MOMO syndrome

MOMO syndrome is associated with macrosomia (being larger than expected from birth), obesity, macrocephaly (having a large head size) and ocular (eye) abnormalities. Some of the eye abnormalities may include coloboma or uncontrolled movement of the eye (nystagmus). The symptoms of MOMO syndrome begin at birth. Babies are typically larger than expected, and they may have low muscle tone (hypotonia). Children with the syndrome also typically meet milestones such as walking later than expected (developmental delay) and have intellectual disability.^[1] Other features may include seizures, bowing of the legs, and slower maturation of the bones (delayed bone age).^[1][2]

Although intellectual disability has been present in all individuals with MOMO syndrome, the severity of intellectual disability may vary. Some people have been described as having autism or detached behavior. Children with MOMO syndrome typically have speech delay, meaning they learn to talk later than other children and may not have the ability to speak as many words as other children.^[2]

People with MOMO syndrome tend to have distinctive facial features. These facial features can include having eyes that slant upward or downward, a flat nasal bridge, and a short round head (brachycephaly).^[1] 

It is not known how MOMO syndrome is inherited. It was originally thought that MOMO syndrome is inherited in an autosomal dominant manner.^[1] This means that only one copy of the gene that causes MOMO syndrome needs to be changed in order for a person to show signs of the syndrome. We inherit one copy of each gene from our mother and the other from our father.

Autosomal dominant inheritance was originally suspected because each of the reported cases of MOMO syndrome have only occurred once in a family, and the person with MOMO syndrome has been born to healthy parents.^[1] When only one person in a family is affected with a particular genetic syndrome, autosomal dominant inheritance is a possible explanation because the genetic change (mutation) in only one copy of the gene may be new (de novo) in the person who has the syndrome. Therefore, one possible explanation is that each case of MOMO syndrome that is reported occurred when a new genetic change happened by chance when each affected individual was conceived.

If MOMO syndrome is inherited in an autosomal dominant manner, it occurs by chance, and it is very unlikely for two parents who have a child with MOMO syndrome to have another child with MOMO syndrome. An individual with MOMO syndrome has not been known to have children. However, if this were to happen, each child would have a 50% chance to inherit MOMO syndrome as well.

In one case, a person with MOMO syndrome was found to have a genetic change in the LINC00237 gene. In this case, a new inheritance pattern, called autosomal recessive inheritance, was suspected. Autosomal recessive inheritance occurs when both copies of the same gene have changes that cause them not to work properly. In the individual with MOMO syndrome who had changes in the LINC00237 gene, both copies of the gene were not functioning correctly, which caused some researchers to suspect that MOMO syndrome may be inherited in an autosomal recessive manner.^[2]

If MOMO syndrome is inherited in an autosomal recessive manner, it means that both parents of an individual with the syndrome would have a genetic change in only one of the copies of the gene that causes the syndrome. This means they would be carriers of MOMO syndrome. If this were the case, when two carriers of MOMO syndrome have children together, for each child there would be a:

• 25% chance that the child will have MOMO syndrome
• 50% chance that the child will be a carrier of MOMO syndrome like the parents
• 25% chance that the child will have two working copies of the gene, so the child will not have MOMO syndrome and will not be a carrier

It is important to remember that we do not know for sure how MOMO syndrome is inherited. Therefore, the exact chance that parents who have a child with MOMO syndrome could have another affected child is uncertain. 

MOMO syndrome is suspected when a doctor observes signs and symptoms that are consistent with the syndrome. Specifically, the combination of obesity, having a large head (macrocephaly), eye abnormalities, and intellectual disability may make a doctor suspect MOMO syndrome.^[1] The doctor may recommend genetic testing to rule out other genetic syndromes with similar features. In some cases, the doctor may recommend a test called whole exome sequencing that analyzes every gene in the body. Unfortunately, because the exact genetic cause of MOMO syndrome is not known, genetic testing may be used to rule out other genetic causes of specific symptoms, but it cannot be used to diagnose a person with MOMO syndrome.

Unfortunately, there is no cure for MOMO syndrome. Treatment options are based on the specific symptoms that each person has. Options may include special education in school, therapies to help children meet developmental milestones, and meeting with a nutritionist to discuss methods to help affected individuals maintain a healthy weight. All people who are diagnosed with MOMO syndrome should be evaluated by an ophthalmologist to see if there are any eye abnormalities.^[2]

Because there have only been a few cases of MOMO syndrome reported in the medical literature, it is unclear if there are any long-term complications associated with the syndrome. It is not known if having MOMO syndrome may decrease the life expectancy in affected individuals. Obesity may be associated with other health problems that can impact a person’s life expectancy. Other potential complications may depend on the specific signs and symptoms present in each individual.^[1][2]