Rare Nephrology News

Disease Profile

Apert syndrome

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.

1-9 / 100 000

US Estimated

Europe Estimated

Age of onset

Antenatal

ICD-10

Q87.0

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease.

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype.

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder.

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

Acrocephalo-syndactyly type 1; ACS 1; Syndactylic oxycephaly;

Categories

Congenital and Genetic Diseases; Ear, Nose, and Throat Diseases; Eye diseases;

Summary

Apert syndrome is characterized by fusion of the skull bones too early during development (craniosynostosis) and webbing of fingers and toes (syndactyly). Other signs and symptoms may include distinctive facial features, some of which may lead to dental and vision problems. People with Apert syndrome may also have mild to moderate intellectual disability.[1][2] 

Apert syndrome is caused by a change (mutation) in the FGFR2 gene. It is inherited in an autosomal dominant manner, but many cases result from a new mutation in a person with no family history of the disorder (a de novo mutation).[1][2][3]

Treatment options depend on the symptoms in each person and may include surgery to separate the skull bones and relieve the pressure on the brain. The long-term outlook for a person with Apert syndrome can be improved with prompt diagnosis and medical attention.[2][3]

Symptoms

Apert syndrome is primarily characterized by a fusion of the skull bones that occurs too early during development (craniosynostosis) and webbing of the fingers and toes (syndactyly).[2] The early fusion of the skull causes the head to be cone-shaped (acrocephaly). This can also lead to a sunken appearance in the middle of the face (midface hypoplasia), wide-set eyes (hypertelorism), and a "beaked" nose. An underdeveloped upper jaw and shallow eye sockets can cause dental and vision problems. Craniosynostosis can also affect the development of the brain, disrupting intellectual development. Cognitive abilities in people with Apert syndrome range from normal to mild or moderate intellectual disability.[2][4][5] 

Additional signs and symptoms of Apert syndrome may include hearing loss, extra fingers or toes (polydactyly), heavy sweating (hyperhidrosis), oily skin with severe acne, patches of missing hair in the eyebrows, and spinal bones in the neck (cervical vertebrae) that are fused. Recurrent ear infections may be associated with an opening in the roof of the mouth (a cleft palate).[2][4][5]

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Acrobrachycephaly
0004487
Brachyturricephaly
High, prominent forehead
0000244
Broad forehead
Increased width of the forehead
Wide forehead

[ more ]

 0000337
Conductive hearing impairment
Conductive deafness
Conductive hearing loss

[ more ]

 0000405
Depressed nasal bridge
Depressed bridge of nose
Flat bridge of nose
Flat nasal bridge
Flat, nasal bridge
Flattened nasal bridge
Low nasal bridge
Low nasal root

[ more ]

 0005280
Finger syndactyly
0006101
Flat face
Flat facial shape
0012368
Frontal bossing
0002007
Hypoplasia of the maxilla
Decreased size of maxilla
Decreased size of upper jaw
Maxillary deficiency
Maxillary retrusion
Small maxilla
Small upper jaw
Small upper jaw bones
Upper jaw deficiency
Upper jaw retrusion

[ more ]

 0000327
Proptosis
Bulging eye
Eyeballs bulging out
Prominent eyes
Prominent globes
Protruding eyes

[ more ]

 0000520
Toe syndactyly
Fused toes
Webbed toes

[ more ]

 0001770
30%-79% of people have these symptoms
Absent septum pellucidum
0001331
Agenesis of corpus callosum
0001274
Aplasia/Hypoplasia of the thumb
Absent/small thumb
Absent/underdeveloped thumb

[ more ]

 0009601
Broad thumb
Broad thumbs
Wide/broad thumb

[ more ]

 0011304
Cervical C5/C6 vertebrae fusion
0004635
Convex nasal ridge
Beaked nose
Beaklike protrusion
Hooked nose
Polly beak nasal deformity

[ more ]

