MOMO syndrome

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Disease Profile

MOMO syndrome

<1 / 1 000 000

US Estimated

Europe Estimated

Age of onset

Infancy

ICD-10

Q87.3

Inheritance

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.

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease.

Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype.

X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder.

Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

Not applicable

Other names (AKA)

Macrosomia, obesity, macrocephaly, ocular abnormalities; Macrocrania, obesity, ocular abnormalities (retinal coloboma and nystagmus)

Summary

MOMO syndrome was named for the features associated with the syndrome including macrosomia (being larger than expected from birth), obesity, macrocephaly (having a large head size) and ocular (eye) abnormalities. It has also been proposed that mental (intellectual) disability may be used as an identifying feature of the syndrome instead of macrosomia, as macrosomia has not been reported in all affected individuals. MOMO syndrome is very rare, with only about a dozen reported cases in the scientific literature.^[1]

The exact cause of MOMO syndrome is unknown. One report has identified that the LINC00237 gene may be the cause of MOMO syndrome.^[2] Both autosomal dominant and autosomal recessive inheritance patterns have been suggested. MOMO syndrome is diagnosed when a doctor observes signs consistent with the syndrome. Tests may be completed to rule out other genetic syndromes. Treatment for the syndrome depends on the exact features that each person has.

Symptoms

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]

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms	Other Names	Learn More: HPO ID
100% of people have these symptoms
Obesity	Having too much body fat	0001513
30%-79% of people have these symptoms
Abnormal bone ossification		0011849
Bilateral microphthalmos	Abnormally small eyeball on both sides	0007633
Brachycephaly	Short and broad skull	0000248
Broad forehead	Increased width of the forehead Wide forehead [ more ]	0000337
Chorioretinal coloboma	Birth defect that causes a hole in the innermost layer at the back of the eye	0000567
Cutis marmorata		0000965
Delayed eruption of teeth	Delayed eruption Delayed teeth eruption Delayed tooth eruption Eruption, delayed Late eruption of teeth Late tooth eruption [ more ]	0000684
Dental malocclusion	Bad bite Malalignment of upper and lower dental arches Misalignment of upper and lower dental arches [ more ]	0000689
Downslanted palpebral fissures	Downward slanting of the opening between the eyelids	0000494
Epicanthus	Eye folds Prominent eye folds [ more ]	0000286
Eyelid coloboma	Cleft eyelid Notched eyelid [ more ]	0000625
Femoral bowing	Bowed thighbone	0002980
Frontal bossing		0002007
Glaucoma		0000501
High forehead		0000348
High palate	Elevated palate Increased palatal height [ more ]	0000218
Hyperconvex nail	Increased nail curvature Nail overcurvature [ more ]	0001795
Hypertelorism	Wide-set eyes Widely spaced eyes [ more ]	0000316
Intellectual disability	Mental deficiency Mental retardation Mental retardation, nonspecific Mental-retardation [ more ]	0001249
Large for gestational age	Birth weight > 90th percentile Birthweight > 90th percentile [ more ]	0001520
Large hands	large hand	0001176
Long foot	Disproportionately large feet large feet long feet [ more ]	0001833
Long philtrum		0000343
Macrocephaly	Increased size of skull Large head Large head circumference [ more ]	0000256
Nystagmus	Involuntary, rapid, rhythmic eye movements	0000639
Overgrowth	General overgrowth	0001548
Seizure		0001250
Short neck	Decreased length of neck	0000470
Short stature	Decreased body height Small stature [ more ]	0004322
Short sternum		0000879
Smooth philtrum		0000319
Sound sensitivity		0025112
Strabismus	Cross-eyed Squint Squint eyes [ more ]	0000486
Taurodontia		0000679
Thick lower lip vermilion	Increased volume of lower lip Plump lower lip Prominent lower lip [ more ]	0000179
Thick upper lip vermilion	Full upper lip Increased volume of upper lip Plump upper lip Prominent upper lip Thick upper lip [ more ]	0000215
Underfolded helix		0008577
Wide nasal base	Broad base of nose Broad nasal base Increased width of base of nose Increased width of nasal base Wide base of nose [ more ]	0012810
5%-29% of people have these symptoms
Autism		0000717
Blindness		0000618
Congenital pseudoarthrosis of the clavicle		0006585
Percent of people who have these symptoms is not available through HPO
Autosomal dominant inheritance		0000006
Delayed skeletal maturation	Delayed bone maturation Delayed skeletal development [ more ]	0002750
Retinal coloboma	Hole in the back of the eye	0000480
Wide nasal bridge	Broad nasal bridge Broad nasal root Broadened nasal bridge Increased breadth of bridge of nose Increased breadth of nasal bridge Increased width of bridge of nose Increased width of nasal bridge Nasal bridge broad Wide bridge of nose Widened nasal bridge [ more ]	0000431

Do you have updated information on this disease? We want to hear from you.

Diagnosis

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.

Treatment

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]

Organizations

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Organizations Providing General Support

American Association on Intellectual and Developmental Disabilities
501 3rd Street NW
Suite 200
Washington, DC 20001
Toll-free: (800) 424-3688
Telephone: (202) 387-1968
Fax: (202) 387-2193
Website: https://www.aaidd.org
The Society for Developmental and Behavioral Pediatrics
6728 Old McLean Village Drive
McLean, VA 22101
Telephone: 703-556-9222
E-mail: info@sdbp.org
Website: https://www.sdbp.org/index.cfm

Learn more

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

In-Depth Information

The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine.
Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
PubMed is a searchable database of medical literature and lists journal articles that discuss MOMO syndrome. Click on the link to view a sample search on this topic.

References

Di Donato N. et al. Macrocephaly, obesity, mental (intellectual) disability, and ocular abnormalities: Alternative definition and further delineation of MOMO syndrome. Am J Med Genet A. November 2012; 158A(11):2857-2862. https://www.ncbi.nlm.nih.gov/pubmed/22821547.
Vu PY, Toutain J, Cappellen D, Delrue MA, Daoud H, El Moneim AA, Barat P, Montaubin O, Bonnet F, Dai ZQ, Philippe C, Tran CT, Rooryck C, Arveiler B, Saura R, Briault S, Lacombe D, and Taine L. A homozygous balanced reciprocal translocation suggests LINC00237 as a candidate gene for MOMO (macrosomia, obesity, macrocephaly, and ocular abnormalities) syndrome. American Journal of Medical Genetics Part A. November 2012; 158A(11):2849-2856. https://www.ncbi.nlm.nih.gov/pubmed/23034868.

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Infancy

Q87.3

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease.

Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype.

X-linked dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

X-linked recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder.

Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

Not applicable

Other names (AKA)

Categories

Summary

Symptoms

Diagnosis

Treatment

Organizations

Organizations Providing General Support

Learn more

In-Depth Information

References

X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder.