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Cutis marmorata telangiectatica congenita and hypospadias: Report of 4 cases
Cutis marmorata telangiectatica congenita and hypospadias: Report of 4 cases Dan Ben-Amitai, MD,a Paul Merlob, MD,b and Aryeh Metzker, MDa Tel Aviv, Israel Cutis marmorata telangiectatica congenita (CMTC) is an uncommon sporadic congenital vascular anomaly. Of the 111 patients with CMTC examined in our clinic during the past 25 years, 4 were found to have hypospadias. All cases were sporadic. Although CMTC has been associated with various abnormalities, to our knowledge there are no reports in the literature of concurrent hypospadias. (J Am Acad Dermatol 2001;45:131-2.)
C
utis marmorata telangiectatica congenita (CMTC) is an uncommon sporadic, congenital vascular anomaly, first recognized by Van Lohuizen1 in 1922. Its major features are congenital persistent cutis marmorata, phlebectasia, telangiectasia, and occasional ulceration and skin atrophy. CMTC has been associated with various abnormalities.2 We report 4 cases of CMTC and concurrent hypospadias, to our knowledge heretofore unreported with this syndrome.
METHOD We reviewed the medical files of all 111 patients (52 males) with CMTC treated at our center during the past 25 years. Four patients, born with reticulate vascular lesions clinically diagnosed as CMTC, had a mild distal form of hypospadias (coronal and glandular) without chordee (7.69% of male live births). All cases were sporadic with no familial history of hypospadias or of CMTC. Table I summarizes the genital and cutaneous findings.
DISCUSSION Fewer than 300 cases of CMTC have been reported in the world literature to date.2,3 The first association of CMTC with congenital anomalies, namely, Sturge-Weber syndrome and patent ductus arteriosus, was described by Petrozzi, Rahn, and Mofenson4 in 1970. Associated malformations have since been From the Pediatric Dermatology Unit,a and the Department of Neonatology,b Schneider Children’s Medical Center of Israel, Petah Tiqva; and Sackler Faculty of Medicine, Tel Aviv University. Reprint requests: D. Ben-Amitai, MD, Pediatric Dermatology Unit, Schneider Children’s Medical Center of Israel, Petah Tiqva 49202, Israel. E-mail: [email protected]. Copyright © 2001 by the American Academy of Dermatology, Inc. 0190-9622/2001/$35.00 + 0 16/91/112383 doi:10.1067/mjd.2001.112383
reported in approximately 40% of the 5 largest single clinic series3,5-8 and in 68% of 126 patients in a literature review.2 A recent file study in our center9 yielded an 18.8% rate of concomitant malformations in CMTC. Regarding urogenital anomalies specifically, Del Giudice and Nydorf10 described a girl with CMTC and absence of the clitoris and urethral meatus in addition to rectovaginal and urethrovaginal fistulas. To our knowledge, the coexistence of CMTC and hypospadias has not been reported. Hypospadias, the most common anomaly of the penis, is characterized by an incomplete tubularization of the urethral plate. It has been associated with congenital anomalies11-14 and is apparently closely linked pathogenetically with other urogenital malformations.12,13 Nongenital malformations, especially midline defects, have been noted in up to 13% of patients with hypospadias,12,15 though the coexistence of hypospadias and vascular malformations is rare.16 It is well known that hypospadias is one of the most frequent congenital anomalies in neonates, with a calculated incidence of 2.3 to 29.7 per 10,000 live born infants17; in Israel, the rate is 28.5 per 10,000 infants (55.7 per 10,000 male live births). The incidence of hypospadias in our series of patients with CMTC was 7.69%, more than 13.8 times higher than that in the normal Israeli male newborn population. The high number of hypospadias cases is not a reflection of referral bias. All 4 cases of hypospadias were mild and did not belong to the highly select group of patients in our tertiary center. Therefore the simultaneous occurrence of the two defects is probably not incidental. Both CMTC and hypospadias involve intrauterine malformations. CMTC may be attributed to a developmental failure of the mesodermic vessels in the early embryonic stage. Hypospadias constitutes impaired formation of the phallus within the first 12 weeks of gestation.18 Thus we can speculate that a 131
132 Ben-Amitai, Merlob, and Metzker
J AM ACAD DERMATOL JULY 2001
Table I. Clinical data in 4 cases of cutis marmorata telangiectatica congenita and hypospadias Patient No.
