing male mouse genital tubercle. BJU Int 2003;92:1016–1021. 10. Li M, Qiu L, Lin T et al. c-Jun N-terminal kinase is upregulated in patients with hypospadias. Urology 2013;81:178–183. 11. Carmichael SL, Mohammed N, Ma C et al. Diacylglycerol kinase K variants impact hypospadias in a California study population. J Urol 2013;189:305–311. 12. Hsieh JT, Wong WY, Chen J et al. Congenital isolated penile torsion in adults: untwist with plication. Urology 2002;59:438–440. 13. Ben Ari J, Merlob P, Mimouni F et al. Characteristics of male genitalia in the newborn. J Urol 1985;134:521– 522. 14. Sarkis PE, Muthurajan S. Incidence and predictive factors of isolated neonatal penile glanular torsion. J Pediatr Urol 2007;3:495–499.
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15. Kaplan GW. Complications of circumcision. Urol Clin North Am 1983;10:543–549. 16. Bologna RA, Noah TA, Nasrallah PF et al. Chordee: varied opinions and treatments as documented in a survey of the American Academy of Pediatrics, Section of Urology. Urology 1999;53:608–612. 17. Gupta S, Kumar B. Split median raphe: a cause of concern? Sex Transm Infect 2001;77:138. 18. Little JS Jr, Keating MA, Rink RC. Median raphe cysts of the genitalia. J Urol 1992;148:1872–1873. 19. Larsen WJ. Development of the urogenital system. In Human embryology. New York: Churchill Livingstone, 1993. 20. Pellice i Vilalta C, Leulmo i Aguilar J. Cysts of the median raphe (prepuce and perineum). Brief contribution. Actas Urol Esp 1997;21:803–805. 21. Bals-Pratsch M, Schweikert HU, Nieschlag E. Androgen receptor disorders in three brothers with bifid prepenile scrotum and hypospadias. Acta Endocrinol 1990;123:271–276.
Split Median Raphe: Case Series and Brief Literature Review Enrico Valerio, M.D.,* and Mario Cutrone, M.D.† *Department of Woman and Child Health, Medical School, University of Padua, Padova, Italy, †Department of Pediatrics, Ospedale Dell’Angelo, Mestre, Italy
Abstract: We describe three cases of split median raphe of the penis (SMR) from our hospital newborn records from 2004 to 2013. One case was associated with median raphe cyst, one with skin hypochromia, and one with a scar-like aspect of the region of interest. SMR is thought to be the result of defective fusion of ectodermal tissue in the urethra and scrotum area or of defective growth of the perineal mesoderm around the urethra during gestation. Although SMR associated with other major penile congenital defects (epispadias, hypospadias, penile torsion, bifid scrotum, chordee) is common, isolated SMR is probably an underdiagnosed (although not rare) malformative condition. Recognizing SMR in a newborn may be of educational value to neonatologists because it leads to the search for and exclusion of the above-mentioned pathologic conditions.
Isolated split median raphe of the penis (SMR) is probably an underdescribed (although not rare) malformative condition. From 2004 to 2013 we had the opportunity to observe three cases of isolated SMR born in our hospital. Patient 1 was a full-term Nigerian boy born in 2004 who weighed 3,260 g at birth and had a small whitish cyst in the middle of the SMR (Fig. 1). Patient 2 was a full-term Bengalese boy born in 2009 who weighed 2,960 g at birth and had a hypochromic SMR and a mild bilateral hydrocele (Fig. 2). Patient 3 was a full-term Senegalese born in 2013 who weighed 3,050 g at birth with an isolated hypochromic, scar-like SMR (Fig. 3). Each patient had an otherwise normal clinical examination and was asymptomatic; all urinated normally within the first
24 hours of life. No family history was reported in our three patients. DISCUSSION The clinical records of neonates of various ethnicities (including Italian, Chinese, Romanian, Russian, Albanian, Bengalese, Senegalese, and Nigerian) born in our hospital between 2004 and 2013 were reviewed. We describe isolated SMR in three cases, all belonging to different ethnic groups but with a dark skin phototype in common. Most commonly SMR manifests itself with other commonly observed penile defects, including epispadias, hypospadias, penile torsion, and chordee.
Address correspondence to Enrico Valerio, M.D., Department of Woman and Child Health, Medical School, University of Padua, Via Giustiniani, 3, 35128 Padova, Italy, or e-mail: enrico.valerio. [email protected]. DOI: 10.1111/pde.12417
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© 2014 Wiley Periodicals, Inc.
