Meckel-Gruber syndrome is a rare, inherited disorder. A baby born with it will typically only survive a few days due to the severity of health issues that the condition causes.

Johann Friedrich Meckel first recorded Meckel-Gruber syndrome in 1822. Later in 1934, G. B. Gruber published reports on several babies born with the condition. He named the condition dysencephalia splanchnocystica.

Since then, researchers have renamed the disorder Meckel-Gruber syndrome to recognize their discoveries.

Meckel-Gruber syndrome is a rare genetic condition. It is passed down to a child in utero when both parents have the recessive gene alteration. But in some cases, the cause is unknown.

Meckel-Gruber syndrome is a severe condition that typically results in the baby living for no more than a few days to a few weeks.

In this article, we will discuss Meckel-Gruber syndrome, including its causes, symptoms, and more.

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Meckel-Gruber syndrome is a rare genetic disorder that causes abnormalities in multiple organs. The three characteristic features are:

  • protrusion of a portion of the brain and surrounding membranes (meninges) through a defect in the back of the skull
  • multiple cysts on the kidneys
  • extra fingers and/or toes (polydactyly)

Babies born with the condition often have issues that affect several organs and systems, including:

  • face and head
  • heart
  • lungs
  • liver
  • genitourinary tract

Worldwide, the condition occurs in 1 in 13,250 to 1 in 140,000 live births. Some populations have a higher likelihood of occurrence. The groups with the highest rates tend to either have a limited genetic pool or feature relationships between blood relatives. Medical literature has reported more than 200 cases.

Some groups with higher prevalence include populations of:

  • Finnish descent: 1 in 9,000
  • Belgian descent: 1 in 3,000
  • Gujarati Indians: 1 in 1,300

Genetic changes are the primary cause of Meckel-Gruber syndrome. Experts note that alterations in 13 different genes are responsible for its development in 75% of cases. These genes are:

  • B9D1
  • CC2D2A
  • MKS1
  • B9D2
  • CEP290
  • TCTN2
  • TMEM107
  • TCTN3
  • TMEM237
  • TMEM67
  • TMEM216
  • TMEM231

In the remaining 25% of cases, the genetic cause is unknown.

The majority of these genes can also cause another condition known as Joubert syndrome. Some doctors believe that Meckel-Gruber syndrome may be a particularly severe form of Joubert syndrome.

Experts also note that many of the genes responsible for Meckel-Gruber syndrome produce proteins that influence cellular function and development through projections on cells known as primary cilia. Cilia act as receivers and pass on information that cells need to develop and function.

Several important structures, including the brain, heart, kidneys, eyes, and liver, use cilia during development and to help them function.

When alterations occur in the above genes, they do not produce the correct proteins, which causes cilia to not function properly. This can lead to a variety of developmental problems.

Meckel-Gruber syndrome is an autosomal recessive disease. This means that for a fetus to acquire the disorder, it would need to receive a copy of a variant gene from each parent.

The condition has an equal chance of occurring in males and females. When two parents have the recessive gene, a baby has a 25% chance of inheriting the disorder. The odds of occurrence do not increase or decrease with additional children.

Meckel-Gruber syndrome can affect multiple areas of the body. Often, affected areas do not form completely and may have obvious symptoms. Babies born with the condition can vary greatly in the symptoms they present. Typical symptoms include:

  • Occipital encephalocele: A condition where the skull does not fully form, leaving a gap at the back. Often, the brain and membranes covering it protrude. The skull may fill with excessive cerebrospinal fluid, putting pressure on the brain.
  • Other central nervous system problems: Some other problems with the central nervous system may include the absence of parts of the brain, scalp, or skull. A baby may also have microcephaly, a condition where the circumference of the head is too small.
  • Distinct facial features: A baby may have a small jaw, low-set ears, cleft palate or lip, short neck, or sloping forehead.
  • Issues with the eyes: The eyes may appear smaller than normal and lack or have underdeveloped nerves connecting to them.
  • Multiple cysts on the kidneys: The most common feature of the syndrome are fluid-filled cysts that replace healthy kidney tissue. The cysts can vary in size and often grow over time. They can also cause poor kidney function and kidney failure.
  • Finger and toe problems: A baby may have extra fingers or toes, often present on the outer edge of the small outer finger (pinky). They may develop a clubbed foot, webbing between the fingers or toes, and bowing of elongated arms and legs.
  • Genitourinary tract problems: These can include issues with the testes and bladder formation and incomplete development of the genitalia.
  • Other affected organs: Meckel-Gruber syndrome can affect the liver, heart, lungs, and other organs in the body. This can lead to several problems with the function of these organs.

Often, issues that affect the central nervous system, kidneys, or lungs cause perinatal death resulting in stillbirth.

Diagnosis can occur prior to birth. A doctor may be able to identify features through a routine ultrasound. Often a doctor can see any problems on an ultrasound starting around week 14.

If they suspect Meckel-Gruber syndrome, they will likely recommend genetic testing. A chromosomal analysis may help rule out trisomy 13, which mimics Meckel-Gruber syndrome. Biochemical testing can help rule out Smith-Lemli-Opitz syndrome.

If prenatal testing indicates Meckel-Gruber syndrome, the parents may choose to terminate the pregnancy. Genetic counselors and other healthcare staff may be able to help guide a family toward the correct decision for them.

At present, treatment cannot cure or correct Meckel-Gruber syndrome. The condition is always fatal, with only 2 reported cases where the child lived past infancy. As such, treatment is typically supportive and addresses symptoms.

Parents may find counseling services and other mental-health support helpful. Most hospitals have mental-health support staff, counselors, and case managers to help families find the support they need.

The outlook is poor for babies born with Meckel-Gruber syndrome. Problems in the brain, lungs, and kidneys lead to death in 100% of cases.

The typical life expectancy is measured in days or weeks, though a few children have lived past infancy. When the condition affects the lungs, kidneys, or central nervous system, it often results in perinatal demise.

Meckel-Gruber syndrome is a rare genetic condition that a person inherits from both parents. The condition often affects multiple organs in the body and typically results in perinatal death or death within a few days of being born.

Doctors may identify problems on an ultrasound, which often prompts additional testing to confirm a diagnosis. How parents proceed is largely up to them. Some may choose to continue the pregnancy, while others may wish to terminate it.

Hospitals often have support staff who can help parents cope with stress, grief, and other emotions regarding the outlook for their baby.