What are the other Names for this Condition? (Also known as/Synonyms)

• Coronal Craniosynostosis Syndrome
• Muenke Non-Syndromic Coronal Craniosynostosis

What is Muenke Syndrome? (Definition/Background Information)

• Muenke Syndrome is a condition characterized by the premature closure of the coronal suture of the skull (coronal craniosynostosis) during development. This affects the shape of the head and face
• Other variable features include abnormalities of the hands or feet, hearing loss and developmental delay
• Muenke Syndrome is caused by mutations in the FGFR3 gene. It is inherited in an autosomal dominant pattern

(Source: Muenke Syndrome; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

Who gets Muenke Syndrome? (Age and Sex Distribution)

• Muenke Syndrome is a rare congenital disorder, with an estimated birth prevalence of 1:30,000
• The condition accounts for 8% of all cases of craniosynostoses
• The manifestation of symptoms may begin before birth, or become apparent shortly after birth
• Both gender may be affected by Muenke Syndrome

What are the Risk Factors for Muenke Syndrome? (Predisposing Factors)

• A positive family history may be an important risk factor, since Muenke Syndrome is an inherited condition
• Currently, no other risk factors have been clearly identified for this disorder

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Muenke Syndrome? (Etiology)

Muenke Syndrome is caused by mutations in the FGFR3 gene.

• This gene provides instructions for making a protein that is involved in the development and maintenance of bone and brain tissue
• A single mutation in the FGFR3 gene causes the FGFR3 protein to be overly active, which interferes with normal bone growth and allows the bones of the skull to fuse before they should
• Muenke Syndrome is inherited in an autosomal dominant manner

(Source: Muenke Syndrome; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

Autosomal dominant inheritance: Autosomal dominant conditions are traits or disorders that are present when only one copy of the mutation is inherited on a non-sex chromosome. In these types of conditions, the individual has one normal copy and one mutant copy of the gene. The abnormal gene dominates, masking the effects of the correctly function gene. If an individual has an autosomal dominant condition, the chance of passing the abnormal gene on to their offspring is 50%. Children, who do not inherit the abnormal gene, will not develop the condition or pass it on to their offspring.

What are the Signs and Symptoms of Muenke Syndrome?

The signs and symptoms of Muenke Syndrome may vary in type and severity among affected individuals. About 6-7% of those with causative FGFR3 mutation(s) may be asymptomatic.

The signs and symptoms of those who are symptomatic may include:

• Abnormally shaped head
• Brachydactyly
• Broad hallux
• Capitate-hamate fusion 
• Clinodactyly
• Cone-shaped epiphyses of the phalanges of the hand 
• Downslanted palpebral fissures
• High palate
• Intellectual disability
• Low anterior hairline
• Midface retrusion
• Radial deviation of finger 
• Short middle phalanx of finger
• Short middle phalanx of toe
• Thimble-shaped middle phalanges of hand

Frequently present symptoms in 30-79% of the cases:

• Brachycephaly 
• Carpal synostosis 
• Cone-shaped epiphysis
• Coronal craniosynostosis 
• High, narrow palate
• Hypertelorism
• Increased intracranial pressure
• Malar flattening
• Plagiocephaly
• Proptosis
• Ptosis
• Sensorineural hearing impairment 
• Short foot
• Short palm
• Tarsal synostosis

Occasionally present symptoms in 5-29% of the cases:

• Global developmental delay 
• Hydrocephalus 
• Hypermelanotic macule
• Hypopigmentation of hair 
• Hypopigmented skin patches 
• Macrocephaly

(Source: Muenke Syndrome; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

How is Muenke Syndrome Diagnosed?

Muenke Syndrome is diagnosed on the basis of the following information:

• Complete physical examination
• Thorough medical history evaluation
• Assessment of signs and symptoms
• Laboratory tests
• Imaging studies
• Biopsy studies, if necessary
• Molecular genetic testing to check for or confirm causative gene mutation(s)

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Muenke Syndrome?

The complications of Muenke Syndrome may include:

• Increased intracranial pressure 
• Epilepsy
• Behavioral abnormalities

Complications may occur with or without treatment, and in some cases, due to treatment also.

How is Muenke Syndrome Treated?

• There is no cure for Muenke Syndrome, since it is a genetic condition. The treatment is usually given to manage the signs and symptoms and any complication that develops
• Treatment methods for the syndrome may include surgeries to reduce the risk of complications, as well as repair of craniosynostosis
• A concerted effort by medical professionals from different disciplines, such as neurology, audiology and psychiatry, is often necessary for the management of signs and symptoms of Muenke Syndrome

How can Muenke Syndrome be Prevented?

Currently, Muenke Syndrome may not be preventable, since it is a genetic disorder.

• Genetic testing of the expecting parents (and related family members), if available, and prenatal diagnosis (molecular testing of the fetus during pregnancy) may help in understanding the risks better during pregnancy
• If there is a family history of the condition, then genetic counseling will help assess risks, before planning for a child
• Active research is currently being performed to explore the possibilities for treatment and prevention of inherited and acquired genetic disorders

Regular medical screening at periodic intervals with tests and physical examinations are recommended.

What is the Prognosis of Muenke Syndrome? (Outcomes/Resolutions)

• The prognosis of Muenke Syndrome is dependent upon the severity of the signs and symptoms and associated complications, if any
• With a timely diagnosis and prompt treatment, affected individuals may have good outcomes with a normal life expectancy
• The prognosis may be typically assessed on a case-by-case basis

Additional and Relevant Useful Information for Muenke Syndrome:

The following DoveMed website link is a useful resource for additional information:

http://www.dovemed.com/diseases-conditions/rare-disorders/