Valerio and Cutrone: Split Median Raphe: Case Series and Brief Literature Review
Figure 1. Full-term Nigerian newborn with a split median raphe associated with a small raphe cyst.
Figure 2. Full-term Bengalese newborn with a hypochromic split median raphe associated with mild bilateral hydrocele.
Various presentations of epispadias exist, such as cloacal exstrophy, classic bladder exstrophy, and isolated epispadias. Isolated epispadias without exstrophy is the mildest form of the disease, with a prevalence of approximately 1 in 120,000 male births. This is a defect of the urethra and can affect the bladder neck, sphincter function, and pubic symphysis (1). Bladder function may be affected because of low urethral resistance during early development (2).
Figure 3. Full-term Senegalese newborn isolated, scar-like, split median raphe.
with
e137
an
Isolated epispadias can be differentiated into glandular, coronal, shaft, or penopubic types. In cases of isolated epispadias, the prepuce is usually absent on the dorsal side of the penis and hangs as a tag of redundant tissue on the ventral side, leaving the glans uncovered (3,4). It is uncommon for epispadias to present with an intact prepuce. At first presentation, the diagnosis of epispadias may be missed, especially if the defect is not directly visible. Based on specific clinical signs, such as a broad, spade-like glans and a dorsally directed preputial opening and urinary stream, suspicion for epispadias may arise. A gap between the corpora cavernosa may also be palpated. Furthermore, dorsal chordee and abnormalities of the penile raphe have been reported in association with epispadias (5). Hypospadias is the most common congenital anomaly of the penis, affecting 4 to 6 per 1,000 male births (6). The problem usually develops sporadically and without an obvious underlying cause. The ectopically positioned urethral meatus lies proximal to the normal site and on the ventral aspect of the penis and in severe cases opens onto the scrotum or perineum. The foreskin on the ventral surface is deficient and the foreskin on the dorsal surface is abundant, giving the appearance of a dorsal hood. Cryptorchidism and inguinal hernia are the most common associated anomalies. The frequency of associated anomalies
e138 Pediatric Dermatology Vol. 31 No. 6 November/December 2014
increases with the severity of hypospadias (7); chordee is present in up to 70% and penile torsion in up to 15% of cases of hypospadias (8). Hypospadias is probably a multifactorial disorder; maternal exposure to estrogenic compounds interfering with the production or action of fetal androgens (9) and disrupted gene expression (10,11) have been related to this defect. Congenital penile torsion is a malformation of unknown cause characterized by a three-dimensional malrotation of the glans, corporal bodies, or both. The abnormal penile rotation is usually counterclockwise, more common on the left side (12), and often associated with other penile or urethral malformations such as chordee or hypospadias. The incidence of isolated penile torsion is 1.7% to 27%, with torsion of more than 90° reported in 0.7% of cases (13,14). Torsion of the penis can vary in severity, ranging from 30° in mild cases to 180°. It is hard to know how much of a functional problem this malformation causes in adults. Most children are asymptomatic, although the parents usually wish to correct the cosmetic defect. Repair of penile torsion, when isolated, is not recommended unless it is more than 90°. Chordee presents as a downward or, less frequently, upward curvature of the penis head. It can be congenital or acquired (e.g., as a complication of circumcision) (15). Congenital chordee is most commonly associated with hypospadias (8). Most experts agree about correcting chordee if curvature exceeds 20° (16). Isolated SMR (not associated with epispadias, hypospadias, penile torsion, or chordee) is probably an underdiagnosed condition. The only previously described case of isolated SMR in the literature is that of a 23-year-old man from India (once again with a dark skin phototype) reporting this condition from infancy, with an extension toward the scrotum starting when sexual activity started (17), whereas no previous neonatal reports are available in literature. The most common median raphe developmental isolated anomaly is the median raphe cyst (18). These cysts are due to tegumentary formation that arises as a result of “tissue trapping” during midline fusion of the ectoderm (19). When such cysts are elongated, they are known as raphe canal. During the development of external genitalia in male fetuses in the fourth month, the labioscrotal folds fuse at the midline to form the scrotum and the urethral folds fuse to enclose the penile urethra (20). The genitoperineal raphe presumably represents the superficial effects of the midline fusion of ectoderm along these areas (18). Thus SMR is probably due to