 0000444
Delayed eruption of teeth
Delayed eruption
Delayed teeth eruption
Delayed tooth eruption
Eruption, delayed
Late eruption of teeth
Late tooth eruption

[ more ]

 0000684
Downslanted palpebral fissures
Downward slanting of the opening between the eyelids
0000494
Facial asymmetry
Asymmetry of face
Crooked face
Unsymmetrical face

[ more ]

 0000324
Feeding difficulties in infancy
0008872
Hypertelorism
Wide-set eyes
Widely spaced eyes

[ more ]

 0000316
Hypertension
0000822
Intellectual disability
Mental deficiency
Mental retardation
Mental retardation, nonspecific
Mental-retardation

[ more ]

 0001249
Large fontanelles
Wide fontanelles
0000239
Mandibular prognathia
Big lower jaw
Increased projection of lower jaw
Increased size of lower jaw
Large lower jaw
Prominent chin
Prominent lower jaw

[ more ]

 0000303
Midface retrusion
Decreased size of midface
Midface deficiency
Underdevelopment of midface

[ more ]

 0011800
Morphological abnormality of the semicircular canal
0011380
Narrow palate
Narrow roof of mouth
0000189
Strabismus
Cross-eyed
Squint
Squint eyes

[ more ]

 0000486
5%-29% of people have these symptoms
Abnormality of cardiovascular system morphology
0030680
Arnold-Chiari malformation
0002308
Bifid uvula
0000193
Choanal atresia
Blockage of the rear opening of the nasal cavity
Obstruction of the rear opening of the nasal cavity

[ more ]

 0000453
Cloverleaf skull
0002676
Corneal erosion
Damage to outer layer of the cornea of the eye
0200020
Ectopic anus
Abnormal anus position
0004397
Esophageal atresia
Birth defect in which part of esophagus did not develop
0002032
Hydrocephalus
Too much cerebrospinal fluid in the brain
0000238
Micromelia
Smaller or shorter than typical limbs
0002983
Optic atrophy
0000648
Ovarian neoplasm
Ovarian tumor
0100615
Postaxial hand polydactyly
Extra little finger
Extra pinkie finger
Extra pinky finger

[ more ]

 0001162
Preaxial hand polydactyly
Extra thumb
0001177
Respiratory insufficiency
Respiratory impairment
0002093
Sensorineural hearing impairment
0000407
Ventriculomegaly
0002119
Visual impairment
Impaired vision
Loss of eyesight
Poor vision

[ more ]

 0000505
Percent of people who have these symptoms is not available through HPO
Abnormal morphology of the limbic system
0007343
Acne
0001061
Anomalous tracheal cartilage
0004468
Arachnoid cyst

Diagnosis

Apert syndrome can be diagnosed based on the presence of the following features:[1][2]

  • Turribrachycephalic skull shape (cone-shaped or towering skull) which is visisbly apparent and can be confirmed by skull radiograph or head CT examination
  • Characteristic facial features including moderate-to-severe underdevelopment of the midface, bulging and wide-set eyes, "beaked" nose, underdeveloped jaw and shallow eye sockets
  • Variable hand and foot findings such as syndactyly of the fingers and toes and polydactyly

Molecular genetic testing can help to confirm the diagnosis.[6] 

 

Testing Resources

  • The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.

    Treatment

    Treatment for Apert syndrome may vary depending on the specific symptoms and severity in each person, but surgery is required to prevent complete fusion of skull bones and protect brain development.[7] Surgeries to correct symptoms affecting the brain, skull and face typically are done in stages, but the timing of surgeries as well as techniques used depend upon each child's symptoms, growth, and psychosocial development. Surgeries may be needed for the following:[7][8][9]

