Meckel-Gruber Syndrome

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Meckel-Gruber syndrome


Meckel-Gruber syndrome (MGS) is an inherited condition that causes skull abnormality, enlarged cystic kidneys, liver damage, and extra fingers and toes. Findings vary between affected infants (even in the same family), as well as between ethnic groups. Infants with MGS are usually stillborn or die shortly after birth.


The first reports of MGS were published in 1822 by Johann Friedrich Meckel. G. B. Gruber also published reports of MGS patients in 1934 and gave it the name dysencephalia splanchnocystica. MGS is also known as Meckel syndrome and Gruber syndrome.

MGS affects many different organ systems including the central nervous system (brain and spinal cord), face, kidneys, liver, fingers and toes, and occasionally the bones of the arms and legs. Some researchers believe that abnormal development and differentiation of the embryonic mesoderm (the early tissue layer that contributes to the formation of the bones, cartilage, muscles, reproductive system, blood cells, heart, and kidneys) is related to MGS. The cells of the mesoderm must divide, migrate, associate, and specialize in a precise manner to form these body parts. Any problem in any step of the process can lead to multiple abnormalities in various organ systems.

Since MGS causes severe birth defects and death in the newborn period, it can be devastating for families. Extensive examination and autopsy is often needed to confirm a diagnosis of MGS, delaying the family's answers regarding their child's death. Most parents do not know they are at risk until they have a child with MGS. This can cause feelings of anger, disbelief, and guilt.

Genetic profile

The autosomal recessive inheritance pattern in MGS is well-documented. MGS affects males and females equally. Parents of affected children are assumed to be carriers and have a 25% chance of MGS recurrence in each pregnancy. A healthy brother or sister of an affected child has a two-thirds chance of being an MGS carrier.

Research involving families in Finland (where MGS is more common) led to the first MGS gene being mapped (localized) to the short arm of chromosome 17. This means that the gene location has been narrowed down to a small potential area, but the exact location and precise details about the gene are still unknown. Non-Finnish families did not show evidence of a causative gene linked to chromosome 17. This led to the search for a second MGS gene. Studies of Northern African and Middle Eastern families resulted in the second MGS gene being mapped to the short arm of chromosome 11. More research is being performed to learn more about the precise location of both MGS genes, gene changes that cause MGS, and the role of the genes in early development.


MGS has an estimated incidence between one in 13,000 births and one in 140,000 births. This means that between one person per 50 and one person per 180 is an MGS carrier. The incidence varies among ethnic groups. Several ethnic populations have an increased incidence of MGS. The incidence in Finland is one in 9,000 births (one person in 50 is a carrier). The incidence is also higher among Belgians and Bedouins in Kuwait with one affected birth in 3,500 (one person in 30 is a carrier). The highest incidence is reported in the Gujarati Indians with one affected birth per 1,300 (one person in 18 is a carrier). The incidence among Jews in Israel is one in 50,000 (one person in 112 is a carrier). Cases of MGS have been reported in North America, Europe, Israel, Indonesia, India, Kuwait, and Japan.

Signs and symptoms

The three hallmark features of MGS are encephalocele , polycystic kidneys, and polydactyly . Approximately 90% of infants with MGS have an encephalocele. This is an opening in the skull that allows brain tissue to grow outside of the skull. Virtually 100% of infants with MGS have enlarged kidneys with cysts. Polydactyly (extra fingers and/or toes) is present in about 80% of affected children. The polydactyly is usually postaxial (the extra fingers/toes are on the same side of the hand/foot as the smallest finger/toe). In MGS, the polydactyly usually affects both the hands and feet. There may also be webbing of the fingers and toes—the skin between the fingers or toes fails to separate—leaving the digits attached to each other.

Internal examination of babies with MGS also revealed that virtually 100% have liver abnormalities. This can include halted development of the bile ducts, extra bile ducts, enlarged bile ducts, and loss of blood vessels. The liver is also usually enlarged. These liver changes are now considered by most to be another hallmark feature of MGS.

