Meckel-Gruber Syndrome- Causes, Symptoms, and Diagnosis

What Is Meckel-Gruber Syndrome?

A mutation in ciliary genes is called ciliopathies. Meckel-Gruber syndrome is the result of gene mutation in structural and functional components of the cilium, and it represents the most chronic condition in the group of ciliopathies caused by cilia and flagella. Meckel-Gruber syndrome is a triad of conditions: occipital encephalopathy, postaxial polydactyly, and large polycystic kidneys.

Moreover, people with Meckel-Grubel syndrome are also found with many abnormalities related to the neural tube. These defects occur due to developmental defects during the embryonic phase of organ development, where a neural tube that usually develops as a layer of cells in the brain and spinal cord misses the mark of development during the embryonic cycle.

Additionally, Meckel-Gruber syndrome also acts as a developmental defect stimulator for bones, heart, urinary system, and facial features, and because of its chronic development, it affects one in 140,000 people around the world.

What Are the Causes of Meckel-Gruber Syndrome?

There are etiological factors affecting this syndrome, such as:

• The human body is made of cells, and each cell has genetic material known as DNA (deoxyribonucleic acid) at the center of the cell, called the nucleus. There are 23 pairs of chromosomes that are packed with this DNA that have separate functions in cells. These functions include the instructor making proteins that help in structural and functional processes and regulation of the body’s tissues and organs, turning on and off the other genes in the body, and production of RNA(Ribonucleic acid) that are needed for chemical reactions in the body.

• Meckel-Gruber syndrome is the result of 13 different gene mutations in the body. It is suspected that protein produced from genes plays an essential role in this condition. Also, the finger-like projection that carries and transmits signals between the cells at the surface plays the second most important role in this condition. Mutation of the genes affects the protein and structure, and function of cilia, which disrupts the chemical signal transmission during the developmental stage of the embryo.

• Meckel-Gruber Syndrome is a hereditary condition that is affected by a genetic disorder. This type of disorder is mostly seen in infants with the same abnormal genes they inherited from each parent.

• On the contrary, if the infant has one normal and one abnormal gene, he can only be a carrier of the disorder without showing any signs or symptoms. Moreover, marriages where both individuals are close relatives, carry more chances of passing altered genes and giving birth to a child with a genetic disorder than parents who are not related by blood but carry altered genes.

What Are the Signs and Symptoms of Meckel-Gruber Syndrome?

There are multiple signs and symptoms related to this syndrome, such as:

1. Central Nervous System or Craniofacial:

• Encephalocele: It is the condition where a child is born with a gap between two plates of the skull.
• Microcephaly: Microcephaly is an abnormality seen in children who are born with comparatively smaller-sized heads due to abnormal brain development.
• Cleft Lip: Cleft lip is a condition that occurs due to various reasons, where the tissues of the upper lip are not fused together in the normal way.
• Cleft Palate: During embryonic development, when the roof of the mouth has an abnormal opening or splitting, it is called a cleft palate.
• Microphthalmia: Microphthalmia is a chromosomal abnormality that shows abnormally smaller one or both eyes in children.
• Cerebral Vermis Agenesis: It is a condition where a child is born with a complete or partial part of the vermis (part of the brain) that helps in the voluntary control of the body and limbs.
• Micrognathia: Micrognathia is a chromosomal abnormality seen in children where the lower jaw size is relatively smaller.

2. Cardiac and Vascular Malformations:

• Multicystic Kidney Dysplasia: It is a developmental abnormality of the formation of kidneys at the time of embryonic development. There are multiple cysts found in the kidneys.

3. Musculoskeletal:

• Postaxial Polydactyly (PAP): It is a very common congenital defect where the child is born with an extra fifth digit on the feet or hands.
• Short Neck: This syndrome shows distinctive features related to an abnormality of the bones, such as a short neck.
• Clinodactyly: It is a congenital defect affecting smaller bones, such as the little finger, that causes the bone to curve to one side.
• Talipes Equinovarus: It is a developmental defect also known as clubfoot, where the foot and ankle are developed pointing down and inwards.
• Sloping Forehead: It is another structural abnormality related to this syndrome.

4. Congenital or Developmental Abnormality:

• Cryptorchidism: It is a genetic disorder seen in males, where the testicles are not moved into their proper position.
• Anencephaly: It is a fatal neural tube defect where a child is born with missing parts of the brain and skull.
• Coloboma: It is a genetic disorder where a child is missing a piece of tissue that helps in the formation of normal eyes.

5. Birth Defects:

• Oligohydramnios: Due to membrane rupture during the third trimester, the growth of the baby might be hampered, and the child might be born with a squeezed umbilical cord with difficulties during birth.

How to Diagnose Meckel-Gruber Syndrome?

The first step for a successful diagnosis is a detailed medical history, including details about the family. The syndrome is often diagnosed during the regular ultrasound checkup during pregnancy. This type of abnormality can be easily diagnosed with ultrasound at the 14th week of pregnancy. Usually, doctors go for genetic testing to confirm the disease. Moreover, if required, the doctor can suggest a chromosomal analysis to rule out other disorders.

What Are the Complications Associated With Meckel-Gruber Syndrome?

There are the following health-related complications associated with this syndrome:

• Polycystic Dysplastic Kidneys: It is a developmental abnormality of one or both kidneys in the womb.

• Polydactyly: It is a condition where a child is born with five fingers or five toes.

• Occipital Encephalocele: It is a condition where the occipital bone of the skull has an abnormal size.

• Fibrotic Cystic Changes in the Liver: It is a condition caused by a mucous blockage in the liver.

• Absence of Olfactory Lobes: Absence of olfactory lobes causes loss of smell.

• Anencephaly: It is a condition where the baby is born without some of the brain structure.

• Hydrocephalus: It is a condition where the brain cavity is filled with fluid, causing pressure on the brain.

• Orofacial Clefts: The child with this condition has a cleft lip and cleft palate.

• Atrial Septal Defect: It is a birth defect where a child is born with a hole in the wall of the heart.

How to Treat Meckel-Gruber Syndrome?

There are no successful treatments available due to the life-threatening condition and multi-organ involvement of this syndrome. It is very rare for a child with this severe syndrome to even reach an operation theatre. The doctor usually suggests genetic counselling for the parents before conceiving.

Conclusion:

Meckel-Gruber syndrome is a very critical condition caused by a genetic mutation in children. The symptoms of the condition are fatal, and there are no curative treatment options available for it. If the parents are aware of the possibilities of genes they might be carrying, they should immediately go to the doctor for advice related to pregnancy. Owing to the severity of the condition, lack of awareness, and no treatment option, this syndrome carries high rates of death.