An international research team led by scientists at the University of Birmingham has made a genetic breakthrough in tracing the cause of a rare fatal condition, which affects unborn babies.

Research backed by BDF Newlife has identified a defective gene for Meckel-Gruber syndrome, an inherited condition that severely affects the development of the brain, liver and kidneys in an affected foetus. Babies born with the condition survive only a few hours.

The identification of a Meckel-Gruber gene opens the way for more effective screening of patients with a family history of the disease. Although Meckel-Gruber syndrome affects around one in 20,000 births, when both parents carry a defective copy of the gene there is a 1 in 4 risk of a child being born with the syndrome.

The research at the Department of Medical & Molecular Genetics at the University of Birmingham, UK, the Indiana University School of Medicine, USA, and Mayo Clinic, USA, is published on-line today in the journal, Nature Genetics

The research team worked with a number of West Midlands families, who had a family history of Meckel-Gruber to search for genetic clues to the disease. The team identified and sequenced more than twenty possible genes, without success, before eventually pinpointing the defective gene that causes the condition. Normally, when it is not defective, the newly identified gene, called MKS3, plays an important role in the development of the foetal kidney, liver and brain.

Dr Colin A. Johnson, who led the research said: “Identifying mutations in this gene, that are responsible for Meckel-Gruber syndrome, should make screening for this devastating genetic condition far easier. We also hope that understanding the genetic mechanisms that cause Meckel-Gruber syndrome will help us to more fully understand common birth defects, such as spina bifida. The problems with the development of the spinal cord, which are a feature of Meckel-Gruber syndrome, are similar to those seen in conditions like spina bifida”.

Sheila Brown OBE, the Chief Executive of BDF Newlife commented: "The incidence of this condition means that a child with the syndrome will be born approximately every 11 days in the UK. Sadly, this is a recessive disorder and it is therefore unlikely that an adult would know they carry the condition. When both parents have this gene disorder, one child in every four will be affected. This breakthrough will help screening and understanding of the devastating condition. Newlife is proud to have supported this important breakthrough with the excellent research team at Birmingham."

At the moment, Meckel-Gruber syndrome is generally picked up by an ultrasound scan between the 12th and 20th weeks of pregnancy. The research should allow the condition to be picked up at an earlier stage of pregnancy, especially for families with a history of the condition.

To request a copy of the paper or to arrange interviews contact: Ben Hill, Press Office, University of Birmingham: Tel 0121 4145134, Mob: 07789 921 163



The paper is published online in Nature Genetics:

An international team led by staff at the University of Birmingham’s Department of Medical and Molecular Genetics conducted the research. The American research was led by Mayo Clinic College of Medicine and the Indiana University School of Medicine. The research in the UK was funded by BDF Newlife the leading research charity, helping babies and families with inborn conditions, and University of Birmingham Medical School.


Meckel-Gruber syndrome is an inherited genetic disorder. Both parents must carry copies of the defective gene for their child to develop the syndrome. Research has also found that the incidence of the disease can vary between different populations.

Meckel-Gruber syndrome causes specific physical malformations:

The infant’s front “soft spot” (fontanel) is too big, which allows some of the brain and spinal fluid to bulge out (encephalocele).

The kidneys have many cysts in them (polycystic). This causes the kidneys to be too big and to not work properly.

The liver and lungs do not develop properly before birth.


The Department of Medical and Molecular Genetics is part of the University of Birmingham Medical School. The major interests of the Department are in human cancer biology, developmental genetics, molecular endocrinology and identification of recessive genes using genetic mapping. As part of the Division of Reproductive and Child Health, the Department has particular research strengths in the genetics if inherited diseases and childhood cancer.


BDF Newlife funds medical research into all inborn conditions (Birth Defects), campaigns to raise awareness and provides information and support to those affected.

BDF Newlife was formerly known as the Birth Defects Foundation and is the UK leading child health research and care charity. It was founded in 1991.

Every day in the UK as many as 124 babies are born with some sort of inborn condition. Twenty-five won’t live beyond the age of seven.

BDF Newlife funds a national nurse helpline, which offers information, and support to those affected or awaiting test results on inborn conditions. The professionally manned service is available on 08700 70 70 20 or