Type of hypospadias
Familial hypospadias
Distribution of CMTC
Associated anomalies
Left congenital glaucoma Left hemispheric A-V malformation Left hemiatrophy None None None
1
Coronal
No
Face, neck, and left side of body
2 3 4
Coronal Glandular Glandular
No No No
Chest and upper limbs Right hand Right lower quadrant of face
common intrauterine insult may lead to both conditions. The possibility of an external etiologic factor in CMTC was supported by Rogers and Poyzer,19 who described 4 cases of CMTC occurring during an 18month period in the same geographic area, suggesting a common teratogenic agent. Others have recently hypothesized that environmental factors are involved in the origin of hypospadias.20,21 Another explanation for the association of CMTC and hypospadias is hereditary transmission. Hypospadias shows a familial tendency, due most likely to multiple gene factors.22 However, none of the 4 patients in our study had a family history of hypospadias. Heredity in CMTC has been suggested,23 but seems unlikely because of the very few reported familial cases.2 None of the 111 patients reviewed for this study had a family history of CMTC. In conclusion, there is a high incidence of hypospadias associated with CMTC. We suggest that hypospadias be added to the list of associated anomalies in patients with CMTC and that all patients with CMTC undergo a careful genitourinary examination. REFERENCES 1. Van Lohuizen CHJ. Uber eine seltene angeborene Hautanomalie (Cutis marmorata telangiectatica congenita). Acta Derm Venereol 1922;3:202-11. 2. Pehr K, Moroz B. Cutis marmorata telangiectatica congenita: Long term follow up, review of the literature and report of a case in conjunction with congenital hypothyroidism. Pediatr Dermatol 1993;10:6-11. 3. Devillers AC, de Waard-van der Spek FB, Oranje AP. Cutis marmorata telangiectatica congenita: clinical features in 35 cases. Arch Dermatol 1999;135:34-8. 4. Petrozzi JW, Rahn EK, Mofenson H. Cutis marmorata telangiectatica congenita. Arch Dermatol 1970;101:74-7. 5. Picascia DD, Esterly NB. Cutis marmorata telangiectatica congenita: report of 22 cases. J Am Acad Dermatol 1989;20:1098104. 6. South DA, Jacobs AH. Cutis marmorata telangiectatica congenita (congenital generalized phlebectasia). J Pediatr 1978;93: 944-9.
7. Kennedy C, Oranje AP, Keizer K, Van der Heuvel MM, CatsmanBerrevoets CE. Cutis marmorata telangiectatica congenita. Int J Dermatol 1992;31:249-52. 8. Powell ST, Su WPD. Cutis marmorata telangiectatica congenita: report of nine cases and review of the literature. Cutis 1984; 34:305-11. 9. Ben Amitai D, Fichman S, Merlob P, Morad Y, Lapidoth M, Metzker A. Cutis marmorata telanglectatica congenita: clinical findings in 85 patients. Pediatr Dermatol 2000;17:100-4. 10. Del Giudice SM, Nydorf ED. Cutis marmorata telangiectatica congenita with multiple congenital anomalies. Arch Dermatol 1986;122:1060-1. 11. Fallon B, Devine CJ, Horton CE. Congenital anomalies associated with hypospadias. J Urol 1976;116:585-6. 12. Shima H, Ikoma F, Terakawa T, Satoh Y, Nagata H, Shimada K, et al. Developmental anomalies associated with hypospadias. J Urol 1979;122:619-21. 13. Svensson J. Male hypospadias: 625 cases, associated malformations and possible etiological factors. Acta Pediatr Scand 1979; 68:587-92. 14. Khuri FJ, Hardy BE, Churchill BM. Urologic anomalies associated with hypospadias. Urol Clin North Am 1981;8:565-71. 15. Leung TJ, Baird PA, McGillivray B. Hypospadias in British Columbia. Am J Med Genet 1985;21:39-48. 16. Carlevar de Tiscornia A, Vignale RA, Macedo N, Cassinelli A, Realini M, Tavella N, et al. Cutaneo-visceral disseminated flat angioma, glaucoma, hypospadias and testicular ectopy. Med Cutan Ibero Lat Am 1983;11:95-8. 17. International Clearinghouse for Birth Defect Monitoring Systems. Congenital malformations worldwide. Amsterdam: Elsevier; 1991. p. 115. 18. Kluth D, Lambrecht W, Reich P. Pathogenesis of hypospadias: more questions than answers. J Pediatr Surg 1988;23:1095-101. 19. Rogers M, Poyzer KG. Cutis marmorata telangiectatica congenita. Arch Dermatol 1982;118:895-9. 20. Fredell L, Lichtenstein P, Pedersen NL, Svensson J, Nordenskjold A. Hypospadias is related to birth weight in discordant monozygotic twins. J Urol 1998;160:2197-9. 21. Carlsen E, Giwercman A, Keiding N, Skakkebaek NE. Declining semen quality and increasing incidence of testicular cancer: is there is a common cause? Environ Health Perspect 1995; 103:137-9. 22. Bauer SB, Retik AB, Colodny AH. Genetic aspects of hypospadias. Urol Clin North Am 1981;8:559-64. 23. Kurczynski TW. Hereditary cutis marmorata telangiectatica congenita. Pediatrics 1982;70:52-3.
