McKusick–Kaufman syndrome

Overview

McKusick–Kaufman syndrome (MKS) is a rare, congenital genetic disorder characterized by a triad of features: hydrometrocolpos (a fluid-filled enlargement of the uterus and vagina), postaxial polydactyly (extra fingers or toes on the ulnar or fibular side), and congenital heart defects. The syndrome was first described by Dr. Victor McKusick and Dr. Robert Kaufman in the 1970s, and it most commonly affects females of Old Order Amish descent, although it has been observed in other populations.

MKS shares overlapping features with another disorder called Bardet–Biedl syndrome (BBS), and distinguishing between them, particularly in infants, can be challenging. However, MKS is generally considered less severe and does not involve progressive visual impairment or cognitive decline, which are hallmarks of BBS.

Causes

McKusick–Kaufman syndrome is caused by mutations in the MKKS gene (also known as BBS6), located on chromosome 20p12.2–p12.1. The MKKS gene provides instructions for a protein involved in the function of cilia, which are tiny, hair-like structures on the surface of cells that play a critical role in development and signaling.

MKS follows an autosomal recessive inheritance pattern, meaning that an affected child must inherit two copies of the mutated gene—one from each parent. Parents of an affected child are typically asymptomatic carriers.

Symptoms

Symptoms of McKusick–Kaufman syndrome vary depending on sex and the specific organs involved. The classical triad includes:

• Hydrometrocolpos (females):

  • Caused by vaginal outflow obstruction, often due to an imperforate hymen or vaginal atresia

  • Leads to abdominal distension in newborn girls

  • Can compress the bladder or kidneys, causing urinary tract obstruction

• Postaxial polydactyly (both sexes):

  • Presence of extra digits on the ulnar side of hands or fibular side of feet

  • Can be unilateral or bilateral

• Congenital heart defects (both sexes):

  • Include atrial septal defect (ASD), ventricular septal defect (VSD), or other structural anomalies

  • May present with cyanosis, difficulty feeding, or failure to thrive

Other possible features include:

• Renal anomalies (hydronephrosis, duplex kidneys)

• Cryptorchidism or hypospadias in males

• Respiratory distress due to abdominal mass in neonates

• Gastrointestinal symptoms due to mass effect from hydrometrocolpos

Unlike Bardet–Biedl syndrome, MKS typically does not cause intellectual disability, obesity, or progressive retinal degeneration.

Diagnosis

Diagnosis of McKusick–Kaufman syndrome is based on clinical presentation and confirmed through genetic testing. Diagnostic steps include:

• Clinical examination:

  • Identification of postaxial polydactyly at birth

  • Evaluation of abdominal distension or palpable mass in females

• Imaging studies:

  • Pelvic ultrasound or MRI to detect hydrometrocolpos and assess reproductive anatomy

  • Renal ultrasound to assess urinary tract involvement

  • Echocardiography to detect congenital heart defects

• Genetic testing:

  • Sequencing of the MKKS gene to identify pathogenic variants

  • May help distinguish from Bardet–Biedl syndrome, especially if MKKS mutations are found without other BBS features

• Family history: Especially important in populations with higher carrier frequencies, such as the Old Order Amish.

Differentiating MKS from Bardet–Biedl syndrome may require long-term follow-up, as some distinguishing features (e.g., retinal degeneration) appear later in life.

Treatment

There is no cure for McKusick–Kaufman syndrome, but many of its manifestations can be successfully treated or managed. Treatment depends on the specific abnormalities present and may include:

• Hydrometrocolpos management:

  • Surgical intervention such as hymenectomy or vaginoplasty to relieve obstruction

  • Drainage of accumulated fluid to reduce mass effect

• Polydactyly:

  • Surgical removal of extra digits for functional or cosmetic reasons, usually in infancy or early childhood

• Congenital heart defects:

  • Cardiac monitoring and surgery or medication depending on the severity of the defect

• Renal anomalies:

  • Urologic monitoring and surgical correction if needed

• Long-term follow-up:

  • Regular assessments by a multidisciplinary team including pediatricians, cardiologists, surgeons, geneticists, and urologists

Prognosis

The prognosis for individuals with McKusick–Kaufman syndrome is generally good, especially when identified early and managed appropriately. Key factors influencing outcome include:

• Timely surgical correction of hydrometrocolpos and associated anomalies

• Early detection and treatment of heart defects

• Absence of progressive neurological or retinal involvement (unlike Bardet–Biedl syndrome)

Most affected individuals can expect normal development and lifespan, particularly if complications are treated in infancy. Genetic counseling is strongly recommended for families with a history of MKS or known carrier status.