Apert Syndrome

Apert Syndrome

National Organization for Rare Disorders, Inc.

Important

It is possible that the main title of the report Apert Syndrome is not the name you expected. Please check the synonyms listing to find the alternate name(s) and disorder subdivision(s) covered by this report.

Synonyms

  • Acrocephalosyndactyly, Type I
  • ACS I
  • Syndactylic Oxycephaly
  • ACS1

Disorder Subdivisions

  • None

General Discussion

Apert syndrome, also known as acrocephalosyndactyly type I (ACS1), is a rare genetic disorder that is apparent at birth (congenital). The disorder is character-ized by distinctive malformations of the head that lead to distinctive facial features. In addition, the hands and/or feet may be webbed (syndactyly) and in some cases, mental retardation may also be present.



Among babies born with Apert syndrome, the fibrous joints between bones of the skull (sutures) close prematurely (craniosynostosis). The pressure of continued brain growth distorts various bones of the skull and the face. The skull is forced into one of several characteristic shapes. Often the head appears abnormally pointed at the top (acrocephaly). The distortion of the skull plates create changes in the facial bones leading to characteristic facial abnormalities, such as widely spaced eyes (ocular hypertelorism), abnormal protrusion of the eyes (exophthalmos), underdevelopment of midfacial regions (midface hypoplasia), and/or a narrow roof of the mouth (palate).



Malformations of the hands and feet may include unusually broad thumbs and great toes, short fingers, and/or partial to complete fusion (syndactyly) of certain fingers and toes (digits). Most commonly, there is complete fusion of bones within the second to the fourth fingers and the presence of a single common nail ("mitten-like" syndactyly).



In almost all instances, Apert syndrome results from new genetic changes (mutations) that appear to occur randomly for unknown reasons (sporadically). In rare cases, the disorder may be inherited as an autosomal dominant trait.

Symptoms

Apert syndrome is characterized by premature closure of the fibrous joints (cranial sutures) between certain bones in the skull (craniosynostosis) and malformations of the face, hands, and feet. The degree of craniosynostosis may be variable and depend on the specific cranial sutures involved. However, in most affected individuals, there is premature fusion of the suture (i.e., coronal suture) between the bones forming the forehead and the upper sides of the skull (i.e., frontal and parietal bones). As a result, the head tends to appear abnormally pointed at the top (acrocephaly) and the diameter from the front to the back of the skull (anterior-posterior diameter) may be shortened. In addition, the back portion of the skull (occiput) may appear flattened and the forehead is unusually prominent.



Apert syndrome is also characterized by partial to complete fusion (syndactyly) of certain fingers and toes (digits). The syndactyly may involve soft tissues only (cutaneous syndactyly) or include fusion of bone (osseous syndactyly). In many affected individuals, there is complete fusion of the second, third, and fourth fingers and the presence of a single, continuous nail (synonychia). However, in some instances, the thumb and the fifth finger (or "pinky") may also be involved. The bones of the ends of the thumbs (distal phalanges) tend to be unusually broad and may deviate outward (valgus deformity), and the fingers are often unusually short (brachydactyly). In addition, finger joints tend to become stiff by about four years of age. Syndactyly also typically involves the second, third, and fourth toes. The toenails may be partially continuous or separate. Some affected individuals may have syndactyly involving the fifth toes and the great toes; unusually broad, deviating great toes (hallux varus); or other bony abnormalities.



In addition to these characteristic signs and symptoms, Apert syndrome affects several other organ systems of the body. The database, Online Mendelian Inheritance in Man, presents the following as a Clinical Synopsis of Apert syndrome:



* Growth

Decrease in the rate of growth leading to short stature, in spite of normal birth weight and birth length



* Head and Neck

Head

Pointed but broad skull

Large, late-closing "soft spot" on the skull (fontanelle)



* Face

High, broad forehead

Flat face

Jutting jaw

Right and left asymmetry



* Ears

Hearing loss

Chronic ear infections (otitis media)



* Eyes

Shallow orbits in which the eyes sit

Wide separation between eyes

Down-slanting eyelids

Bulging eyes

Cross-eyes



* Nose

Flattened nose with low bridge

The openings between the nose and throat (choana) may be blocked or narrowed, interfering with breathing and swallowing.



