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Meckel Syndrome

Last updated Nov. 13, 2018

Approved by: Maulik P. Purohit MD, MPH

Meckel Syndrome (MES) is an inherited disorder affecting the neural tube.

What are the other Names for this Condition? (Also known as/Symptoms)

  • Dysencephalia Splanchnocystica
  • Gruber Syndrome
  • MES (Meckel Syndrome)

What is Meckel Syndrome? (Definition/Background Information)

  • Meckel Syndrome (MES) is an inherited disorder affecting the neural tube. The neural tube is a group of cells in the developing embryo, which multiplies and differentiates to give rise to the brain and the spinal cord. When the neural tube does not close properly during development, a neural tube defect ensues
  • This multi-system syndrome is characterized by 3 major features, namely
    • Brain abnormalities, known as occipital encephalocele, in which brain matter protrudes through a defect in the skull
    • Kidney abnormalities including polycystic kidneys or formation of cysts on the kidneys
    • Digit abnormalities, such as polydactyly, or extra fingers and/or toes
  • Since Meckel Syndrome is an inherited disorder, having a family history of the condition is a known risk factor for being diagnosed with it
  • In approximately 75% of the reported cases, the syndrome is caused by mutation(s) in one of a set of 8 genes responsible for the formation and function of cilia
    • Cilia are microscopic finger-like projections on cell surfaces. Cilia are present on the surfaces of liver, kidney, and specialized cells in the eyes that sense light
    • Cilia play a role in signalling pathways, thereby modulating the function of many organs. The presence of cilia is necessary to the proper functioning of these organs
  • Although defects in the structure and functioning of cilia are known to cause Meckel Syndrome, the exact mechanism of development of abnormalities in organs is still under investigation. The disorder is inherited in an autosomal recessive manner
  • Apart from brain, kidney, and fingers/toes abnormalities, the symptoms of the syndrome may also include facial abnormalities, fibrosis of the liver, underdeveloped genitourinary tract, abnormal growth of bones, and problems with the central nervous system
  • Meckel Syndrome can be diagnosed prenatally, with the help of ultrasonography and other imaging methods. Molecular genetic analysis of fetal cells can confirm the syndrome, as well as rule out other similar medical conditions
  • The potential complications arising from Meckel Syndrome are many and varied, affecting multiple organs. In many cases, fetal death is noted. If a child is born with the syndrome, he/she may have breathing problems and kidney failure, both of which can be fatal
  • The treatment options available for Meckel Syndrome are limited. Treatment is often tailored toward making the newborn breathe and be comfortable. A surgical repair of the skull may be recommended
  • Since Meckel Syndrome is a genetic disorder, there is no guidance or method available to prevent it from occurring. Prospective parents may benefit from genetic testing and genetic counselling before planning for a baby
  • The prognosis of Meckel Syndrome is very poor and 100% fatalities are reported either in-utero or within a few weeks following birth of the child

Who gets Meckel Syndrome? (Age and Sex Distribution)

  • According to various studies, Meckel Syndrome affects 1 in 13,250-140,000 populations. However, certain populations have a greater incidence rate:
    • 1: 9000 in individuals with Finnish ancestry
    • 1: 3000 in those with Belgian ancestry
    • 1: 3500 in Bedouin population of Kuwait
    • 1: 1300 is Indian Gujarati community
    • 1: 50,000 in Israeli Jews
  • It is a congenital disorder and both male and female genders are equally susceptible to MES
  • The syndrome is reported to occur worldwide in people of all races and ethnic backgrounds

What are the Risk Factors for Meckel Syndrome? (Predisposing Factors)

  • Meckel Syndrome is a genetic disorder. Therefore, having a family history of the disorder is a major risk factor

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases ones chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Meckel Syndrome? (Etiology)

In about three-quarters of the reported cases, Meckel Syndrome is caused by mutations in 1 of the 8 genes involved in the formation and functioning of cilia.

  • Under normal circumstances, the genes code for proteins that are necessary for the formation and proper functioning of the cilia
    • Cilia are minute hair-like projections on cell surfaces, and are crucial for the structural integrity and functioning of the brain, liver, kidney, and bone cells
    • Cilia are present on the cells in the retina that sense light, thereby playing a role in ensuring proper vision
  • When any gene identified as important in ciliary structure and function is mutated, the result is impaired signalling within and between cells during early developmental stages of the embryo
  • The exact mechanism of how defective cilia cause structural and functional aberrations in organs is unclear, and scientific research is currently underway to understand the same
  • The disorder is inherited in an autosomal recessive manner. Although, in 25% of the affected individuals, the genetic cause of Meckel Syndrome is not clear

Autosomal recessive: Autosomal recessive conditions are traits or disorders that occur when two copies of an abnormal gene have been inherited on a non-sex chromosome. If both parents have an autosomal recessive condition, there is a 100% likelihood of passing on the mutated genes to their children. If, however, only one mutant copy of the gene is inherited, the individual will be a carrier of the condition, but will not be present with any symptoms. Children, born to two carriers, have a 25% chance of being homozygous dominant (unaffected), a 50% chance of being heterozygous (carrier), and a 25% chance of being homozygous recessive (affected). 

What are the Signs and Symptoms of Meckel Syndrome?

