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Drash syndrome(DDS)

MedGen UID:
181980
Concept ID:
C0950121
Disease or Syndrome
Synonyms: DDS; Denys-Drash Syndrome; Nephropathy associated with male pseudohermaphroditism and Wilms' tumor; Nephropathy, wilms tumor, and genital anomalies; Pseudohermaphroditism, nephron disorder and Wilms' tumor; WILMS TUMOR AND PSEUDO- OR TRUE HERMAPHRODITISM; Wilms tumor and pseudohermaphroditism
SNOMED CT: Nephrotic syndrome with pseudohermaphroditism (236385009); Drash syndrome (236385009); Wilms' tumor and nephrotic syndrome with pseudohermaphroditism (236385009)
 
Gene (location): WT1 (11p13)
 
Monarch Initiative: MONDO:0008682
OMIM®: 194080
Orphanet: ORPHA220

Disease characteristics

Excerpted from the GeneReview: WT1 Disorder
WT1 disorder is characterized by congenital/infantile or childhood onset of steroid-resistant nephrotic syndrome (SRNS), a progressive glomerulopathy that does not respond to standard steroid therapy. Additional common findings can include disorders of testicular development (with or without abnormalities of the external genitalia and/or müllerian structures) and Wilms tumor. Less common findings are congenital anomalies of the kidney and urinary tract (CAKUT) and gonadoblastoma. While various combinations of renal and other findings associated with a WT1 pathogenic variant were designated as certain syndromes in the past, those designations are now recognized to be part of a phenotypic continuum and are no longer clinically helpful. [from GeneReviews]
Authors:
Beata S Lipska-Ziętkiewicz   view full author information

Additional descriptions

From OMIM
Denys-Drash syndrome (DDS) is characterized by urogenital abnormalities, progressive glomerulopathy, and the development of Wilms tumors in early childhood (summary by Antonius et al., 2008).  http://www.omim.org/entry/194080
From MedlinePlus Genetics
Denys-Drash syndrome is a condition that affects the kidneys and genitalia.

Denys-Drash syndrome is characterized by kidney disease that begins within the first few months of life. Affected individuals have a condition called diffuse glomerulosclerosis, in which scar tissue forms throughout glomeruli, which are the tiny blood vessels in the kidneys that filter waste from blood. In people with Denys-Drash syndrome, this condition often leads to kidney failure in childhood. People with Denys-Drash syndrome have an estimated 90 percent chance of developing a rare form of kidney cancer known as Wilms tumor. Affected individuals may develop multiple tumors in one or both kidneys.

Although males with Denys-Drash syndrome have the typical male chromosome pattern (46,XY), they have gonadal dysgenesis, in which external genitalia do not look clearly male or clearly female or the genitalia appear female-typical. The testes of affected males are undescended, which means they are abnormally located in the pelvis, abdomen, or groin. As a result, males with Denys-Drash are typically unable to have biological children (infertile).

Affected females usually have normal genitalia and have only the kidney features of the condition. Because they do not have all the features of the condition, females are usually given the diagnosis of isolated nephrotic syndrome.  https://medlineplus.gov/genetics/condition/denys-drash-syndrome