Babies with MGS often have similar facial features. Some reported features are eyes that are closer together or farther apart than usual, broad and flat nose, broad cheeks, and a wide mouth with full lips. Other features are commonly seen in MGS and are thought to be caused by a low amount of amniotic fluid surrounding the baby before birth. These features are sloping forehead, small jaw, low-set ears, and short, webbed neck. Low fluid prior to birth also frequently causes clubfoot in the newborn.

Other common features of MGS are abnormalities of the genitalia and cleft palate. The external (visible) genitalia are often small or ambiguous (not clearly male or female). There have also been reports of babies with MGS having both male and female reproductive parts (hermaphrodite). Cleft palate is seen in about 45% of babies with MGS. Cleft lip is less common but has been reported.

The symptoms of MGS are variable. Not all infants with MGS show the same signs and the characteristic signs range in severity. Some features have been described in some babies with MGS but are not as common. These include heart defects, enlarged spleen, extra spleen, hydrocephaly (extra water in the brain), absence or underdevelopment of other brain structures, and arm and leg bones that are shortened, thickened, and bowed.


Some of the features of MGS can be detected on prenatal ultrasound early in the second trimester. At that time, an encephalocele can often be seen as well as other brain abnormalities. Enlarged kidneys can also be detected at this time. As the pregnancy continues, a low amount of amniotic fluid becomes apparent. Enlarged kidneys make the abdomen appear and measure larger than usual. Cysts will make the kidneys appear bright or white on an ultrasound instead of the usual gray color.

Measurement of the alpha-fetoprotein (AFP) level from either maternal blood or amniotic fluid may help to detect an encephalocele (although most encephaloceles are closed and do not elevate AFP levels). AFP can be measured in amniotic fluid after about 12 weeks of pregnancy and in maternal blood after about 15 weeks of pregnancy. AFP elevation in either test increases the chance of an encephalocele or other abnormality in the baby's skull or spine.

When signs of MGS are seen on prenatal ultrasound in the absence of a family history, MGS is often suspected but not confirmed until after birth and autopsy. A chromosome test can be performed before birth to rule out chromosome abnormalities such as trisomy 13 . However, autopsy is usually needed to distinguish MGS from other syndromes with similar features. Every organ system of the baby is carefully examined for abnormal development.

Families at risk for recurrence of MGS can combine early ultrasound with either maternal blood AFP or amniotic fluid AFP for early detection. If early ultra-sound reveals no signs of MGS, later scans are still recommended because of the variability in expression and severity. No routine genetic tests are currently available to these families.

Treatment and management

There is no effective treatment or cure for MGS. Babies with MGS have extensive birth defects that require many surgeries to repair. Encephaloceles can be repaired by surgery after birth. Surgeries are most successful for infants with small skull abnormalities. Encephaloceles put infants at high risk for infection. The abnormalities seen in the kidneys and liver often leave the organs nonfunctional. There is often no way to repair the organs other than transplant. Even if all of these problems could be solved, infants with MGS often have underdeveloped lungs that cannot support life after birth. The lungs are underdeveloped because of the low amount of amniotic fluid prior to birth. Due to the extensive birth defects, the extensive surgeries needed to correct them, and the poor prognosis, babies born with MGS are given minimum care for comfort and warmth.

When MGS is suspected in an unborn baby, parents should be given information about the range of symptoms of MGS and the poor prognosis. Parents should also be cautioned that a diagnosis of MGS often cannot be confirmed until after birth. Prognosis can vary if the baby has atypical signs of MGS or if the baby has a different syndrome. Elective termination of affected pregnancies may be an option for some couples.


The prognosis for MGS is quite poor. Many infants with MGS are stillborn. Those that are born living usually die shortly after birth in the first hours, days, or weeks of life. Death is usually due to inability to breathe (underdeveloped lungs), infection (opening in the skull), or organ failure (decreased function of kidneys and liver). MGS is variable and there have been a couple reports of infants with milder symptoms living longer. One infant with MGS lived until four months of age. Another lived to seven months of age after surgical repair of a small encephalocele. At birth he had cystic kidneys but normal kidney function. These two case reports show that longer survival is rare but possible because of the variable expression of MGS.



Salonen, R. and P. Paavola. "Meckel Syndrome." Journal of Medical Genetics 35 (1998): 497–502.


Meckel-Gruber Syndrome Foundation. <>.

Amie Stanley, MS

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