The most common signs and symptoms of Meckel Syndrome include: (based on the organs affected)

  • Occipital encephalocele
    • Unsealed parts in skull
    • Protrusion of brain and brain membrane (meninges) through a gap in the skull. This gap can be in the front or back of the skull
    • Inflammation of the meninges
    • Excess fluid accumulation in the skull (hydrocephaly), putting pressure on the brain tissue
    • Microcephaly, or small head
    • Anencephaly, or incomplete formation of brain
  • Kidneys
    • Cysts on the kidney; kidney enlargement because of presence of cysts
    • Progressively deteriorating kidney function
    • End-stage kidney disease
    • In pregnant women carrying a fetus with the disorder, a condition called oligohydramnios may occur. In this condition, there is a reduction in the volume of the amniotic fluid surrounding the fetus
  • Polydactyly and other abnormalities of the digits
    • Extra toes and fingers
    • Webbed fingers and toes (syndactyly)
    • Fingers (especially the 5th) in a permanently bent position (clinodactyly)
  • Bone deformities
    • Bow legs and bowed appearance of long bones in the arms
    • Clubfoot
    • Short neck
  • Facial abnormalities
    • Small jaw (micrognathia)
    • Cleft palate
    • Small eyes
    • Widely-spaced eyes (hypertelorism)
    • Sloping forehead
    • Malformed ears set low on the head
    • Malformed pupils (iris coloboma)
  • Genitourinary tract abnormalities
    • Cryptorchidism, where the one or both testes do not descend into the scrotal sacs
    • Incomplete development of the urinary bladder
    • Incomplete genitalia
  • Scar tissue formation (fibrosis) of liver and enlargement of liver
  • Enlargement of spleen
  • Scar tissue formation in the bile ducts
  • Breathing problems owing to underdeveloped lungs
  • Heart defects
    • Atrial septum malformation
    • Ventricular septum malformations
  • Patent ductus arteriosus, in which the passage between the lungs and the aorta remains open 
  • Defects in the spinal cord

How is Meckel Syndrome Diagnosed?

The diagnosis of Meckel Syndrome may be made prenatally, or after the birth of the baby. Information from the following are required to make the diagnosis:

Prenatal tests:

  • Evaluation of mother’s history of pregnancies that resulted in any stillbirths
  • Alpha-fetoprotein (AFP) test in mother’s blood after 15 weeks of pregnancy
  • AFP test of the amniotic fluid via amniocentesis (at 12-14 weeks of gestation)
  • Ultrasonography of the fetus, which may detect encephalocele, polydactyly, and polycystic kidneys (after 12 weeks of gestation)
  • Magnetic resonance imaging (MRI) of the fetus
  • Molecular genetic testing of fetal cells to detect gene mutations causing the symptoms, or to rule out other conditions with similar symptoms

Postnatal tests:

  • A complete and thorough physical examination, with assessment of the presenting symptoms
  • An evaluation of family medical history
  • Genetic testing to check for causative mutations or to rule out other medical conditions that can cause similar symptoms

Autopsy: In cases where a child dies, an autopsy can provide valuable information regarding Meckel Syndrome to the healthcare professionals and parents alike.

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Meckel Syndrome?

Meckel Syndrome can lead to the following complications:

  • Breathing difficulties leading to respiratory failure
  • Kidney dysfunction, progressive kidney malfunction and kidney failure
  • End-stage kidney disease
  • Enlarged liver (hepatomegaly)
  • Enlarged spleen (splenomegaly)
  • Heart problems owing to septal defects

Note: Any one or more of the above conditions can be fatal.

How is Meckel Syndrome Treated?

At the present time, there are no specific treatment options available for Meckel Syndrome. The treatments are geared toward addressing the symptoms. A team of specialists from various fields typically work in close cooperation to treat a newborn with the syndrome.

The treatment options may include:

  • Repair of heart valve abnormalities, if warranted
  • Repair of encephalocele, if needed
  • Supportive care to make the newborn comfortable

How can Meckel Syndrome be Prevented?

  • Currently, there are no specific methods or guidelines to prevent Meckel Syndrome, since it is a genetic condition
  • Genetic testing of the expecting parents (and related family members) and prenatal diagnosis (molecular testing of the fetus during pregnancy) may help in understanding the risks better during pregnancy
  • If there is a family history of the condition, then genetic counseling will help assess risks, before planning for a child
  • Active research is currently being performed to explore the possibilities for treatment and prevention of inherited and acquired genetic disorders such as Meckel Syndrome

Regular medical screening at periodic intervals with tests and physical examinations are highly recommended.

What is the Prognosis of Meckel Syndrome? (Outcomes/Resolutions)

  • The prognosis of Meckel Syndrome is extremely poor; the mortality rate is 100%
  • Many fetuses succumb to the disease in-utero (in the womb), while newborns survive from few days to a few weeks

Additional and Relevant Useful Information for Meckel Syndrome:

Meckel Syndrome is also known as ‘Dysencephalia Splanchnocystica’ and ‘Gruber Syndrome’.

What are some Useful Resources for Additional Information?

References and Information Sources used for the Article:

Helpful Peer-Reviewed Medical Articles:

Reviewed and Approved by a member of the DoveMed Editorial Board
First uploaded: May 21, 2016
Last updated: Nov. 13, 2018