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1993-01-07-12 Hypospadias © Thomas www.thefetus.net/


Hypospadias

Dominique Thomas, MD, Muriel Brat, MD, Ernesto Comacho, MD

Adrress correspondence to Dominique Thomas, MD, Dept of Obstetrics and Gynecology, Hopital d"Ixelles CHEI 63 Rue J. Paquot, 1050 Bruxelles, Belgium. Ph: 32-2-641-4111, Fax: 32-2-641-4442

Synonyms: None.

Definition: A ventral and proximal displacement of the urethral meatus from its usual position at the tip of the glans penis2.

Prevalence: 20-82:10,000 male live births. The prevalence seems to vary between different populations, with the lowest incidence in South America1 and a rising incidence in the UK, Scandinavia and the USA.

Etiology: Abnormality of sexual differentiation of external genital primordia.

Pathogenesis: Inadequate virilization of genital tubercles and labioscrotal elements. Exposure to progestin drugs has been suggested to produce this anatomical defect3.

Complications: Deficient foreskin on the ventral aspect of the penis, microphallus, undescended testes (8-15%) and enlarged prostatic utricle. 35-50% have fibrous or cutaneous chordee. The more proximal hypospadias are associated with more severe chordee.

Associated anomalies: 2-12% have upper urinary tract anomalies19 (horseshoe kidney, renal ectopia, duplicated ureters...). Other systems are involved, depending on the chromosomal association to which they belong, in 7%21.

Differential diagnosis: None.

Recurrence risk: Hypospadias can be sporadic or due to a specific genetic cause. A few cases of familial cluster suggest that some forms may have an autosomal dominant15,16 or recessive17,18 transmission. A 14% recurrence risk for a sibling has been reported20, and 8% of affected boys have an affected father.

Management: Standard obstetrical care.

MESH Hypospadias BDE 0518 MIM 146450, 241750 ICD9 753.6 CDC 752.600

Introduction

Urinary tract abnormalities are very common features in ultrasound practice of prenatal diagnosis. We report a case of prenatal recognition of hypospadias that was associated with moderate bilateral uretero-hydronephrosis.

Case report

A 28-year-old white woman G5P4004 was scanned for routine ultrasound examination at 31 weeks of pregnancy. A single fetus was observed with normal size (biparietal diameter, abdominal circumference and femur length). We noted a bilateral pyelectasis: 9mm on the right side and 8mm on the left side. Both kidneys had upper limit size (right: 40mm length, 26mm thickness; left: 43mm length, 21 mm thickness, on longitudinal section). There was no other fetal abnormality, and amniotic fluid was normal. A repeat ultrasound examination was performed at 34 weeks (fig. 1), which confirmed bilateral pyelectasis (13 mm on the left and 19mm on the right side), enlarged kidneys and a distended left ureter (13 mm) (fig.2).

Figure 1: Bilateral pyelectasis at 34 weeks. Right: 19 mm, left: 13 mm.

Figure 2: Dilatation of the ureter. (B: bladder, R: rectum).

The bladder was normal. Male genitalia were identified (scrotum, testes and penis). During the examination, micturition occurred. The stream of urine was clearly visible by amniotic fluid turbulence (jet phenomenon4). Urine flow was identified as a discrete echogenic line in the amniotic fluid. The miction flow was perpendicular to the penal axis (fig. 3-5), which clearly indicated the presence of a hypospadias. A karyotype was obtained by amniocentesis and was normal (46XY). The patient went into spontaneous labor at 42 weeks and vaginally delivered a male infant weighing 3,700g. The examination of the neonate confirmed the presence of a hypospadias with the meatus in penoscrotal position associated with a chordee (fig. 6). Further urological investigations during the first month of life showed a bilateral hydronephrosis associated with bilateral ureterovesical junction obstruction and bilateral vesicoureteral reflux.

Figure 3: Male genitalia. Begining of micturition. The stream of urine (arrow) appears as a fluid turbulence (jet phenomenon).

Figure 4: The jet appears more clearly.

Figure 5: End of micturition: the flexed genitalias are better demonstrated.

