Meckel Syndrome

What Causes Meckel Syndrome?

Meckel syndrome is caused by abnormal changes in genes (mutations) that impair the development of specific cell structures. Scientists have identified mutations in several different genes that account for about three-quarters of all cases of the disorder. The genes most commonly associated with Meckel syndrome include:

• B9D1
• B9D2
• CC2D2A
• CEP290
• MKS1
• RPGRIP1L
• TCTN2
• TCTN3
• TMEM67
• TMEM107
• TMEM216
• TMEM231
• TMEM237

The gene mutations associated with Meckel syndrome affect the development of microscopic hair-like structures on the surface of cells called primary cilia. Primary cilia are vital in the function of sensory cells, and they also play a role in communication pathways between nerve cells.

Is Meckel Syndrome Hereditary?

Meckel syndrome is an inherited disorder. Most cases are inherited in an autosomal recessive pattern, meaning that a child must inherit two copies of the mutated gene, one from each parent, for the disorder to develop. The parents in these cases carry just one copy of the mutation, so they typically do not show any symptoms of Meckel syndrome themselves.

If both parents carry one of the disorder-causing mutations, they have a 25 percent chance of having a child affected by the disorder with each pregnancy. In 50 percent of their pregnancies, the child will carry the mutation but not develop the condition. In 25 percent of pregnancies, their child will not carry the mutation and will not pass the disorder-causing mutation to their children.

How Is Meckel Syndrome Detected?

Meckel syndrome is most often detected during prenatal ultrasound exams. The brain malformation characteristic of the disorder may be visible early in the first trimester of pregnancy. Cysts on the kidneys may also be visible during an ultrasound exam.

Other prenatal tests, including chorionic villus sampling (CVS) or amniocentesis, can look for the disorder-causing gene mutations and confirm the diagnosis before birth.

How Is Meckel Syndrome Diagnosed?

The most common way to diagnose Meckel syndrome is via an ultrasound imaging examination during pregnancy. The malformations characteristic of the disorder, such as encephalocele, polydactyly, and kidney cysts, may be visible on ultrasound as early as 14 weeks into the pregnancy.

Chorionic villus sampling (CVS) or amniocentesis, tests performed during pregnancy, can confirm the diagnosis.

In cases where the disorder is not identified before birth, the distinctive features of Meckel syndrome typically make diagnosis possible at birth. Testing to rule out other conditions, such as trisomy 13 or Smith Lemli-Opitz syndrome, may be conducted.

PLEASE CONSULT A PHYSICIAN FOR MORE INFORMATION.

How Is Meckel Syndrome Treated?

Meckel syndrome has no cure, and the problems caused by the disorder are typically fatal either before or shortly after birth. When treatment is possible, its goal is to moderate the disorder’s symptoms and minimize the baby’s discomfort.

How Does Meckel Syndrome Progress?

Meckel syndrome is often fatal for the baby during pregnancy, and babies born with the disorder rarely survive for more than a few days after birth. The most common causes of death are respiratory or kidney failure.

How Is Meckel Syndrome Prevented?

There is no known way to prevent Meckel syndrome. Parents with a family history of the disorder or who have had another child with Meckel syndrome are advised to consult a genetic counselor to assess their risk if they plan to have another child.

Meckel Syndrome Caregiver Tips

• Take time to process your grief after a diagnosis of Meckel syndrome. Everyone grieves in their own way, and you shouldn’t hold yourself to anyone else’s standards or schedules. Acknowledge the pain you feel, and don’t be afraid to seek help when you need it.
• Find a community. Online support groups can be a valuable source of information and emotional assistance.

Meckel Syndrome Brain Science

Meckel syndrome is one of a group of disorders called ciliopathies. These disorders affect the development and function of tiny finger-like projections on the surface of cells called cilia. Cilia play a vital role in communication between cells, and they are especially important in the development and function of the liver, kidneys, eyes, and brain. When problems with cilia function occur early in fetal development, as they do in Meckel syndrome, the development of these organs can be impaired.

Meckel syndrome seems to occur when gene mutations interfere with the production of proteins crucial in cilia development. Most of the genes associated with Meckel syndrome are also associated with Joubert syndrome, so some scientists believe that Meckel syndrome is an especially severe form of Joubert syndrome.

Meckel Syndrome Research

Title:  UAB HRFD Core Center: Core A: The Hepato/Renal Fibrocystic Diseases Translational Resource

Stage: Recruiting

Principal Investigator: Lisa Guay-Woodford, MD

Children’s National Health System

Washington, DC

In 2005, The University of Alabama at Birmingham established an NIDDK-funded, interdisciplinary center of excellence in PKD-related research, emphasizing recessive PKD. In the previous Core Center award period, we developed a Core Resource to capture clinical and mutational data for ARPKD patients (“Core A: ARPKD Clinical and Genetic Resource,” NCT00575705). However, studies in the last several years have demonstrated that ARPKD and other single-gene disorders characterized by renal cystic disease and extra-renal phenotypes share numerous pathogenic features. In the current competitively- renewed Center, we have expanded this Core resource to include other hepato/renal fibrocystic diseases.

Goals for the Core A: The Hepato/Renal Fibrocystic Diseases Translational Resource are:

Clinical Database: Expand our comprehensive Clinical Database to include information from all patients who meet the inclusion criteria for hepato/renal fibrocystic diseases.

Mutational Database: Test children with ARPKD and other hepato/renal fibrocystic disease to identify genetic mutations, establish a DNA bank for patients with hepato/renal fibrocystic diseases, and develop a Mutational Database. This Database will be capable of linking clinical and mutational information via a unique identifier in a searchable format to facilitate genetic research (e.g., genotype-phenotype correlations, new disease gene studies, and modifier gene studies), translational studies, and clinical trials.

Tissue Resource: Much of the research that is performed on diseases of the kidney, including recessive genetic diseases, requires human tissue from both affected as well as non-affected (controls) individuals. In this Core Resource, researchers are establishing an independent tissue resource that would supply investigators throughout North America with samples of hepato/renal fibrocystic disease-affected tissues for studies of these disorders.

Educational Resource: Expand our multi-media, web-based resource to provide a reliable, up-to-date, and comprehensive informational resource for ARPKD and Hepato/Renal Diseases families, their physicians, and genetic counselors.

All the information regarding participation in “Core A: The Hepato/Renal Fibrocystic Diseases Translational Resource” is available at: http://www.arpkdstudies.uab.edu/.

Title: Functional Studies of Novel Genes Mutated in Primary Ciliary Dyskinesia II: Genotype to Phenotype

Stage: Recruiting

Principal investigator:  Lawrence Ostrowski, PhD

University of North Carolina Chapel Hill

Chapel Hill, NC

The purpose of this study is to measure mucociliary clearance (MCC) in groups of subjects with the disease Primary Ciliary Dyskinesia (PCD) caused by mutations in different genes. Some of these genes are associated with a milder clinical phenotype. This study seeks to determine if the milder phenotype results from mutations in a set of specific genes. The hypothesis is that subjects with PCD caused by mutations in the milder group will maintain a low but significant rate of mucociliary clearance. In contrast, patients with mutations in genes in the more severe group will have a complete absence of mucociliary clearance. These studies will help inform future treatment strategies.

Participants will undergo screening with a basic physical exam and lung function testing at the start of the study. Participants will then inhale a radiolabeled substance and undergo medical imaging to measure the clearance of mucus in the airways. Albuterol will be administered after the first imaging is completed. Lung function testing will be repeated. Finally, medical imaging will be repeated two more times to further look at clearance of mucus in the lungs. The study will be completed in one day and will last about 6 hours.