C
utis marmorata telangiectatica congenita (CMTC) is an uncommon sporadic, congenital vascular anomaly, first recognized by Van Lohuizen1 in 1922. Its major features are congenital persistent cutis marmorata, phlebectasia, telangiectasia, and occasional ulceration and skin atrophy. CMTC has been associated with various abnormalities.2 We report 4 cases of CMTC and concurrent hypospadias, to our knowledge heretofore unreported with this syndrome.
METHOD We reviewed the medical files of all 111 patients (52 males) with CMTC treated at our center during the past 25 years. Four patients, born with reticulate vascular lesions clinically diagnosed as CMTC, had a mild distal form of hypospadias (coronal and glandular) without chordee (7.69% of male live births). All cases were sporadic with no familial history of hypospadias or of CMTC. Table I summarizes the genital and cutaneous findings.
DISCUSSION Fewer than 300 cases of CMTC have been reported in the world literature to date.2,3 The first association of CMTC with congenital anomalies, namely, Sturge-Weber syndrome and patent ductus arteriosus, was described by Petrozzi, Rahn, and Mofenson4 in 1970. Associated malformations have since been From the Pediatric Dermatology Unit,a and the Department of Neonatology,b Schneider Children’s Medical Center of Israel, Petah Tiqva; and Sackler Faculty of Medicine, Tel Aviv University. Reprint requests: D. Ben-Amitai, MD, Pediatric Dermatology Unit, Schneider Children’s Medical Center of Israel, Petah Tiqva 49202, Israel. E-mail: [email protected]. Copyright © 2001 by the American Academy of Dermatology, Inc. 0190-9622/2001/$35.00 + 0 16/91/112383 doi:10.1067/mjd.2001.112383
reported in approximately 40% of the 5 largest single clinic series3,5-8 and in 68% of 126 patients in a literature review.2 A recent file study in our center9 yielded an 18.8% rate of concomitant malformations in CMTC. Regarding urogenital anomalies specifically, Del Giudice and Nydorf10 described a girl with CMTC and absence of the clitoris and urethral meatus in addition to rectovaginal and urethrovaginal fistulas. To our knowledge, the coexistence of CMTC and hypospadias has not been reported. Hypospadias, the most common anomaly of the penis, is characterized by an incomplete tubularization of the urethral plate. It has been associated with congenital anomalies11-14 and is apparently closely linked pathogenetically with other urogenital malformations.12,13 Nongenital malformations, especially midline defects, have been noted in up to 13% of patients with hypospadias,12,15 though the coexistence of hypospadias and vascular malformations is rare.16 It is well known that hypospadias is one of the most frequent congenital anomalies in neonates, with a calculated incidence of 2.3 to 29.7 per 10,000 live born infants17; in Israel, the rate is 28.5 per 10,000 infants (55.7 per 10,000 male live births). The incidence of hypospadias in our series of patients with CMTC was 7.69%, more than 13.8 times higher than that in the normal Israeli male newborn population. The high number of hypospadias cases is not a reflection of referral bias. All 4 cases of hypospadias were mild and did not belong to the highly select group of patients in our tertiary center. Therefore the simultaneous occurrence of the two defects is probably not incidental. Both CMTC and hypospadias involve intrauterine malformations. CMTC may be attributed to a developmental failure of the mesodermic vessels in the early embryonic stage. Hypospadias constitutes impaired formation of the phallus within the first 12 weeks of gestation.18 Thus we can speculate that a 131
132 Ben-Amitai, Merlob, and Metzker
J AM ACAD DERMATOL JULY 2001
Table I. Clinical data in 4 cases of cutis marmorata telangiectatica congenita and hypospadias Patient No.