* Mouth

Narrow "roof" of the mouth (palate)

Cleft palate especially of the form known as "bifid uvula"



* Teeth

Bad "bite" (malocclusion)

Delayed dentition teeth are late in coming



* Cardiovascular

Hole(s) in ventricular wall

Overriding aorta develops when the aorta is positioned directly over a hole in ventricular wall, instead of over the left ventricle. As a result, the aorta contains some blood from the right ventricle reducing the amount of oxygen transported.



* Respiratory

Malformed cartilage supports of the trachea, interfering with breathing and swallowing



* Abdomen

Narrowing of the opening between the lower part of the stomach and the upper part of the small intestine (duodenum).

Blockage of the esophagus

Anus out of position



* Genitourinary

Failure of the testicles to fall

Blockage of vagina

Enlarged kidneys due to blockage



* Skeletal

Fusion of cervical vertebrae (C5 and C6)

Fusion of the two bones of the arms

Fusion of bones of the wrist

Fusion (syndactyly) of the bones and/or skin of hands and feet

Spatulate end joint of the thumb



* Skin, Nails & Hair

Moderate to severe acne

Single nail across the fused digits from 2-4



* Neurologic

Varying degrees of mental retardation

Failure to form the fibrous tissue that joins the cerebral hemispheres of the brain

Enlarged brain cavity

Failure to form the membranes that separate the various cavities of the brain

Malformations of parts of the brain's limbic system that deals in part with the autonomous nervous system

Causes

In most affected individuals, Apert syndrome results from new genetic changes (mutations) that appear to occur randomly for unknown reasons (sporadically). According to reports in the medical literature, sporadic cases may be associated with increased age of the father advanced paternal age). Estimates suggest that as many as 95% of new cases may be due to sporadic mutations.



Rarely, the disorder may be inherited as an autosomal dominant trait. Human traits, including the classic genetic diseases, are the product of the interaction of two genes, one received from the father and one from the mother.



In dominant disorders, a single copy of the disease gene (received from either the mother or father) will be expressed "dominating" the other normal gene and resulting in the appearance of the disease. The risk of transmitting the disorder from affected parent to offspring is 50 percent for each pregnancy regardless of the sex of the resulting child. The risk is the same for each pregnancy.



Researchers have shown that Apert syndrome results from certain mutations in a gene known as fibroblast growth factor receptor-2 (FGFR2). According to reports in the medical literature, in almost all cases, the disorder appears to be caused by one of two specific mutations of the FGFR2 gene. (These mutations are designated "Ser252Trp" and "Pro253Arg.") The gene has been mapped to the long arm (q) of chromosome 10 (10q26). Chromosomes are found in the nucleus of all body cells. They carry the genetic characteristics of each individual. Pairs of human chromosomes are numbered from 1 through 22, with an unequal 23rd pair of X and Y chromosomes for males and two X chromosomes for females. Each chromosome has a short arm designated as "p" and a long arm identified by the letter "q". Chromosomes are further subdivided into bands that are numbered.



Evidence indicates that different mutations in the FGFR2 gene may cause a number of other related disorders, including some cases of Pfeiffer syndrome, Crouzon syndrome, and Jackson-Weiss syndrome. (For further information on these disorders, please see the "Related Disorders" section of this report below.)

Affected Populations

Apert syndrome appears to affect males and females in relatively equal numbers. Since the disorder was originally described in the medical literature in 1894 (Wheaton SW) and 1906 (Apert E), over 300 cases have been reported. The disorder is estimated to occur in about one in 165,000 to 200,000 births.

Standard Therapies

Diagnosis

In some instances, a diagnosis of Apert syndrome may be suggested before birth (prenatally) by specialized testing, such as fetoscopy or ultrasound. During fetoscopy, a flexible viewing instrument (endoscope) may be introduced into the uterus through the abdominal wall to directly observe the fetus and, in some cases, to obtain fetal blood or tissue samples (e.g., for DNA analysis). Fetal ultrasonography is a noninvasive diagnostic procedure during which reflected sound waves are used to create an image of the developing fetus.



In most cases, the diagnosis is made or confirmed at birth or during early infancy based upon a thorough clinical evaluation, identification of characteristic physical findings, and a variety of specialized tests (e.g., molecular DNA analysis). Advanced imaging techniques, such as computerized tomography (CT) scanning or magnetic resonance imaging (MRI), or other diagnostic tests may be used to help detect or characterize certain abnormalities that may be associated with the disorder (e.g., skeletal abnormalities, hearing impairment, congenital heart defects, etc.).