defective fusion of ectodermal tissue in the urethra and scrotum area before birth. A generally accepted theory of genital embryologic development is that the genitoperineal raphe is the result of the fusion of ectodermal tissue folds along the penis and scrotum midline. However, an alternative theory has been proposed in which an anterior growth of perineal mesoderm encloses the penile urethra, with little involvement of the genital folds (20). We do not know if isolated SMR is a milder form of other more common developmental anomalies resulting from incomplete fusion of the urethral or labioscrotal folds such as epispadias, hypospadias, or bifid scrotum (21). In our patients, there was an association between SMR and skin hypochromia/scar-like texture of the region of interest (patients 2 and 3) and between SMR and small medium raphe cyst with normal skin pigmentation (patient 1). All three patients shared a dark skin phototype. CONCLUSION Split median raphe is commonly associated with other major congenital urethral and labioscrotal folding defects such as epispadias and hypospadias. In contrast, isolated SMR, although not rare, is a possibly underdiagnosed, harmless malformative condition. We believe that recognizing SMR in a newborn may be of educational value to neonatologists because it leads to a search for and exclusion of the abovementioned pathologic conditions. REFERENCES 1. Reutter H, Shapiro E, Gruen JR. Seven new cases of familial isolated bladder exstrophy and epispadias complex (BEEC) and review of the literature. Am J Med Genet A 2003;15:215–221. 2. Grady RW, Mitchell ME. Management of epispadias. Urol Clin North Am 2002;29:349–360. 3. Sina A, Alizadeh F. Concealed male epispadias, a rare form of penile epispadias presenting as phimosis. Urol J 2011;8:328–329. 4. Bhattacharya V, Sinha JK, Tripathi FM. A rare case of epispadias with normal prepuce. Plast Reconstr Surg 1982;70:372–374. 5. Bos EM, Kuijper CF, Chrzan RJ et al. Epispadias in boys with an intact prepuce. J Pediatr Urol 2014;10:67– 73. 6. Carmichael SL, Shaw GM, Lammer EJ. Environmental and genetic contributors to hypospadias: a review of the epidemiologic evidence. Birth Defects Res A Clin Mol Teratol 2012;94:499–510. 7. Leung AK, Robson WL. Hypospadias: an update. Asian J Androl 2007;9:16–22.
Valerio and Cutrone: Split Median Raphe: Case Series and Brief Literature Review
8. Avellan L. Morphology of hypospadias. Scand J Plast Reconstr Surg 1980;14:239–247. 9. Yucel S, Cavalcanti AG, Desouza A et al. The effect of oestrogen and testosterone on the urethral seam of the developing male mouse genital tubercle. BJU Int 2003;92:1016–1021. 10. Li M, Qiu L, Lin T et al. c-Jun N-terminal kinase is upregulated in patients with hypospadias. Urology 2013;81:178–183. 11. Carmichael SL, Mohammed N, Ma C et al. Diacylglycerol kinase K variants impact hypospadias in a California study population. J Urol 2013;189:305–311. 12. Hsieh JT, Wong WY, Chen J et al. Congenital isolated penile torsion in adults: untwist with plication. Urology 2002;59:438–440. 13. Ben Ari J, Merlob P, Mimouni F et al. Characteristics of male genitalia in the newborn. J Urol 1985;134:521– 522. 14. Sarkis PE, Muthurajan S. Incidence and predictive factors of isolated neonatal penile glanular torsion. J Pediatr Urol 2007;3:495–499.
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15. Kaplan GW. Complications of circumcision. Urol Clin North Am 1983;10:543–549. 16. Bologna RA, Noah TA, Nasrallah PF et al. Chordee: varied opinions and treatments as documented in a survey of the American Academy of Pediatrics, Section of Urology. Urology 1999;53:608–612. 17. Gupta S, Kumar B. Split median raphe: a cause of concern? Sex Transm Infect 2001;77:138. 18. Little JS Jr, Keating MA, Rink RC. Median raphe cysts of the genitalia. J Urol 1992;148:1872–1873. 19. Larsen WJ. Development of the urogenital system. In Human embryology. New York: Churchill Livingstone, 1993. 20. Pellice i Vilalta C, Leulmo i Aguilar J. Cysts of the median raphe (prepuce and perineum). Brief contribution. Actas Urol Esp 1997;21:803–805. 21. Bals-Pratsch M, Schweikert HU, Nieschlag E. Androgen receptor disorders in three brothers with bifid prepenile scrotum and hypospadias. Acta Endocrinol 1990;123:271–276.