Figure 6: Two days after birth. The chordee is more apparent than on ultrasound scans.

Discussion

Embryology

Hypospadias is due to an anomaly of the development of the penis and urethra. In the 16 mm embryo, the genital primordia show three protuberances: the genital tubercle and the two genital swellings. The urethral groove appears on the ventral side of the genital tubercle, bounded by the urethral folds. In the 45mm male embryo there is a fusion of the urethral folds over the urethral grove, which extends to the coronal sulcus of the penis. Later, the glandular urethra is formed by canalization of a cord of ectoderm. The distal glans channel tunnels to join the proximal urethra. Hypospadias is caused by a failure of closure of the urethral groove. The urethral meatus can be displaced in the normal sulcus in glandular hypospadias, in any point along the penis in penile hypospadias or in the perineum in perineal hypospadias. Closure of the urethral groove is under control of 5 alpha-dihydrotestosterone, a derivative of testosterone.

Frequently associated with hypospadias is an abnormal ventral prepuce resultant in dorsal hood and chord, which is an abnormal ventral curvature of the phallus5-8. The location of the urethral meatus is important for the possibility of an antenatal ultrasound diagnosis by recognition of the axis of the urine flow during a miction. Hypospadias is classified in four different types (fig. 7).

Figure 7: The four types of hypospadias (from left to right): glandular (60%), penile (15%), scrotal (20%) and perineal (3-5%)19.

Only the forms of hypospadias where the meatus is located in coronal sulcus or along the axis of the penis give a urine stream perpendicular to the axis of the penis in childhood9. Other features have been previously described by Hogdall13 during an ultrasound examination of a male fetus at 20 weeks who had hypospadias confirmed after birth. These are the size of genitalia and the flexed aspect of the penis. In our case, the size was considered normal and there was no evident ventral phallus incurvation.

Pathogenesis

The frequency of isolated hypospadias in the general population has led to the belief that the maternal use of progestin drugs could disturb local androgen production in fetal testicle and interfere with urethral development. This explanation is supported by the report of two cases of hypospadias among 53 male infants born as a result of assisted reproductive technology: in the two cases, vaginal suppository of natural progesterone was administered until 7 weeks and 8 weeks of pregnancy10. Oral contraceptive exposure in early pregnancy was discussed by Kallen at al11, but they did not find a demonstrable association between oral contraceptive use and infant hypospadias. In our case there was no history of hormonal exposure in early pregnancy, and it was not an isolated hypospadias, as it was associated with upper urinary tract abnormalities. This feature is unusual because the development of ureteral bud occurs earlier than the formation of the urethra7.

Associated anomalies

Hypospadias can be a feature among many other abnormalities in about 33 syndromes that have been indexed by Smith12. Prenatal sonographic identification of hypospadias can point to a syndrome present in the family.

Recurrence risk

Hypospadias can be sporadic or due to a specific genetic cause. A few cases of familial cluster suggest that some forms may have an autosomal dominant15,16 or recessive17,18 transmission. A 14% recurrence risk for a sib has been reported20, and 8% of affected boys have an affected father.

Because of the association with chromosomal abnormalities (Table 1), a karyotype should be performed.

Table 1: Syndromes that include hypospadias22.

