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Primary Craniosynostosis

NORD is very grateful to Robert F. Keating, MD, Professor and Chief, Department of Neurosurgery; President, Medical Staff, Children's National Medical Center, Washington, DC, for assistance in the preparation of this report.

Synonyms of Primary Craniosynostosis

  • craniostenosis

Disorder Subdivisions

  • nonsyndromic synostosis
  • syndromic synostosis

General Discussion

Primary craniosynostosis is a general term for the improper development of the bones of the skull, which can result in an abnormal head shape in affected individuals. Craniosynostosis refers to the premature fusion of the fibrous joints (sutures) between certain bones of the skull. The severity of primary craniosynostosis can vary from one person to another. Raised intracranial pressure is unlikely with single suture abnormalities and thus intelligence is usually unaffected. Primary craniosynostosis may occur as an isolated finding or as part of a syndrome. Patients with syndromic conditions generally have more than one suture involved. Not surprisingly, the therapeutic options and outcomes are dependent upon the degree of suture involvement. The main treatment for primary craniosynostosis is surgery, but not all affected children will require surgery. The exact cause of primary craniosynostosis is unknown, although the skull abnormalities may result from the abnormal hardening (ossification) of the cranial sutures. Primary craniosynostosis is distinguished from secondary craniosynostosis, which occurs because of a primary failure in brain growth which in turn may lead to abnormalities in head shape, occasionally mimicking craniosynostosis.

Symptoms

Primary craniosynostosis is usually apparent at birth or within a few months shortly therafter (neonatal period). Mild cases may go undiagnosed until early during childhood.

An infant's skull has seven bones and several joints called sutures. Sutures are made of tough, elastic fibrous tissue and separate the bones from one another. Sutures meet up (intersect) at two spots on the skull called fontanelles, which are better known as an infant's "soft spots". The seven bones of an infant's skull normally do not fuse together until around age two or later. The sutures normally remain flexible until this point. In infants with primary craniosynostosis, the sutures abnormally stiffen or harden causing one or more of the bones of the skull to prematurely fuse together. This in turn, may lead to asymmetric skull growth.

In primary craniosynostosis, the severity and specific shape of an infant's skull depends upon how many and which sutures and bones are affected. In most cases, only one suture is affected (simple craniosynostosis). Consequently, growth in that area of the skull is hindered, but growth (in order to accommodate the infant's expanding brain) in the unaffected areas continues. This results in an abnormal skull shape.

In most cases of primary craniosynostosis, affected children have normal intelligence and do not have other abnormalities besides the skull malformation. However, when multiple sutures are affected, the skull may be unable to expand enough to accommodate the growing brain. If left untreated, this can cause increased pressure within the skull (intracranial pressure) and can potentially result in cognitive impairment or developmental delays. Increased pressure within the skull can also cause vomiting, headaches, and decreased appetite. In some rare cases, additional symptoms can develop including seizures, misalignment of the spine, or eye abnormalities.

Craniosynostosis may be subdivided based upon the exact sutures and bones involved. Most cases of primary craniosynostosis involve only one suture. Each subdivision results in a different characteristic pattern of skull development. The subdivisions of craniosynostosis include sagittal synostosis, coronal synostosis, metopic synostosis, and lambdoid synostosis. (Synostosis is a medical term for the fusion of bones that are normally separate.)

The most common form of craniosynostosis is sagittal synostosis (hardening of the sagittal suture). The sagittal suture is the joint that runs from the front to the back of the skull and that separates the two bones that form the sides of the skull (parietal bones). Premature closure of this suture results in an abnormally long, narrow head (scaphocephaly).

Coronal synostosis refers to the premature closure of one of the coronal sutures, which are the joints that separates the two frontal bones from the two parietal bones. The coronal sutures extend across the skull, almost from one ear to the other. The two coronal sutures meet at the "soft spot" (anterior fontanelle) located toward the front and of the skull. The skull may appear twisted or lopsided and the forehead and orbit of the eye may appear flattened on one side. The forehead on the opposite side may appear to bulge. This specific skull shape is sometimes referred to as frontal plagiocephaly. When both coronal sutures are involved, it causes the skull to appear abnormally short and disproportionally wide (brachycephaly).

Metopic synostosis refers to the premature fusion of the metopic suture, which is the joint that separates the two frontal bones of the skull. It runs from the top of the forehead to the anterior fontanelle (frontal soft spot). This condition causes a keel-shaped forehead and eyes that are set closer together than normal (hypotelorism). When viewed from above the skull may appear to be shaped triangularly, a condition referred to as trigonocephaly. A ridge may be apparent running down the middle of the forehead, which may appear narrow. The soft spot found toward the back of the skull (anterior fontanelle) is usually absent or prematurely closed. The presence of a metopic ridge (a palpable/ visible prominence over the midline of the forehead) is not uncommon and not all individuals with this ridge have trigonocephaly.