Clinical features

From HPO
Nephroblastoma
MedGen UID:
10221
Concept ID:
C0027708
Neoplastic Process
The presence of a nephroblastoma, which is a neoplasm of the kidney that primarily affects children.
Ovarian gonadoblastoma
MedGen UID:
309510
Concept ID:
C1518716
Neoplastic Process
The presence of a gonadoblastoma of the ovary.
Focal segmental glomerulosclerosis
MedGen UID:
4904
Concept ID:
C0017668
Disease or Syndrome
Segmental accumulation of scar tissue in individual (but not all) glomeruli.
Gonadal dysgenesis
MedGen UID:
9075
Concept ID:
C0018051
Congenital Abnormality
A congenital disorder characterized by the presence of extremely hypoplastic gonads preventing the development of secondary sex characteristics.
Kidney disorder
MedGen UID:
9635
Concept ID:
C0022658
Disease or Syndrome
A nonspecific term referring to disease or damage of the kidneys.
Nephrotic syndrome
MedGen UID:
10308
Concept ID:
C0027726
Disease or Syndrome
Nephrotic syndrome is a collection of findings resulting from glomerular dysfunction with an increase in glomerular capillary wall permeability associated with pronounced proteinuria. Nephrotic syndrome refers to the constellation of clinical findings that result from severe renal loss of protein, with Proteinuria and hypoalbuminemia, edema, and hyperlipidemia.
Male pseudohermaphroditism
MedGen UID:
68666
Concept ID:
C0238395
Congenital Abnormality
Hermaphroditism refers to a discrepancy between the morphology of the gonads and that of the external genitalia. In male pseudohermaphroditism, the genotype is male (XY) and the external genitalia are imcompletely virilized, ambiguous, or complete female. If gonads are present, they are testes.
True hermaphroditism
MedGen UID:
78595
Concept ID:
C0266361
Disease or Syndrome
The presence of both ovarian and testicular tissues either in the same or in opposite gonads. Affected persons have ambiguous genitalia and may have 46,XX or 46,XY karyotypes or 46,XX/XY mosaicism.
Uterus didelphys
MedGen UID:
82740
Concept ID:
C0266393
Congenital Abnormality
A malformation of the uterus in which the uterus is present as a paired organ as a result of the failure of fusion of the mullerian ducts during embryogenesis.
Septate vagina
MedGen UID:
82741
Concept ID:
C0266411
Congenital Abnormality
The presence of a vaginal septum, thereby creating a vaginal duplication. The septum is longitudinal in the majority of cases.
Diffuse mesangial sclerosis
MedGen UID:
78698
Concept ID:
C0268747
Disease or Syndrome
Diffuse sclerosis of the mesangium, as manifestated by diffuse mesangial matrix expansion.
Enlarged kidney
MedGen UID:
108156
Concept ID:
C0542518
Finding
An abnormal increase in the size of the kidney.
Gonadal tissue inappropriate for external genitalia or chromosomal sex
MedGen UID:
348064
Concept ID:
C1860268
Finding
Stage 5 chronic kidney disease
MedGen UID:
384526
Concept ID:
C2316810
Disease or Syndrome
A degree of kidney failure severe enough to require dialysis or kidney transplantation for survival characterized by a severe reduction in glomerular filtration rate (less than 15 ml/min/1.73 m2) and other manifestations including increased serum creatinine.
Ambiguous genitalia, male
MedGen UID:
867446
Concept ID:
C4021823
Finding
Ambiguous genitalia in an individual with XY genetic gender.
Ambiguous genitalia, female
MedGen UID:
892752
Concept ID:
C4025891
Congenital Abnormality
Ambiguous genitalia in an individual with XX genetic gender.
Hypertensive disorder
MedGen UID:
6969
Concept ID:
C0020538
Disease or Syndrome
The presence of chronic increased pressure in the systemic arterial system.
Congenital diaphragmatic hernia
MedGen UID:
68625
Concept ID:
C0235833
Congenital Abnormality
The presence of a hernia of the diaphragm present at birth.
Posterolateral diaphragmatic hernia
MedGen UID:
539426
Concept ID:
C0265700
Congenital Abnormality
A posterolateral defect in the diaphragm, commonly referred to as a Bochdalek hernia, which is often accompanied by herniation of the stomach, intestines, liver, and/or spleen into the chest cavity.
Wide anterior fontanel
MedGen UID:
400926
Concept ID:
C1866134
Finding
Enlargement of the anterior fontanelle with respect to age-dependent norms.
Neonatal respiratory distress
MedGen UID:
924182
Concept ID:
C4281993
Finding
Respiratory difficulty as newborn.
Epicanthus
MedGen UID:
151862
Concept ID:
C0678230
Congenital Abnormality
Epicanthus is a condition in which a fold of skin stretches from the upper to the lower eyelid, partially covering the inner canthus. Usher (1935) noted that epicanthus is a normal finding in the fetus of all races. Epicanthus also occurs in association with hereditary ptosis (110100).

