Denys–Drash syndrome (DDS) or Drash syndrome is a rare disorder or

syndrome A syndrome is a set of medical signs and symptoms which are correlated with each other and often associated with a particular disease or disorder. The word derives from the Greek σύνδρομον, meaning "concurrence". When a syndrome is paired ...

characterized by

gonadal dysgenesis Gonadal dysgenesis is classified as any congenital developmental disorder of the reproductive system in the male or female. It is the atypical development of the gonads in an embryo, with reproductive tissue replaced with functionless, fibrous ti ...

nephropathy Kidney disease, or renal disease, technically referred to as nephropathy, is damage to or disease of a kidney. Nephritis is an inflammatory kidney disease and has several types according to the location of the inflammation. Inflammation can ...

, and

Wilms' tumor Wilms' tumor or Wilms tumor, also known as nephroblastoma, is a cancer of the kidneys that typically occurs in children, rarely in adults.; and occurs most commonly as a renal tumor in child patients. It is named after Max Wilms, the German surg ...

Signs and symptoms

Clinically, Denys–Drash is characterized by the triad of

pseudohermaphroditism Pseudohermaphroditism is a condition in which an individual has a matching chromosomal and gonadal tissue (ovary or testis) sex, but mismatching external genitalia. Female pseudohermaphroditism refers to an individual with ovaries and external gen ...

mesangial The glomerulus (plural glomeruli) is a network of small blood vessels (capillaries) known as a ''tuft'', located at the beginning of a nephron in the kidney. Each of the two kidneys contains about one million nephrons. The tuft is structurally s ...

renal sclerosis, and

. The condition first manifests as early

nephrotic syndrome Nephrotic syndrome is a collection of symptoms due to kidney damage. This includes protein in the urine, low blood albumin levels, high blood lipids, and significant swelling. Other symptoms may include weight gain, feeling tired, and foamy ...

and progresses to mesangial renal sclerosis, and ultimately

kidney failure Kidney failure, also known as end-stage kidney disease, is a medical condition in which the kidneys can no longer adequately filter waste products from the blood, functioning at less than 15% of normal levels. Kidney failure is classified as eit ...

—usually within the first three years of life. The presenting characteristics of DDS include loss of playfulness, decreased appetite, weight loss,

growth delay Child development involves the biological, psychological and emotional changes that occur in human beings between birth and the conclusion of adolescence. Childhood is divided into 3 stages of life which include early childhood, middle childhood, ...

, abnormal skeletal development,

insomnia Insomnia, also known as sleeplessness, is a sleep disorder in which people have trouble sleeping. They may have difficulty falling asleep, or staying asleep as long as desired. Insomnia is typically followed by daytime sleepiness, low energy, ...

, abdominal pain,

constipation Constipation is a bowel dysfunction that makes bowel movements infrequent or hard to pass. The stool is often hard and dry. Other symptoms may include abdominal pain, bloating, and feeling as if one has not completely passed the bowel movement ...

, and

anuria Anuria is nonpassage of urine, in practice is defined as passage of less than 100Harrison's Principles of Internal Medicine, 19E PAGE 292 milliliters of urine in a day. Anuria is often caused by failure in the function of kidneys. It may also occu ...

Causes

The cause of DDS is most commonly (96% of patients) an abnormality in the

WT1 Wilms tumor protein (WT33) is a protein that in humans is encoded by the ''WT1'' gene on chromosome 11p. Function This gene encodes a transcription factor that contains four zinc finger motifs at the C-terminus and a proline / glutamine-ric ...

gene (Wilms tumor suppressor gene). These abnormalities include changes in certain

exon An exon is any part of a gene that will form a part of the final mature RNA produced by that gene after introns have been removed by RNA splicing. The term ''exon'' refers to both the DNA sequence within a gene and to the corresponding sequen ...

s (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 Chromosome 11 is one of the 23 pairs of chromosomes in humans. Humans normally have two copies of this chromosome. Chromosome 11 spans about 135 million base pairs (the building material of DNA) and represents between 4 and 4.5 percent of the tot ...

(11p13). These mutations are usually found in exons 8 or 9, but at least one has been reported in exon 4.

Mechanism

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".

History

P. Denys and Allan L. Drash first described the syndrome.

References

External links

* {{DEFAULTSORT:Denys-Drash syndrome Transcription factor deficiencies Rare diseases Syndromes affecting the kidneys Syndromes with tumors Intersex variations