McKusick-Kaufman syndrome

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McKusick-Kaufman syndrome


The McKusick-Kaufman syndrome (MKS) is a developmental disorder characterized by a group of conditions that include congenital heart disease, buildup of fluid in the female reproductive tract and extra toes and fingers.


McKusick reported the first case of a disorder which he called hydrometrocolpos syndrome in 1964. Shortly thereafter, Kaufman described another individual with a very similar group of abnormalities. Subsequent writers combined these syndromes into one, calling it the McKusick-Kaufman syndrome and characterizing its wide range of features.

MKS is the first human disorder to be attributed to a mutation occurring in a gene and affecting a type of molecule called a chaperonin. Chaperonins are sometimes called "protein cages" in that they protect cells by capturing and refolding misshapen proteins that could otherwise interfere with normal cellular functions.

Genetic profile

MKS is inherited in an autosomal recessive pattern, meaning that a child must inherit two altered genes, one from each parent, to be affected. An altered gene responsible for a rare developmental syndrome found predominantly among the Old Order Amish population has been identified. Mutations in the gene responsible for MKS have been identified on chromosome 20p12 in an Amish family. Scientists have isolated the McKusick-Kaufman syndrome gene by positional cloning.

Based on an earlier genetic analysis of the Old Order Amish population, a research group looked at a region of chromosome 20 thought to contain the gene responsible for the syndrome. A technique called sample sequencing was then used to find candidate genes in that region. One of those genes, dubbed MKS, was altered in a sample from an Amish person as well as in a sample from a non-Amish person diagnosed with MKS. In both people, errors or "misspellings" in the genetic code were found that would disturb the function of the MKS gene. It was observed that the chemical building blocks (amino acids) coded by the MKS gene appeared to be very similar to those that make up the chaperonins. Although the function of the protein made by the MKS gene is unclear as of 2001, it appears to be involved in the production of proteins associated with the development of limbs, the heart, and the reproductive system.

In 2000, researchers identified a gene mutation that causes Bardet-Biedl syndrome (BBS), a rare genetic disorder that is related to MKS. BBS is believed to be due to a complete absence of the gene responsible for MKS.


Between one and three percent of the Amish people of Lancaster County, Pennsylvania are believed to be carriers of the disease, having just one copy of the altered gene. The related Bardet-Biedl syndrome is estimated to occur between one in 125,000 and one in 160,000 people. Among an isolated community in Newfoundland, Canada, the prevalence is estimated to be ten times higher.

Signs and symptoms

Many abnormalities associated with MKS are visible in a physical exam. They include the following abnormalities:

  • Limbs: polydactyly (extra fingers or toes)
  • Genitourinary system in females: hydrometrocolpos (accumulation of fluids in the uterus and vagina), transverse vaginal membrane, vaginal atresia (absence of a vagina)
  • Genitourinary system in males: hypospadias (abnormal opening of the urinary tract), prominent scrotal raphe (ridges), micropenis, cryptorchidism (undescended testicles)
  • Cardiac: congenital heart defects
  • Head: pituitary dysplasia (abnormal development of the pituitary gland), choanal atresia (bony or membranous blockage of the passageway between the nose and pharynx), retinitis pigmentosa (overactive cells in the retina of the eye leading to blindness), tracheoesophageal fistula (abnormal passage in the throat region)
  • Skeleton: vertebral anomalies
  • Abdomen: distension, peritoneal cysts, Hirschsprung megacolon (enlarged and poorly functioning large intestine)
  • Other: nonimmune hydrops fetalis (massive build-up of fluids in a fetus or newborn)


A diagnosis of McKusick-Kaufman syndrome is usually made at birth when a newborn is given a post-natal physical exam. The diagnosis is made by noting physical abnormalities such as: polydactyly, hydrometrocolpos, a transverse vaginal membrane, vaginal atresia, hypospadias, prominent scrotal raphe, micropenis, cryptorchidism, congenital heart defects, pituitary dysplasia, choanal atresia, tracheo-esophageal fistula, vertebral anomalies, abdominal distension, peritoneal cysts, Hirschsprung megacolon, or nonimmune hydrops fetalis. The probability of a correct diagnosis increases with each additional abnormality present. A diagnosis may sometimes be confirmed with a chromosomal analysis. Abnormal development of the pituitary gland (pituitary dysplasia) and vertebral abnormalities are visible in a CT or MRI scan. Peritoneal cysts are commonly diagnosed by ultrasonography.

Treatment and management

Treatment of MKS is limited to surgical correction of defects. Timing is often important. Many abnormalities, if uncorrected, can quickly become life threatening. For example, hydrops fetalis is often fatal. Genetic counseling before marriage is recommended for persons who are possible carriers of MKS. Affected rural and Amish girls should be delivered in settings that allow rapid surgical intervention and correction of abnormalities. Such actions could be life saving.


With appropriate genetic counseling and complete family histories, individuals born with MKS can receive prompt treatment. With rapid initial surgical intervention, most of these persons can live relatively normal lives. Some abnormalities, such as hypospadias, vaginal atresia, choanal atresia, tracheo-esophageal fistula, or Hirschsprung megacolon, may require multiple operations. Due to the risk of retinitis pigmentosa, vision should be monitored closely.



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National Institutes of Health, Office of Rare Diseases. 31 Center Dr., Bldg. 31, Room 1B-19, MSC 2084, Bethesda, MD 20892-2084. (301) 402-4336. Fax: (301) 480-9655. [email protected]. <>.

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L. Fleming Fallon. Jr., MD, PhD, DrPH

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McKusick-Kaufman syndrome

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