Med Genet 1994;31:471-477 471

Syndrome of the month J Med Genet: first published as 10.1136/jmg.31.6.471 on 1 June 1994. Downloaded from The Denys-Drash syndrome

R F Mueller

Drash et all described two unrelated children Table 1 External genitalia findings and chromosomes who presented with ambiguous genitalia, both in the Denys-Drash syndrome of whom had a unilateral Wilms' tumour, and External genitalia Chromzosomes subsequently developed progressive renal fail- Male (19 150) 46,XY 7 19 ure. Denys et aP had previously described a 46,XX 1 19 BS- 1 19 child with male pseudohermaphroditism, ND 10 19 Wilms' tumour, and a nephropathy in associ- Female (63 150) 46,XY 25 63 46,XX 155 63 ation with sex chromosomal mosaicism. Re- BS- 1,63 view of published reports shows 150 cases 64 ND 22 63 Ambiguous (65 150) 46,XY 42 65 of what has subsequently been called the 46,XX 0 65 Drash or, more correctly, the Denys-Drash 46,XX XY 1 65 BS- 8 65 syndrome.65 BS+ 1 65 ND 13 65 ? (3 150) 46,XY 2 3 ND 1 3 Clinical features GENITALIA ?= not reported, BS + - buccal smear positive negative, ND= not done. The classical presentation of the Denys-Drash syndrome is in the newborn period as a child with ambiguous genitalia. Although some of the cases of the Denys-Drash syndrome pre- nal genitalia, it is much more common for the sent with normal male external genitalia, the internal genitalia to be inappropriate, that is, vast majority will appear phenotypically fe- Wolffian structures to be present in a pheno- male or have ambiguous genitalia (table 1). typic female, or for both Mullerian and Wolf- The majority of cases of the Denys-Drash fian structures to be present. In addition, the

syndrome with any one of these three pheno- gonads are often dysgenic (streak gonads or http://jmg.bmj.com/ types of their external genitalia will have a immature, infantile, or rudimentary testicular normal male karyotype. The relative paucity of tissue) or both testicular and ovarian tissue are cases with a female karyotype may be because present or inappropriate for the external genit- of underdiagnosis of the syndrome in pheno- alia and the chromosomal sex, that is, male typic females with the nephropathy or as a pseudohermaphroditism or true hermaphrodi- result of underascertainment because of the tism.66 67

Department of previous poor survival of children with renal on September 25, 2021 by guest. Protected copyright. Clinical Genetics, failure in infancy or early childhood. Ashley Wing, The findings in the internal genitalia in the RENAL FEATURES St James's Hospital, Beckett Street, Leeds Denys-Drash syndrome are extremely variable The renal involvement in the Denys-Drash LS9 7TF, UK (table 2). While the internal genitalia in some syndrome is classically two fold; the develop- R F Mueller of the cases will be appropriate for their exter- ment of a progressive nephropathy and Wilms' tumour (table 3). The age of presentation of Table 2 Internal genitalia findings in the Denys-Drash syndrome the nephropathy is usually in the first year. The nephropathy is a primary feature as part Internal genitalia External Gonads of the syndrome and not secondary to other genitalia ? W M W+M N mechanisms as previously suggested, such as Male 15 - - ? (19/19) 1 - 2 - - Dysgenic - - 1 - - Ovaries - - - - - Testes Table 3 Renalfindings in the Denys-Drash syndrome - - - - - Absent Female 39 - - - - Nephropathy 143/150 (95%) (65/73) 7 1 8 3 2 Dysgenic* Details 104/143 2 - 2 - - Ovaries Range of age of onset 0-01 - 17 years - 1 - - - Testes Average age of onset 1 37 years - - - - - Absent Wilms' tumour laterality 111/150 (74%) Ambiguous 16 2 2 - - ? Unilateral 89/111 (80%) (62/65) 10 6 8 4 - Dysgenic* Left 15/89 - - - - - Ovaries Right 21/89 5 - 2 4 - Testes ? 53/89 2 - - - - Absent Bilateral 22/111 (20%) * Age of presentation with tumour 77/ 111 Dysgenic includes immature, infantile, rudimentary, and dysgenic testes, ovotestis, and fibrous Range 0 01-13 years streak. Average 1-65 years ? = no details, W = Wolffian derived structures, M = Mullerian d