Endocrine disorder in women, characterized by high levels of male hormones (androgens) and infrequent or absent ovulation (see reproductive system). It causes a high proportion of female infertility cases. Symptoms vary but often include increased serum concentrations of androgens, insulin resistance, hirsutism, acne, and obesity. Menstruation may be irregular, absent, or excessive. The ovaries are usually enlarged and contain cysts. The disease may remain undiagnosed until a woman tries to conceive. The underlying cause is not fully understood, and no genetic mutations have been associated with the syndrome. Many women with Stein-Leventhal syndrome are at an increased risk of developing metabolic disorders such as type II diabetes or lipid disorders such as atherosclerosis at an unusually young age. Treatment attempts to reduce androgen production. Infertility may be treated with clomiphene citrate or gonadotropins to induce ovulation.
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Polycystic kidney disease (PKD, also known as polycystic kidney syndrome) is a progressive, ciliopathic, genetic disorder of the kidneys. It occurs in humans and other organisms. PKD is characterized by the presence of multiple cysts (hence, "polycystic") in both kidneys. The disease can also damage the liver, pancreas, and rarely, the heart and brain. The two major forms of polycystic kidney disease are distinguished by their patterns of inheritance.
Autosomal dominant polycystic kidney disease (ADPKD) is generally a late-onset disorder characterized by progressive cyst development and bilaterally enlarged kidneys with multiple cysts. Kidney manifestations in this disorder include renal function abnormalities, hypertension, renal pain, and renal insufficiency. Approximately 50% of patients with ADPKD have end-stage renal disease (ESRD) by the age of 60. ADPKD is a systemic disease with cysts in other organs such as the liver (which may lead to cirrhosis), seminal vesicles, pancreas, and arachnoid mater and non-cystic abnormalities such as intracranial aneurysms and dolichoectasias, dilation of the aortic root and dissection of the thoracic aorta, mitral valve prolapse, and abdominal wall hernias.
Initial simian and human symptoms are hypertension, fatigue, and mild to severe back or flank pain and urinary tract infections. The disease often leads to chronic renal failure and may result in total loss of kidney function, known as end stage renal disease (ESRD), which requires some form of renal replacement therapy (e.g. dialysis).
Autosomal recessive polycystic kidney disease (ARPKD) is much rarer than ADPKD and is often fatal in utero or during the first month of life. The signs and symptoms of the condition are usually apparent at birth or in early infancy.
The autosomal dominant form, called ADPKD (autosomal dominant PKD or "Adult-onset PKD") is much more common but less severe. In 85% of patients, ADPKD is caused by mutations in the gene PKD1 on chromosome 16 (TRPP1); in 15% of patients mutations in PKD2 (TRPP2) are causative. A third locus PKD3 is the cause of a very small percentage of cases.
The recessive form, called ARPKD (autosomal recessive polycystic kidney disease) is the less common variant. Mutations in the PKHD1 (chromosomal locus 6p12.2) cause ARPKD.
PKD and the "two hit" hypothesis:
The two hit hypothesis (aka Knudson hypothesis ) is often used to explain the manifestation of polycystic kidney disease later in life even though the mutation is present at birth. This term is borrowed from cancer research stating that both copies of the gene present in the genome have to be "silenced" before cancer manifests itself (in Knudson's case the silenced gene was Rb1). In ADPKD the original "hit" is congenital (in either the PKD1 or PKD2 genes) and the subsequent "hit" occurs later in life as the cells grow and divide. The two hit hypothesis as it relates to PKD was originally proposed by Reeders in 1992. Support for this hypothesis comes from the fact that ARPKD patients develop disease at birth, and somatic mutations in the "normal" copy of PKD1 or PKD2 have been found in cyst-lining epithelia
Recent findings in genetic research have suggested that a large number of genetic disorders, both genetic syndromes and genetic diseases, that were not previously identified in the medical literature as related, may be, in fact, highly related in the genetypical root cause of the widely-varying, phenotypically-observed disorders. Thus, PKD is a ciliopathy. Other known ciliopathies include primary ciliary dyskinesia, Bardet-Biedl syndrome, polycystic liver disease, nephronophthisis, Alstrom syndrome, Meckel-Gruber syndrome and some forms of retinal degeneration..
Molecular genetic testing by linkage analysis or direct mutation screening is available clinically; however, genetic heterogeneity is a significant complication to molecular genetic testing. Sometimes a relatively large number of affected family members need to be tested in order to establish which one of the two possible genes is responsible within each family. The large size and complexity of PKD1 and PKD2 genes, as well as marked allelic heterogeneity, present obstacles to molecular testing by direct DNA analysis. In the research setting, mutation detection rates of 50-75% have been obtained for PKD1 and ~75% for PKD2. Clinical testing of the PKD1 and PKD2 genes by direct sequence analysis is now available, with a detection rate for disease-causing mutations of 50-70%.
Genetic counseling may be helpful for families at risk for polycystic kidney disease.
There are 3 possible genotypes for PKD:
PKD DNA testing is available to identify these genotypes to help cat breeders make more informed decisions about mating patterns.