Lambdoid synostosis, also known as posterior plagiocephaly, is the premature fusion of the lambdoid suture, which is the joint that separates the bone that forms the lower back of the skull (occipital bone) from the parietal bones. One side of the rear of the head may appear flatter than the other when viewed from above. The ear on the affected side may be pulled backward and stick out farther than the other ear. A small bump may also be present behind the ear on the affected side. Whereas true lambdoid synostosis is extremely rare (1/200,000), this should not be confused with the nearly ubiquitous lambdoid positional plagiocephaly. Fortunately, there are physical features that help to differentiate these two conditions.

In rare cases, individuals with primary craniosynostosis have premature fusion of multiple sutures. A specific form of craniosynostosis involving multiple sutures is known as Kleeblattschadel (which is German for cloverleaf) deformity. Fusion of multiple sutures causes the skull to appear flattened and divided into three lobes, thus resembling a cloverleaf. Kleeblattschadel deformity usually occurs as part of a syndrome.

Causes

The exact cause of primary (isolated) craniosynostosis is unknown. Primary isolated craniosynostosis refers to cases that are not associated with a larger syndrome. Most cases occur randomly for no apparent reason (sporadically) although an infant's position in utero, large size and presence of twins have all been implicated as etiological factors. A variety of different genetic and environmental factors are suspected to play a role in the development of primary isolated craniosynostosis.

In extremely rare cases, primary isolated craniosynostosis is genetic and in such cases is usually inherited as an autosomal dominant trait. Most cases of primary craniosynostosis that occur as part of a syndrome are also inherited as autosomal dominant traits. Genetic diseases are determined by the combination of genes for a particular trait that are on the chromosomes received from the father and the mother. Dominant genetic disorders occur when only a single copy of an abnormal gene is necessary for the appearance of the disease. The abnormal gene can be inherited from either parent, or can be the result of a new mutation (gene change) in the affected individual. The risk of passing the abnormal gene from affected parent to offspring is 50 percent for each pregnancy regardless of the sex of the resulting child.

The most widely accepted theory for the development of primary craniosynostosis is a primary defect in the ossification (hardening) of the cranial bones. The underlying cause of this defect is unknown in primary isolated craniosynostosis. In the syndromic forms, the defect is due to a mutation in a specific gene. Syndromic forms of primary craniosynostosis include Apert syndrome, Crouzon syndrome, Pfeiffer syndrome, Jackson-Weiss syndrome and Saethre-Chotzen syndrome. (For more information on these disorders, choose the specific disorder name as your search term in the Rare Disease Database.)

Affected Populations

Primary craniosynostosis affects individuals of all races and ethnicities and is usually present at birth. Most forms of primary craniosynostosis affect men and women in equal numbers (although males outnumber females 2:1 for sagittal synostosis). Primary craniosynostosis affects approximately 0.6 in 100,000 people in the general population. Overall, craniosynostosis affects approximately 1 in 2,000-2,500 people in the general population. Approximately 80-90 percent of individuals with primary craniosynostosis have isolated defects. The remaining cases of primary craniosynostosis occur as part of a larger syndrome. More than 150 different syndromes have been identified that are potentially associated with craniosynostosis.

Related Disorders

Symptoms of the following disorders can be similar to those of primary craniosynostosis. Comparisons may be useful for a differential diagnosis.

Secondary craniosynostosis refers to the development of an abnormal skull shape due to the premature closure of the cranial sutures that occurs because of a primary failure of brain growth. Proper brain growth pushes the bones of the skull apart, a normal process to allow the skull to accommodate the growing brain. Failure of proper brain growth allows the bones to fuse together prematurely. A variety of different underlying causes can result in the failure of brain growth and subsequent craniosynostosis. These causes include metabolic disorders, certain blood (hematological) disorders, malformation disorders, and the exposure of the fetus to certain drugs including valproic acid or phenytoin. Secondary craniosynostosis is usually associated with additional symptoms including facial abnormalities, developmental delays and microcephaly, a condition in which the head circumference is smaller than would be expected for an infant's age and sex.

Deformational (positional) plagiocephaly, sometimes known as positional plagiocephaly, is a condition in which the skull becomes misshapen due to repeated or constant pressure on a specific area of the skull. Deformational (positional) plagiocephaly is not associated with premature fusion of cranial sutures. It is caused by external forces acting on an infant's skull. It can develop before birth or after birth. The incidence of deformational (positional) plagiocephaly has increased since the American Academy of Pediatrics recommended that newborns sleep on their backs to prevent sudden infant death syndrome. This repetitive sleeping pattern results in the flattening of the back of the infant's head. Deformational plagiocephaly is not associated with any other abnormalities and does not affect a child's development.