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
Follow this link to review classifications for Drash syndrome in Orphanet.

Professional guidelines

PubMed

Meazza C, Schiavello E, Biassoni V, Podda M, Barteselli C, Barretta F, Gattuso G, Terenziani M, Ferrari A, Spreafico F, Luksch R, Casanova M, Chiaravalli S, Puma N, Bergamaschi L, Massimino M
Eur J Pediatr 2020 Sep;179(9):1353-1360. Epub 2020 Mar 5 doi: 10.1007/s00431-020-03607-6. PMID: 32140854
Millar AJW, Cox S, Davidson A
Pediatr Surg Int 2017 Jul;33(7):737-745. Epub 2017 May 17 doi: 10.1007/s00383-017-4091-6. PMID: 28516188
Millar AJ, Cox S, Davidson A
Pediatr Surg Int 2017 Apr;33(4):461-469. Epub 2017 Jan 4 doi: 10.1007/s00383-016-4047-2. PMID: 28054101

Recent clinical studies

Etiology

Meazza C, Schiavello E, Biassoni V, Podda M, Barteselli C, Barretta F, Gattuso G, Terenziani M, Ferrari A, Spreafico F, Luksch R, Casanova M, Chiaravalli S, Puma N, Bergamaschi L, Massimino M
Eur J Pediatr 2020 Sep;179(9):1353-1360. Epub 2020 Mar 5 doi: 10.1007/s00431-020-03607-6. PMID: 32140854
Nishi K, Inoguchi T, Kamei K, Hamada R, Hataya H, Ogura M, Sato M, Yoshioka T, Ogata K, Ito S, Nakanishi K, Nozu K, Hamasaki Y, Ishikura K
Clin Exp Nephrol 2019 Aug;23(8):1058-1065. Epub 2019 Apr 8 doi: 10.1007/s10157-019-01732-7. PMID: 30963316
Looijenga LH, Hersmus R, de Leeuw BH, Stoop H, Cools M, Oosterhuis JW, Drop SL, Wolffenbuttel KP
Best Pract Res Clin Endocrinol Metab 2010 Apr;24(2):291-310. doi: 10.1016/j.beem.2009.10.002. PMID: 20541153
Motoyama O, Arai K, Kawamura T, Aikawa A, Ohara T, Iitaka K, Hasegawa A
Pediatr Int 2005 Dec;47(6):607-11. doi: 10.1111/j.1442-200x.2005.02139.x. PMID: 16354210
Kucinskas L, Rudaitis S, Pundziene B, Just W
Medicina (Kaunas) 2005;41(2):132-4. PMID: 15758579

Diagnosis

Nishi K, Inoguchi T, Kamei K, Hamada R, Hataya H, Ogura M, Sato M, Yoshioka T, Ogata K, Ito S, Nakanishi K, Nozu K, Hamasaki Y, Ishikura K
Clin Exp Nephrol 2019 Aug;23(8):1058-1065. Epub 2019 Apr 8 doi: 10.1007/s10157-019-01732-7. PMID: 30963316
Millar AJW, Cox S, Davidson A
Pediatr Surg Int 2017 Jul;33(7):737-745. Epub 2017 May 17 doi: 10.1007/s00383-017-4091-6. PMID: 28516188
Motoyama O, Arai K, Kawamura T, Aikawa A, Ohara T, Iitaka K, Hasegawa A
Pediatr Int 2005 Dec;47(6):607-11. doi: 10.1111/j.1442-200x.2005.02139.x. PMID: 16354210
Kucinskas L, Rudaitis S, Pundziene B, Just W
Medicina (Kaunas) 2005;41(2):132-4. PMID: 15758579
Beckwith JB, Kiviat NB, Bonadio JF
Pediatr Pathol 1990;10(1-2):1-36. doi: 10.3109/15513819009067094. PMID: 2156243