Treatment

The treatment of Apert syndrome is directed toward the specific symptoms that are apparent in each individual. Such treatment may require the coordinated efforts of a team of medical professionals, such as pediatricians; surgeons, physicians who diagnose and treat disorders of the skeleton, joints, muscles, and related tissues (orthopedists), physicians who specialize in disorders of the ears, nose, and throat (otolaryngologists), physicians who diagnose and treat heart abnormalities (cardiologists), hearing specialists, and/or other health care professionals.



Specific therapies for Apert syndrome are symptomatic and supportive. Craniosynostosis and, in some cases, associated hydrocephalus may result in abnormally increased pressure within the skull (intracranial pressure) and on the brain. In such cases, early surgery (within 2 to 4 months after birth) may be advised to correct craniosynostosis and, for those with hydrocephalus, to insert a tube (shunt) to drain excess cerebrospinal fluid (CSF) away from the brain and into another part of the body where the CSF can be absorbed. Early corrective and reconstructive surgery may also be performed in some infants with Apert syndrome to help correct certain associated craniofacial abnormalities.



Additional surgical and/or medical treatment may be required to treat and correct other symptoms.



Genetic counseling will be of benefit for affected individuals and their families. Other treatment for this disorder 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

References

TEXTBOOKS

Long MD, Lin KYK. In: NORD Guide to Rare Disorders. Lippincott Williams & Wilkins. Philadelphia, PA. 2003:154-55.



Gorlin RJ, Cohen MMJr, Hennekam RCM. Eds. Syndromes of the Head and Neck. 4th ed. Oxford University Press, New York, NY; 2001:654.



Jones KL. Smith's Recognizable Patterns of Human Malformation. 5th ed. Philadelphia, PA: W.B. Saunders Company; 1997:418-19.



Castriota-Scanderberg A, Dallapiccola B. Abnormal Skeletal Phenotypes. Springer Verlag. Berlin, Germany. 2005:593.



JOURNAL ARTICLES

Lam H, Lo TK, Lau E, Chin R, Tang L. The use of 2- and 3- dimensional sonographic scans in the evaluation of cranial sutures: prenatal diagnosis of apert syndrome. J Ultrasound Med. 2006;25:1481-84.



Wryobek AJ, Eskenazi B, Young S, Arnheim M, et al. Advancing age has differential effects on DNA damage, chromatin integrity, gene mutations, and aneuploidies in sperm. Proc Natl. Acad Sci U S A 2006;103:9601-606.



Quintero-Rivera F, Robson CD, Reiss RE, Levine D, et al. Intracranial anomalies detected by imaging studies in 30 patients with Apert syndrome. Am J Med Genet A. 2006;140:1337-38.



Meling TR, Hans-Erik H, Per S, Due-Tonnessen BJ. Le Fort III distraction osteogenesis in syndrome craniosynostosis. J Craniofac Surg. 2006;17:28-39.



Schulten A, Lim AA, Bruun RA, Hayes C, Mulliken JB, Padwa BL. Combined push-pull distraction for correction of syndromic midfacial hypoplasia. J Oral Maxillofac Surg. 2006;64:23-30.



Guero SJ. Algorithm for treatment of apert hand. Tech hand Up Extrem Surg. 2005;9:126-33.



Sgouros S. Skull vault growth in craniosynostosis. Childs Nerv Syst. 2005;21:861-70.



Ibrahami OA, Chiu ES, McCarthy JG, Mohammadi M. Plast Reconstr Surg. 2005;115:264-70.



Kubbani H, Raghuveer TS. Am Fam Physician. 2004;69:2863-74.



Panchal J, Uttchin V. Management of Craniosynostosis. Plast Reconstr Surg. 2003;111:2032-49.



FROM THE INTERNET

McKusick VA, Ed. Online Mendelian Inheritance in Man (OMIM). The Johns Hopkins University. Apert Syndrome. Entry Number; 101200: Last Edit Date; 10/12/2006.