Standard Therapies

Diagnosis
A diagnosis of primary craniosynostosis is made based upon identification of characteristic symptoms, a detailed patient history, and a thorough clinical evaluation that includes careful assessment of the shape of the skull. A variety of specialized tests include specialized imaging techniques. Such imaging techniques may include computerized tomography (CT) scanning and magnetic resonance imaging (MRI), although a head CT is best for evaluating suture / bone involvement. During CT scanning, a computer and x-rays are used to create a film showing cross-sectional images of certain tissue structures. Routine skull x-rays have been discontinued as a routine diagnostic tool in the setting of craniosynostosis due to the lack of sensitivity and frequent inaccuracy.

In some cases, a diagnosis of primary craniosynostosis may be made before birth (prenatally) by ultrasound examination. During an ultrasound, reflected sound waves create an image of the developing fetus. An increasing number of children are also being diagnosed via prenatal MRI.

Treatment
The treatment of primary craniosynostosis is directed toward the specific symptoms that are apparent in each individual. Surgery is the main form of therapy for affected children, but not all children will require surgery. Surgery is performed to create and ensure that there is enough room within the skull for the developing brain to grow; to relieve intracranial pressure (if present); and to improve the appearance of an affected child's head.

Genetic counseling may be of benefit for affected individuals and their families. Other treatment is symptomatic and supportive.

Investigational Therapies

Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.

For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:

Tollfree: (800) 411-1222
TTY: (866) 411-1010
Email: prpl@cc.nih.gov

For information about clinical trials sponsored by private sources, contact:
www.centerwatch.com

For information about clinical trials conducted in Europe, contact:
https://www.clinicaltrialsregister.eu/

Contact for additional information about primary craniosynostosis:

Robert F. Keating, MD
Professor and Chief
Department of Neurosurgery

President, Medical Staff
Children's National Medical Center

111 Michigan Ave., NW
Washington, D.C. 20010
Phone (202) 476-3020
Fax (202) 476-3091
rkeating@cnmc.org

Primary Craniosynostosis Resources

Please note that some of these organizations mat provide information concerning certain conditions potentially associated with this disorder.

NORD Member Organizations:

(To become a member of NORD, an organization must meet established criteria and be approved by the NORD Board of Directors. If you're interested in becoming a member, please contact Susan Olivo, Membership Manager, at solivo@rarediseases.org.)

Other Organizations:

References

TEXTBOOKS
Seruya M, Magge S, Keating RF. Diagnosis and Surgical Options for Craniosynostosis. Rengachary SS and Ellenbogen RA ed., In: Principles of Neurosurgery, 3rd edition. Saunders. 2012.
Lin KYK. Long MD. Primary Craniosynostosis. NORD Guide to Rare Disorders. Lippincott Williams & Wilkins. Philadelphia, PA. 2003:174.

Bixler D, Ward RE. Craniosynostosis. In: Vinken PJ, Bruyn GW, Klawans HL, eds. Handbook of Clinical Neurology. Amsterdam: Elsevier Science B.V.; 1987:113-128.

JOURNAL ARTICLES
Johnson D and Wilkie AOM. Craniosynostosis. European Journal of Human Genetics. 2011;19:369–376.
Seruya M, Oh AK , Boyajian, MJ, Posnick JC, Myseros JS, Yaun AL, Keating RF. Long-term outcomes of primary craniofacial reconstruction for craniosynostosis: a 12-year Experience. Plast Reconst Surg. 2011;127(6):2397-406.

Fearon JA, Ruotolo RA, Kolar JC. Single sutural craniosynostosis: surgical outcomes and long-term growth. Plast Reconstr Surg. 2009;123:635-642.

Pearson GD, Havlik RJ, Eppley B, Nykiel M, Sadove AM. Craniosynostosis: a single institution's outcome assessment from surgical reconstruction. J Craniofac Surg. 2008;19:65-71.

Kabbani H, Raghuveer TS. Craniosynostosis. Am Fam Physician. 2004;69:2863-2870.

INTERNET
Sheth RD Aldana PR, Iskandar BJ. Craniosynostosis. Medscape. Updated: Dec 4, 2013. Available at: http://emedicine.medscape.com/article/1175957-overview Accessed Feb 6, 2014.

National Institute of Neurological Disorders and Stoke. Craniosynostosis Information Page. September 16, 2011. Available at: http://www.ninds.nih.gov/disorders/craniosynostosis/craniosynostosis.htm Accessed Feb 6, 2014.

Mayo Clinic for Medical Education and Research. Craniosynostosis. Sep. 30, 2013. Available at: http://www.mayoclinic.com/health/craniosynostosis/DS00959 Accessed Feb 6, 2014.

The information in NORD’s Rare Disease Database is for educational purposes only. It should never be used for diagnostic or treatment purposes. If you have questions regarding a medical condition, always seek the advice of your physician or other qualified health professional. NORD’s reports provide a brief overview of rare diseases. For more specific information, we encourage you to contact your personal physician or the agencies listed as “Resources” on this report.

Report last updated: 2014/02/12 00:00:00 GMT+0

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