Therapy

Ehrlich PF, Chi YY, Chintagumpala MM, Hoffer FA, Perlman EJ, Kalapurakal JA, Tornwall B, Warwick A, Shamberger RC, Khanna G, Hamilton TE, Gow KW, Paulino AC, Gratias EJ, Mullen EA, Geller JI, Grundy PE, Fernandez CV, Dome JS
Cancer 2020 Aug 1;126(15):3516-3525. Epub 2020 May 27 doi: 10.1002/cncr.32958. PMID: 32459384Free PMC Article
Millar AJ, Cox S, Davidson A
Pediatr Surg Int 2017 Apr;33(4):461-469. Epub 2017 Jan 4 doi: 10.1007/s00383-016-4047-2. PMID: 28054101
Ogawa Y, Hagiwara M
Pharmacol Ther 2012 Jun;134(3):298-305. Epub 2012 Feb 9 doi: 10.1016/j.pharmthera.2012.02.001. PMID: 22342810
Stefanidis CJ, Querfeld U
Eur J Pediatr 2011 Nov;170(11):1377-83. Epub 2011 Feb 8 doi: 10.1007/s00431-011-1397-6. PMID: 21298518
Beckwith JB, Kiviat NB, Bonadio JF
Pediatr Pathol 1990;10(1-2):1-36. doi: 10.3109/15513819009067094. PMID: 2156243

Prognosis

Nishi K, Inoguchi T, Kamei K, Hamada R, Hataya H, Ogura M, Sato M, Yoshioka T, Ogata K, Ito S, Nakanishi K, Nozu K, Hamasaki Y, Ishikura K
Clin Exp Nephrol 2019 Aug;23(8):1058-1065. Epub 2019 Apr 8 doi: 10.1007/s10157-019-01732-7. PMID: 30963316
Millar AJW, Cox S, Davidson A
Pediatr Surg Int 2017 Jul;33(7):737-745. Epub 2017 May 17 doi: 10.1007/s00383-017-4091-6. PMID: 28516188
Millar AJ, Cox S, Davidson A
Pediatr Surg Int 2017 Apr;33(4):461-469. Epub 2017 Jan 4 doi: 10.1007/s00383-016-4047-2. PMID: 28054101
Motoyama O, Arai K, Kawamura T, Aikawa A, Ohara T, Iitaka K, Hasegawa A
Pediatr Int 2005 Dec;47(6):607-11. doi: 10.1111/j.1442-200x.2005.02139.x. PMID: 16354210
Gallo GE, Chemes HE
Pediatr Pathol 1987;7(2):175-89. doi: 10.1080/15513818709177840. PMID: 2821524

Clinical prediction guides

Holl EK, Routh JC, Johnston AW, Frazier V, Rice HE, Tracy ET, Nair SK
J Pediatr Urol 2019 Oct;15(5):441.e1-441.e8. Epub 2019 Mar 20 doi: 10.1016/j.jpurol.2019.03.011. PMID: 30981637
Carson JM, Okamura K, Wakashin H, McFann K, Dobrinskikh E, Kopp JB, Blaine J
PLoS One 2014;9(6):e99771. Epub 2014 Jun 12 doi: 10.1371/journal.pone.0099771. PMID: 24924335Free PMC Article
Niaudet P, Gubler MC
Pediatr Nephrol 2006 Nov;21(11):1653-60. Epub 2006 Aug 23 doi: 10.1007/s00467-006-0208-1. PMID: 16927106
Motoyama O, Arai K, Kawamura T, Aikawa A, Ohara T, Iitaka K, Hasegawa A
Pediatr Int 2005 Dec;47(6):607-11. doi: 10.1111/j.1442-200x.2005.02139.x. PMID: 16354210
Gao F, Maiti S, Sun G, Ordonez NG, Udtha M, Deng JM, Behringer RR, Huff V
Mol Cell Biol 2004 Nov;24(22):9899-910. doi: 10.1128/MCB.24.22.9899-9910.2004. PMID: 15509792Free PMC Article

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