    • Craniosynostosis release, also called cranial vault expansion (surgery to treat the fusion of the skull bones too early in development). This is typically done at 6 to 12 months of age if the infant has normal intracranial pressure (pressure inside the skull), or earlier if the pressure is increased. In some cases, the surgeon performs an initial procedure in the first year of life to increase space within the skull before the release, in which case the release may be done after 12 months of age.
    • Midface advancement or correction, in those who need additional correction of the skull or face for problems such as a sunken appearance of the face (midface hypoplasia), abnormal shape of the skull, or abnormal positioning of the eyes (orbital dystopia). The timing of surgery for midface advancement may vary depending on each child's situation. For example, it may be recommended before the child enters school (or around 4 to 8 years of age) so as to improve appearance, with the goal of maximizing the psychological well-being of the child. However, having this surgery at this age may result in recurrence, requiring another surgery in late adolescence. Therefore, some surgeons recommend midface advancement several years later, when facial growth is almost complete and the rate of recurrence is lower.
    • Hypertelorism correction to lessen the distance between widely-spaced eyes. This may be done by removing part of the bone between the eyes (interorbital bone), and repositioning the eye sockets (orbits) closer together for improved appearance.

    Various other surgeries or treatments may also be needed. For example, people with Apert syndrome may need surgery to correct or improve the shape or position of the jaws, or for the treatment of syndactyly or other skeletal abnormalities. Orthodontic treatment may be needed when growth is complete.[8][9] Management for problems with speech, language, hearing or psychosocial issues may also be needed.[9]

    Management Guidelines

    • Project OrphanAnesthesia is a project whose aim is to create peer-reviewed, readily accessible guidelines for patients with rare diseases and for the anesthesiologists caring for them. The project is a collaborative effort of the German Society of Anesthesiology and Intensive Care, Orphanet, the European Society of Pediatric Anesthesia, anesthetists and rare disease experts with the aim to contribute to patient safety.

      Organizations

      Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

      Organizations Supporting this Disease

        Social Networking Websites

          Learn more

          These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

          Where to Start

          • MedlinePlus was designed by the National Library of Medicine to help you research your health questions, and it provides more information about this topic.
          • Genetics Home Reference (GHR) contains information on Apert syndrome. This website is maintained by the National Library of Medicine.
          • The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.

            In-Depth Information

            • GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.
            • Medscape Reference provides information on this topic. You may need to register to view the medical textbook, but registration is free.
            • MeSH® (Medical Subject Headings) is a terminology tool used by the National Library of Medicine. Click on the link to view information on this topic.
            • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
            • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
            • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
            • PubMed is a searchable database of medical literature and lists journal articles that discuss Apert syndrome. Click on the link to view a sample search on this topic.

              Selected Full-Text Journal Articles

                References

                1. Nathaniel H Robin, Marni J Falk, Chad R Haldeman-Englert. FGFR-Related Craniosynostosis Syndromes. GeneReviews. June 7, 2011; https://www.ncbi.nlm.nih.gov/books/NBK1455/.
                2. Apert syndrome. Genetics Home Reference. February 2008; https://ghr.nlm.nih.gov/condition/apert-syndrome.
                3. Hamm A, Robin N. Apert syndrome. Orphanet. October 2004; https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=87.
                4. Apert Syndrome. National Organization for Rare Disorders (NORD). 2007; https://rarediseases.org/rare-diseases/apert-syndrome/.
                5. Haldeman-Englert C. Apert syndrome. MedlinePlus. August 1, 2015; https://medlineplus.gov/ency/article/001581.htm.
                6. Chen H. Apert Syndrome Workup. Medscape. April 5, 2016; https://emedicine.medscape.com/article/941723-workup.
                7. Conrady CD, Patel BC, Sharma S. Apert Syndrome. StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; January, 2018 January, 2019; https://www.ncbi.nlm.nih.gov/books/NBK518993/.
                8. Hollier, Jr. LH. Craniosynostosis syndromes. UpToDate. Waltham, MA: UpToDate; January, 2019; https://www.uptodate.com/contents/craniosynostosis-syndromes.
                9. Mathijssen IMJ. Guideline for Care of Patients With the Diagnoses of Craniosynostosis: Working Group on Craniosynostosis. J Craniofac Surg. September, 2015; 26(6):1735–1807. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4568904/.

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