Type of hypospadias
Familial hypospadias
Distribution of CMTC
Associated anomalies
Left congenital glaucoma Left hemispheric A-V malformation Left hemiatrophy None None None
1
Coronal
No
Face, neck, and left side of body
2 3 4
Coronal Glandular Glandular
No No No
Chest and upper limbs Right hand Right lower quadrant of face
common intrauterine insult may lead to both conditions. The possibility of an external etiologic factor in CMTC was supported by Rogers and Poyzer,19 who described 4 cases of CMTC occurring during an 18month period in the same geographic area, suggesting a common teratogenic agent. Others have recently hypothesized that environmental factors are involved in the origin of hypospadias.20,21 Another explanation for the association of CMTC and hypospadias is hereditary transmission. Hypospadias shows a familial tendency, due most likely to multiple gene factors.22 However, none of the 4 patients in our study had a family history of hypospadias. Heredity in CMTC has been suggested,23 but seems unlikely because of the very few reported familial cases.2 None of the 111 patients reviewed for this study had a family history of CMTC. In conclusion, there is a high incidence of hypospadias associated with CMTC. We suggest that hypospadias be added to the list of associated anomalies in patients with CMTC and that all patients with CMTC undergo a careful genitourinary examination. REFERENCES 1. Van Lohuizen CHJ. Uber eine seltene angeborene Hautanomalie (Cutis marmorata telangiectatica congenita). Acta Derm Venereol 1922;3:202-11. 2. Pehr K, Moroz B. Cutis marmorata telangiectatica congenita: Long term follow up, review of the literature and report of a case in conjunction with congenital hypothyroidism. Pediatr Dermatol 1993;10:6-11. 3. Devillers AC, de Waard-van der Spek FB, Oranje AP. Cutis marmorata telangiectatica congenita: clinical features in 35 cases. Arch Dermatol 1999;135:34-8. 4. Petrozzi JW, Rahn EK, Mofenson H. Cutis marmorata telangiectatica congenita. Arch Dermatol 1970;101:74-7. 5. Picascia DD, Esterly NB. Cutis marmorata telangiectatica congenita: report of 22 cases. J Am Acad Dermatol 1989;20:1098104. 6. South DA, Jacobs AH. Cutis marmorata telangiectatica congenita (congenital generalized phlebectasia). J Pediatr 1978;93: 944-9.
7. Kennedy C, Oranje AP, Keizer K, Van der Heuvel MM, CatsmanBerrevoets CE. Cutis marmorata telangiectatica congenita. Int J Dermatol 1992;31:249-52. 8. Powell ST, Su WPD. Cutis marmorata telangiectatica congenita: report of nine cases and review of the literature. Cutis 1984; 34:305-11. 9. Ben Amitai D, Fichman S, Merlob P, Morad Y, Lapidoth M, Metzker A. Cutis marmorata telanglectatica congenita: clinical findings in 85 patients. Pediatr Dermatol 2000;17:100-4. 10. Del Giudice SM, Nydorf ED. Cutis marmorata telangiectatica congenita with multiple congenital anomalies. Arch Dermatol 1986;122:1060-1. 11. Fallon B, Devine CJ, Horton CE. Congenital anomalies associated with hypospadias. J Urol 1976;116:585-6. 12. Shima H, Ikoma F, Terakawa T, Satoh Y, Nagata H, Shimada K, et al. Developmental anomalies associated with hypospadias. J Urol 1979;122:619-21. 13. Svensson J. Male hypospadias: 625 cases, associated malformations and possible etiological factors. Acta Pediatr Scand 1979; 68:587-92. 14. Khuri FJ, Hardy BE, Churchill BM. Urologic anomalies associated with hypospadias. Urol Clin North Am 1981;8:565-71. 15. Leung TJ, Baird PA, McGillivray B. Hypospadias in British Columbia. Am J Med Genet 1985;21:39-48. 16. Carlevar de Tiscornia A, Vignale RA, Macedo N, Cassinelli A, Realini M, Tavella N, et al. Cutaneo-visceral disseminated flat angioma, glaucoma, hypospadias and testicular ectopy. Med Cutan Ibero Lat Am 1983;11:95-8. 17. International Clearinghouse for Birth Defect Monitoring Systems. Congenital malformations worldwide. Amsterdam: Elsevier; 1991. p. 115. 18. Kluth D, Lambrecht W, Reich P. Pathogenesis of hypospadias: more questions than answers. J Pediatr Surg 1988;23:1095-101. 19. Rogers M, Poyzer KG. Cutis marmorata telangiectatica congenita. Arch Dermatol 1982;118:895-9. 20. Fredell L, Lichtenstein P, Pedersen NL, Svensson J, Nordenskjold A. Hypospadias is related to birth weight in discordant monozygotic twins. J Urol 1998;160:2197-9. 21. Carlsen E, Giwercman A, Keiding N, Skakkebaek NE. Declining semen quality and increasing incidence of testicular cancer: is there is a common cause? Environ Health Perspect 1995; 103:137-9. 22. Bauer SB, Retik AB, Colodny AH. Genetic aspects of hypospadias. Urol Clin North Am 1981;8:559-64. 23. Kurczynski TW. Hereditary cutis marmorata telangiectatica congenita. Pediatrics 1982;70:52-3.