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

• Craniostenosis
• CSO (Craniosynostosis)

What is Craniosynostosis? (Definition/Background Information)

• Craniosynostosis is a birth defect of the brain characterized by the premature closure of one or more of the joints between the bones of the skull (called the cranial sutures) before brain growth is complete
• The first sign is an abnormally shaped skull; other features can include signs of increased intracranial pressure, developmental delays, intellectual disability, seizures, and blindness, caused by constriction of the growing brain
• Closure of a single suture is most common and does not prevent the brain from expanding to a normal volume. When many sutures close prematurely, the skull cannot expand to accommodate the growing brain, leading to increased pressure and impaired development of the brain
• Craniosynostosis can be caused by genetic mutations, certain metabolic diseases (such as rickets or an overactive thyroid) or can be associated with other disorders such as microcephaly and hydrocephalus
• Treatment generally consists of surgery to improve the symmetry and appearance of the head and to relieve pressure on the brain and the cranial nerves

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

Who gets Craniosynostosis? (Age and Sex Distribution)

• Craniosynostosis is a congenital disorder, in many cases. The presentation of symptoms may occur at birth or during childhood
• Both males and females may be affected
• Worldwide, individuals of all racial and ethnic groups may be affected

What are the Risk Factors for Craniosynostosis? (Predisposing Factors)

• A positive family history may be an important risk factor, since Craniosynostosis can be inherited
• Craniosynostosis may be also associated with certain metabolic disorders and conditions involving the head/brain (such as hydrocephalus and small-sized head)

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 Craniosynostosis? (Etiology)

Craniosynostosis can be caused by genetic mutations, certain metabolic diseases (such as rickets or an overactive thyroid) or can be associated with other disorders such as microcephaly and hydrocephalus.

• Craniosynostosis is most often sporadic (occurs by chance). Most often it occurs as an isolated (non-syndromic) condition that has the characteristics of a multifactorial trait (a feature likely caused by the interaction of several genes with environmental factors, most of which are unknown)
• However, in some families, Craniosynostosis may be inherited. The pattern of inheritance can either be autosomal recessive or autosomal dominant 
• Craniosynostosis can also be a feature of many different genetic syndromes that have a variety of inheritance patterns and chances for recurrence, depending on the specific syndrome present
• Syndromic Craniosynostosis is present in about 15% of individuals with the condition
• It is important for the child as well as family members to be examined carefully for signs of a syndromic cause (inherited genetic disorder) of Craniosynostosis such as limb defects, ear abnormalities, or cardiovascular malformations
• Some of the more common genetic syndromes associated with Craniosynostosis include Crouzon syndrome, Apert syndrome, Pfeiffer syndrome and Saethre-Chotzen syndrome

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

Autosomal dominant: 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.

Autosomal recessive: Autosomal recessive conditions are traits or disorders that occur when two copies of an abnormal gene have been inherited on a non-sex chromosome. If both parents have an autosomal recessive condition, there is a 100% likelihood of passing on the mutated genes to their children. If, however, only one mutant copy of the gene is inherited, the individual will be a carrier of the condition, but will not be present with any symptoms. Children born to two carriers, have a 25% chance of being homozygous dominant (unaffected), a 50% chance of being heterozygous (carrier), and a 25% chance of being homozygous recessive (affected).

What are the Signs and Symptoms of Craniosynostosis?

The signs and symptoms of Craniosynostosis may include:

• Bicoronal synostosis
• Brachyturricephaly
• Carpal bone malsegmentation                   
• Cone-shaped epiphyses of the phalanges of the hand   
• Cone-shaped epiphyses of the toes
• Dolichocephaly
• Frontal bossing
• Hallux valgus
• Oxycephaly
• Scaphocephaly
• Shortening of all distal phalanges of the fingers
• Shortening of all middle phalanges of the fingers
• Trigonocephaly
• Turricephaly
• Unicoronal synostosis

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

• Brachydactyly 
• Cleft soft palate 
• Headache
• Hypermetropia 
• Hypotelorism 
• Increased number of teeth 
• Myopia
• Seizures
• Triphalangeal thumb 
• Visual field defect

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

How is Craniosynostosis Diagnosed?

Craniosynostosis 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

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 Craniosynostosis?

The complications of Craniosynostosis may include:

• Intellectual impairment
• Loss of vision
• Severe emotional stress

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

How is Craniosynostosis Treated?

Presently, there is no cure for Craniosynostosis. The treatment is usually given to manage the signs and symptoms and any complications that develop.

How can Craniosynostosis be Prevented?

• Currently, Craniosynostosis may not be preventable, since it may be caused by genetic factors
• Genetic testing of the expecting parents (and related family members) 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 Craniosynostosis? (Outcomes/Resolutions)

• The prognosis of Craniosynostosis is dependent upon the severity of the signs and symptoms and associated complications, if any
• Individuals with mild conditions have better prognosis than those with severe symptoms and complications
• Typically, the prognosis may be assessed on a case-by-case basis

Additional and Relevant Useful Information for Craniosynostosis:

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

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