Denys–Drash syndrome

Denys–Drash syndrome
Other names: Drash syndrome

Denys–Drash syndrome (DDS) or Drash syndrome is a rare disorder or syndrome characterized by gonadal dysgenesis, nephropathy, and Wilms' tumor.

Signs and symptoms

Clinically, Denys–Drash is characterized by the triad of pseudohermaphroditism, mesangial renal sclerosis, and Wilms' tumor. The condition first manifests as early nephrotic syndrome and progresses to mesangial renal sclerosis, and ultimately kidney failure—usually within the first three years of life.

Males with Denys-Drash syndrome exhibit gonadal dysgenesis and undescended testes. Females with Denys-Drash syndrome typically have normal genitalia.[1]

The presenting characteristics of DDS include loss of playfulness, decreased appetite, weight loss, growth delay, abnormal skeletal development, insomnia, abdominal pain, constipation, and anuria.

Causes

The cause of DDS is most commonly (96% of patients) an abnormality in the WT1 gene (Wilms tumor suppressor gene). These abnormalities include changes in certain exons (9 and 8) and mutations in some alleles of the WT1 gene. Genetically, the syndrome is due to mutations in the Wilms tumor suppressor gene, WT1, which is on chromosome 11 (11p13). These mutations are usually found in exons 8 or 9, but at least one has been reported in exon 4.[2]

The condition can be inherited in an autosomal dominant pattern, but most cases occur due to new genetic mutations in people with no family history of the disorder.[1]

Diagnosis

Large, solid, expansive tumor replaced the left kidney

The evaluation of DDS is based on the following:[3]

Management

Treatment of DDS is supportive and may also include a gonadectomy and kidney transplant[3]

Prognosis

A 1994 review of 150 cases reported in the literature found that 38% had died with a mean age of death of 2 years. 32% were still alive at the time of the report with a mean age of 4.65. No data were available for the remainder. The author described living with DDS as "walking a multidimensional tight rope".[4]

History

P. Denys[5] and Allan L. Drash[6] first described the syndrome.

See also

References

  1. 1 2 "Denys-Drash syndrome". Genetic and Rare Diseases Information Center. Archived from the original on 5 January 2023. Retrieved 22 February 2023.
  2. ↑ da Silva TE, Nishi MY, Costa EM, et al. (August 2011). "A novel WT1 heterozygous nonsense mutation (p.K248X) causing a mild and slightly progressive nephropathy in a 46,XY patient with Denys–Drash syndrome". Pediatr. Nephrol. 26 (8): 1311–5. doi:10.1007/s00467-011-1847-4. PMID 21559934. S2CID 42090144.
  3. 1 2 "Denys-Drash Syndrome - Symptoms, Causes, Treatment | NORD". rarediseases.org. Archived from the original on 5 January 2023. Retrieved 20 July 2023.
  4. ↑ Mueller, R F (1994-06-01). "The Denys-Drash syndrome". Journal of Medical Genetics. 31 (6): 471–477. doi:10.1136/jmg.31.6.471. ISSN 0022-2593. PMC 1049926. PMID 8071974.
  5. ↑ Denys P, Malvaux P, Van Den Berghe H, Tanghe W, Proesmans W (1967). "[Association of an anatomo-pathological syndrome of male pseudohermaphroditism, Wilms' tumor, parenchymatous nephropathy and XX/XY mosaicism]". Arch. Fr. Pediatr. (in français). 24 (7): 729–739. PMID 4292870.
  6. ↑ Drash A, Sherman F, Hartmann WH, Blizzard RM (1970). "A syndrome of pseudohermaphroditism, Wilms' tumor, hypertension, and degenerative renal disease". J. Pediatr. 76 (4): 585–593. doi:10.1016/S0022-3476(70)80409-7. PMID 4316066.
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