Sindheimer N. Apert syndrome. Medical Encyclopedia. MedlinePlus. Update Date: 4/20/2005. 3pp.

www.nlm.nih.gov/medlineplus/ency/article/001581.htm

Accessed 10/25/2006



Apert syndrome. Genetics Home Reference. Published: October 20, 2006. 4pp.

http://ghr.nlm.gov/condition=apertsyndrome

Accessed 10/25/2006

Resources

Children's Craniofacial Association

13140 Coit Road

Suite 517

Dallas, TX 75240

USA

Tel: (214)570-9099

Fax: (214)570-8811

Tel: (800)535-3643

Email: contactCCA@ccakids.com

Internet: http://www.ccakids.com



FACES: The National Craniofacial Association

PO Box 11082

Chattanooga, TN 37401

Tel: (423)266-1632

Fax: (423)267-3124

Tel: (800)332-2373

Email: faces@faces-cranio.org

Internet: http://www.faces-cranio.org



The Arc

1825 K Street NW, Suite 1200

Washington, DC 20006

Tel: (202)534-3700

Fax: (202)534-3731

Tel: (800)433-5255

TDD: (817)277-0553

Email: info@thearc.org

Internet: http://www.thearc.org



Let's Face It

University of Michigan, School of Dentistry / Dentistry Library

1011 N. University

Ann Arbor, MI 48109-1078

USA

Tel: (360)676-7325

Email: faceit@umich.edu

Internet: http://www.dent.umich.edu/faceit



AmeriFace

P.O. Box 751112

Limekiln, PA 19535

USA

Tel: (702)769-9264

Fax: (702)341-5351

Tel: (888)486-1209

Email: info@ameriface.org

Internet: http://www.ameriface.org



Apert Syndrome Support Group

8708 Kathy

St. Louis, MO 63126

Tel: (314)965-3356

Internet: http://www.dailystrength.org/c/Apert-Syndrome/support-group



American Heart Association

7272 Greenville Avenue

Dallas, TX 75231

Tel: (214)784-7212

Fax: (214)784-1307

Tel: (800)242-8721

Email: Review.personal.info@heart.org

Internet: http://www.heart.org



National Foundation for Facial Reconstruction

333 East 30th Street, Lobby Unit

New York, NY 10016

Tel: (212)263-6656

Fax: (212)263-7534

Internet: http://www.nffr.org



Craniofacial Clinic at University of Virginia

University of Virginia Medical Center

Dept. of Plastic and Maxillofacial Surgery

Box 376

Charlottesville, VA 22908

Tel: (434)924-2528

Email: tjg6f@virginia.edu

Internet: http://www.medicine.virginia.edu/



Danish Apert Syndrome Association (Danmarks Apertforening)

Dronningeengen 17

Vedbaek, DK-2950

Denmark

Tel: 4545890300

Fax: 4545890350

Email: soeren@lildal.com



Craniofacial Foundation of America

975 East Third Street

Chattanooga, TN 37403

Tel: (423)778-9176

Fax: (423)778-8172

Tel: (800)418-3223

Email: terry.smyth@erlanger.org

Internet: http://www.craniofacialfoundation.org



AboutFace International

123 Edward Street, Suite 1003

Toronto

Ontario, M5G 1E2

Canada

Tel: 4165972229

Fax: 4165978494

Tel: 8006653223

Email: info@aboutfaceinternational.org

Internet: http://www.aboutface.ca/



Headlines - Craniofacial Support Group

128 Beesmoor Road

Frampton Cotterell

Bristol, BS36 2JP

United Kingdom

Tel: 01454850557

Email: info@headlines.org.uk

Internet: http://www.headlines.org.uk



Genetic and Rare Diseases (GARD) Information Center

PO Box 8126

Gaithersburg, MD 20898-8126

Tel: (301)251-4925

Fax: (301)251-4911

Tel: (888)205-2311

TDD: (888)205-3223

Internet: http://rarediseases.info.nih.gov/GARD/



Madisons Foundation

PO Box 241956

Los Angeles, CA 90024

Tel: (310)264-0826

Fax: (310)264-4766

Email: getinfo@madisonsfoundation.org

Internet: http://www.madisonsfoundation.org



For a Complete Report

This is an abstract of a report from the National Organization for Rare Disorders, Inc.® (NORD). Cigna members can access the complete report by logging into myCigna.com. For non-Cigna members, a copy of the complete report can be obtained for a small fee by visiting the NORD website. The complete report contains additional information including symptoms, causes, affected population, related disorders, standard and investigational treatments (if available), and references from medical literature. For a full-text version of this topic, see http://www.rarediseases.org/search/rdblist.html.

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