Meckel syndrome

Medical quality assurance by Dr. Albrecht Nonnenmacher, MD at January 4, 2017
StartDiseasesMeckel syndrome

Meckel syndrome, also known as Meckel-Gruber syndrome, is a rare and fatal genetic condition. Meckel syndrome causes widespread symptoms that affect the central nervous system, lungs, heart, kidneys, and bones in particular. Most infants born with the condition die shortly after birth. Meckel syndrome may also be known as Meckel-Gruber syndrome or dysencephalia splanchnocystica.


Definition & Facts

Meckel syndrome is an inherited genetic disorder associated with at least eight genes. The disease most commonly causes enlarged cyst-filled kidneys, a protrusion of the brain called occipital encephalocele, and extra toes and fingers. People with Meckel syndrome may also develop other symptoms such as congenital heart defects, abnormalities, and improper bone development.

This condition is considered a Finnish heritage disease with an incidence rate that is much higher in Finland where it affects up to 1 per 9,000, although several other ethnic groups also have high incidence rates. It's believed that Meckel syndrome accounts for about 5 percent of all neural tube defects in Finland. First reported in 1822 by Johann Friedrich Meckel, early reports of the condition were also published by Georg B. Gruber.

Symptoms & Complaints

Meckel syndrome causes very severe symptoms that affect several areas of the body. The most common symptoms of the disease are enlarged kidneys with fluid-filled cysts; occipital encephalocele (a neural tube defect that involves defects in the central nervous system and a protrusion of the brain through an opening in the skull); and polydactyly, or extra fingers and toes.

Dysplastic kidneys in which very small cysts develop in the kidneys and cause them to enlarge up to 20 times their healthy size are found in about 95% of cases of Meckel syndrome. These are the three classic symptoms of Meckel, but additional symptoms are also common.

Most people with Meckel-Gruber syndrome also have fibrosis or scar tissue in the liver as well as numerous central nervous system abnormalities. These include birth defects called neural tube defects that happen when the neural tube, a layer of cells that becomes the spinal cord and brain, does not close completely during early development. Common CNS malformations associated with the disease include the Arnold-Chiari malformation of the skull and the Dandy-Walker malformation of the cerebellum.

Meckel syndrome may also lead to developmental problems with the facial features, bones, urinary system, genitalia, and the heart. Infants with the condition often have oral clefting and other facial deformities. Meckel syndrome is usually fatal before birth with fetuses often dying due to a lack of amniotic fluid or incomplete lung development. Most infants born with Meckel syndrome die soon after birth. Most Meckel syndrome fatalities are caused by pulmonary hypoplasia, (incomplete lung development) or kidney failure.


Meckel-Gruber syndrome is associated with a mutation in at least one of eight genes which account for about 75 percent of cases. The other quarter of Meckel syndrome cases are caused by other mutations that have not been discovered.

To inherit Meckel syndrome, a child must inherit a defective copy of the gene from both parents. If both parents are genetic carriers of Meckel syndrome, there is a 25 percent chance they will have a child with the condition and a 50 percent chance a child will inherit one copy of the defective gene. If a child inherits a single defective copy, they will be a carrier of Meckel syndrome but not have the condition.

The incidence rate of the condition varies from 1 in 13,250 to 1 in 140,000 births, although some ethnic groups are at a higher risk. Researchers have found that people of Belgian descent have an incidence of 1 in 3,000 while those of Finnish descent have an incidence rate of 1 in 9,000. Other high incidence rates have been found in other groups, including the Beduoins of Kuwait and Gujarati Indians. Among groups with high carrier rates, up to 1 in 18 people are carriers of Meckel syndrome. 

Diagnosis & Tests

The presence of dysplastic kidneys or enlarged kidneys due to cysts is considered an important diagnostic hallmark of the disease as it's found in about 95 percent of cases. Occipital encephalocele is found in 60-80 percent of cases of Meckel syndrome while polydactyly is found in 55-75 percent of cases. The presence of at least two of these three hallmark symptoms can make a diagnosis solid.

The level of amniotic fluid during pregnancy can also be an indicator of Meckel syndrome as amniotic levels may be severely altered. Despite this, normal amniotic fluid levels can't be considered a criteria for exclusion of Meckel syndrome as amniotic fluid levels may also remain normal.

Many symptoms can be detected by ultrasound early in the pregnancy. In most cases, a diagnosis of Meckel-Gruber syndrome is made via ultrasound during pregnancy or at birth through a clinical evaluation. Molecular genetic testing can be used to confirm a diagnosis or help with genetic counseling prior to birth. 

Treatment & Therapy

There is no treatment available for Meckel syndrome as it has a fatal outcome within days or weeks of birth due to poor lung development and renal failure. Treatment for Meckel syndrome is supportive and designed to ease pain. Genetic counseling, however, may benefit affected families.

Individuals who have a family history of Meckel syndrome can undergo genetic testing prior to conceiving to understand the risks of having a child with the fatal disease. Prenatal diagnosis is available through ultrasound as early as 14 weeks to detect abnormalities in the brain, hands and fingers, and kidneys. A prenatal diagnosis may be done early enough to give parents options for the pregnancy. 

Prevention & Prophylaxis

There is no way to prevent Meckel syndrome as it has an autosomal recessive pattern that requires both parents carrying the mutated gene to have a child with the condition.

Carriers of Meckel syndrome generally have no signs of the condition, but genetic counseling can be used to help individuals with a family history of the disease understand their risk of passing on the mutation.

Meckel syndrome may also be diagnosed through prenatal diagnostic tests on cells obtained through amniocentesis or CVS (chorionic villus sampling) or by detecting deformities through ultrasound.