Mutations in the MKS1 gene can lead to two different inherited syndromes.
One of them is Meckel-Gruber syndrome which results in malformations of the central nervous system, fluid-filled sacs in the kidneys, and extra fingers and toes. Other defects like heart issues, cleft lip, cleft palate, and problems with the liver and genitalia can also occur. Unfortunately, due to the severe symptoms, individuals with Meckel-Gruber syndrome are often stillborn or pass away shortly after birth. Prenatal ultrasound can sometimes reveal these birth defects. There is no cure for Meckel-Gruber syndrome, and treatment is mainly supportive.
In some instances, mutations in MKS1 might cause a milder condition known as Bardet-Biedl syndrome (BBS13). This disorder brings about vision problems, kidney abnormalities, genital anomalies, extra fingers or toes, and mild obesity, among other symptoms. About half of those with Bardet-Biedl syndrome may experience developmental delay or mental disability. In Bardet-Biedl syndrome, surgical removal of extra fingers and toes is possible in childhood. Vision and kidney issues can be managed by medical specialists. In severe cases, kidney problems might require dialysis or transplantation. Controlling obesity through diet and exercise is recommended, and surgical correction is an option for vaginal malformations in women.
This group of conditions is caused by pathogenic (disease-causing) variants in the MKS1 gene (other genes can cause both of these conditions as well) and exhibits autosomal recessive inheritance. This means that both parents must be carriers to have a 25% chance to have a child with the condition. The risk of being a carrier is based on a person’s ancestry or ethnic background.
Resources:
Bardet-Biedl Syndrome Foundation
Medline Plus – Bardet-Biedl syndrome
Medline Plus – Meckel-Gruber syndrome
National Organization for Rare Disorders – Meckel-Gruber syndrome
Revised November 2023
