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Last updated:
February 05, 2021
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NORD gratefully acknowledges Robert F. Keating, MD, Professor and Chair, Department of Neurosurgery, Children’s National Medical Center, Washington, DC, for assistance in the preparation of this report.
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. While raised intracranial pressure is unlikely with single suture abnormalities with intelligence usually being unaffected, recent data and debate about unrecognized elevated pressure (as well as effects upon cognition) has led to considerable controversy. Until we are able to measure intracranial pressure via non-invasive means, it is likely that the surgical argument between appearance and brain pressure will continue. 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.
Primary craniosynostosis is usually apparent at birth or within a few months shortly thereafter (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 / 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 usually 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) due to the restricted sideways growth (width) of the skull.
Coronal synostosis refers to the premature closure of one of the coronal sutures, which are the joints that separate 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 whereas the opposite side of the forehead may appear to bulge as part of the brain’s unrestricted growth on this side. 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 relatively common 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 and children with positional plagiocephaly usually have compensatory overgrowth at the forehead on the same side.
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.
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.)
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.
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. Although there has been recent debate about the need for CT’s prior to surgery (and accompanying radiation), there are a number of literature reports documenting their value in ruling out other suture involvement as well as brain abnormalities. 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. In general, it is an issue of appearance versus intracranial pressure. 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. The various surgical approaches (endoscopic, Pi procedures, total calvarial reconfiguration, springs, distraction, etc) each have their unique advantages / disadvantages and are best discussed in detail with the treating physician at the time of evaluation.
Genetic counseling may be of benefit for affected individuals and their families. Other treatment is symptomatic and supportive.
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:
Toll-free: (800) 411-1222
TTY: (866) 411-1010
Email: prpl@cc.nih.gov
Some current clinical trials also are posted on the following page on the NORD website: https://rarediseases.org/living-with-a-rare-disease/find-clinical-trials/
For information about clinical trials sponsored by private sources, in the main, contact: www.centerwatch.com
For more 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 Chair
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
Please note that some of these organizations mat provide information concerning certain conditions potentially associated with this disorder.
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. Last Update Updated: Dec 04, 2018. Available at: https://emedicine.medscape.com/article/1175957-overview. Accessed Jan 21, 2021.
National Institute of Neurological Disorders and Stroke. Craniosynostosis Information Page. 2019-03-27. Available at: https://www.ninds.nih.gov/Disorders/All-Disorders/Craniosynostosis-Information-Page. Accessed Jan 21, 2021.
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