1 4p- syndrome

1 13q- syndrome

1 Aarskog syndrome

1 Aniridia-Wilms tumor association

1 Beckwith-Wiedemann syndrome

1 de Lange syndrome

1 Dubowitz syndrome

1 Exstrophy of the cloaca sequence

1 Fanconi pancytopenia

1 Fraser syndrome

1 Hydantoin effects

1 Jarcho-Levin syndrome

1 Johanson-Blizzard syndrome

1 Lenz-Majewski hyperostosis

1 Levy-Hollister syndrome

1 Multiple lentigines

1 Opitz syndrome

1 Popliteal pterigium

1 Rapp-Hodgkin ectodermal dysplasia syndrome

1 Rieger syndrome

1 Roberts-SC phocomelia syndrome

1 Robinow syndrome

1 Rubella syndrome

1 Russel-Silver syndrome

1 Schinzel-Giedon syndrome

1 Short-rib-polydactyly syndrome

1 Sphrintzen syndrome

1 Smith-Lemli-Opitz syndrome

1 Trimethadione effects

1 Triploidy

1 Trisomy 4p syndrome

1 Trisomy 9p syndrome

1 Trisomy 13 syndrome

1 Trisomy 18 syndrome

1 Trisomy 10q (partial)

1 Valproate effects

1 VACTERL association

1 XXXXY syndrome

1 XXY syndrome

1 XYY syndrome

1 Zellweger syndrome

References

1. Kallen B, Bertollini R, Castilla E, et al.: A joint international study on the epidemiology of hypospadias. Acta Paediatr Scand (Suppl) 324:1-52,1986.

2. Jirasek JE: Development of the genital system and male pseudohermaphrodism. Cohen, ed. Baltimore. Johns Hopkins Press, 1971.

3. Calzolari E, Contiero MR, Roncarati E, Mattiuz PL, et al.: Aetiological factors in hypospadias. J Med Genet 23:333,1986.

4. Hansmann M, Hackeloer BJ, Staudach A.:Ultrasound diagnosis in obstetrics and gynecology. Springer-Verlag, Berlin, 1986.

5. Hamilton WJ, Boyd JD, Mossman HW.: Human embryology (prenatal development of form and function). W Heffer and Sons Limited, Cambridge, 1959.

6. Dennison W.: Surgery in infancy and childhood. Churchill Livingstone, Edinburgh, 1974.

7. Bellinger M,: Embryology of the male external genitalia. Urol Clin North Am 8.3:383-87,1981.

8. Kaplan GW, Borck WA.: The etiology of chordee. Urol Clin North Am 8.3:383-87,1981.

9. Bettex M, Kuffer F, Scharli A.: Precis de chirurgie infantile. Masson 1978, p.268.

10. Macnab AB, Zouves C. Hypospadias after assisted reproduction incorporating in vitro fertilization and gamete intrafallopian transfer. Fertil Steril 5:918-922,1956.

11. Kallen B, Mastroiacovo P, Lancaster P, et al: Oral contraceptives in the etiology of isolated hypospadias. Contraception 44,173-182,1991.

12. Smith DW.: Recognizable patterns of human malformation. Philadelphia: WB Saunders Company, 3rd ed, 1982, pp 639-640.

13. Hogdall G, Siegl-Bartelt J, Toi A, Ritchie S.: Prenatal diagnosis of Opitz (BBB) syndrome in the second trimester by ultrasound detection of hypospadias and hypertelorism. Prenat Diagn 9:783-793,1989.

14, Opitz TM, Summitt RL, Smith SW.: The BBB syndrome. Familial telcanthus with associated congenital anomalies. Birth Defects 2:86-94,1969.

15. Lowry RB, Kliman MR: Hypospadias in successive generations—possible dominant gene inheritance. Clin Genet 9:285-8, 1976.

16. Cote GB, Petmazaki S, Bastaskis N: A gene for hypospadias in a child with presumed tetrasomy 18p. J Med Genet 4:141-146, 1979.

17. Frydman M, Greiber C, Cohen HA: Uncomplicated familial hypospadias: evidence for autosomal recessive inheritance. Am J Med Genet 21:51-5, 1985.

18. Tsur M, Linder N, Cappis S: Hypospadias in consanguineous familly. Am J Med Genet 27:487-9, 1987.

19. Bingol N, Wasserman E: Hypospadias. In Buyse ML (Ed). Birth Defect Encyclopedia. Blackwell Scientific Publication, Cambridge MA, 1990.

20. Bauer S: Genetic aspect of hypospadias. Urol Clin North Am 8:559-71, 1981.

21. Aarskog D: Current concepts: maternal progestins as a possible cause of hypospadias. N Engl J Med 300:75-79, 1979.

22. Jones KL: Smith"s recogniable patterns of human malformation. Philadelphia: WB Saunders 1988, pp 756-7.

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