Rare Infectious Disease News

Disease Profile

Achondroplasia

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

3,310 - 29,790

US Estimated

1-9 / 100 000

5,135 - 46,215

Europe Estimated

Age of onset

Neonatal

ICD-10

Q77.4

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)

ACH; Achondroplastic dwarfism

Categories

Congenital and Genetic Diseases; Musculoskeletal Diseases

Summary

Achondroplasia is a disorder of bone growth that prevents the changing of cartilage (particularly in the long bones of the arms and legs) to bone. It is characterized by dwarfism, limited range of motion at the elbows, large head size (macrocephaly), small fingers, and normal intelligence. Achondroplasia can cause health complications such as interruption of breathing (apnea), obesity, recurrent ear infections, an exaggerated inward curve of the lumbar spine (lordosis). More serious problems include a narrowing of the spinal canal that can pinch (compress) the upper part of the spinal cord (spinal stenosis) and a buildup of fluid in the brain (hydrocephalus).[1][2] Some people with achondroplasia may have delayed motor development early on, but cognition is normal.[3] Achondroplasia is caused by mutations in the FGFR3 gene. Inheritance is autosomal dominant.[1][2] Treatment may include medication with growth hormone, and surgery aimed to correct the spine, or bone problems, as well, as to reduce the pressure inside the brain in cases of hydrocephaly.[2] Prognosis with achondroplasia is good except in cases of spinal compression at the neck.[3]

Symptoms

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
Bowing of the legs
Bowed legs
Bowed lower limbs

[ more ]

0002979
Thoracolumbar kyphosis
0005619
30%-79% of people have these symptoms
Abnormality of the shape of the midface
0430026
Anteverted nares
Nasal tip, upturned
Upturned nasal tip
Upturned nose
Upturned nostrils

[ more ]

0000463
Brachydactyly
Short fingers or toes
0001156
Central sleep apnea
0010536
Cervical spinal canal stenosis
0008445
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
Frontal bossing
0002007
Functional abnormality of the middle ear
0011452
Hearing impairment
Deafness
Hearing defect

[ more ]

0000365
Hip joint hypermobility
0045087
Infantile muscular hypotonia
Decreased muscle tone in infant
0008947
Knee joint hypermobility
Knee joint over-flexibility
0045086
Limited elbow extension
Decreased elbow extension
Elbow limited extension
Limitation of elbow extension
Limited extension at elbows
Limited forearm extension
Restricted elbow extension

[ more ]

0001377
Lumbar hyperlordosis
Excessive inward curvature of lower spine
0002938
Macrocephaly
Increased size of skull
Large head
Large head circumference

[ more ]

0000256
Obstructive sleep apnea
0002870
Parietal bossing
0000242
Short long bone
Long bone shortening
0003026
Short middle phalanx of finger
Short middle bone of finger
0005819
Short nasal bridge
Decreased length of bridge of nose
Decreased length of nasal bridge
Short bridge of nose

[ more ]

0003194
Short proximal phalanx of finger
Short innermost finger bones
0010241
Trident hand
0004060
5%-29% of people have these symptoms
Abnormality of the wing of the ilium
0011867
Acanthosis nigricans
Darkened and thickened skin
0000956
Flat acetabular roof
0003180
Hydrocephalus
Too much cerebrospinal fluid in the brain
0000238
Hypoxemia
Low blood oxygen level
0012418
Narrow greater sciatic notch
0003375
Obesity
Having too much body fat
0001513
Restrictive ventilatory defect
Stiff lung or chest wall causing decreased lung volume
0002091
Rhizomelia
Disproportionately short upper portion of limb
0008905
Thoracic hypoplasia
Small chest
Small thorax

[ more ]

0005257
Wide anterior fontanel
Wider-than-typical soft spot of skull
0000260
Percent of people who have these symptoms is not available through HPO
Autosomal dominant inheritance
0000006
Brain stem compression
0002512
Conductive hearing impairment
Conductive deafness
Conductive hearing loss

[ more ]

0000405
Flared metaphysis
Flared wide portion of long bone
0003015
Generalized joint laxity
Hypermobility of all joints
0002761
Genu varum
Outward bow-leggedness
Outward bowing at knees

[ more ]

0002970
Limited hip extension
Restricted hip extension
0003093
Lumbar kyphosis in infancy
Hunched back in infancy
Round back in infancy

[ more ]

0008414
Malar flattening
Zygomatic flattening
0000272
Megalencephaly
0001355
Midface retrusion
Decreased size of midface
Midface deficiency
Underdevelopment of midface

[ more ]

0011800
Motor delay
0001270
Neonatal short-limb short stature
Short limb dwarfism recognizable at birth
Short-limb dwarfism identifiable at birth
Short-limbed dwarfism identifiable at birth

[ more ]

0008921
Recurrent otitis media
Recurrent middle ear infection
0000403
Short femoral neck
Short neck of thighbone
0100864
Small foramen magnum
Little foramen magnum
Narrow foramen magnum

[ more ]

0002677
Spinal stenosis with reduced interpedicular distance
0005733
Upper airway obstruction
0002781

Cause

Achondroplasia is caused by mutations in the FGFR3 gene.[1][2] This gene provides instructions for making a protein that is involved in the development and maintenance of bone and brain tissue. Two specific mutations in the FGFR3 gene are responsible for almost all cases of achondroplasia. Researchers believe that these mutations cause the FGFR3 protein to be overly active, which interferes with skeletal development and leads to the disturbances in bone growth seen in this condition.[1]

Diagnosis

Making a diagnosis for a genetic or rare disease can often be challenging. Healthcare professionals typically look at a person’s medical history, symptoms, physical exam, and laboratory test results in order to make a diagnosis. The following resources provide information relating to diagnosis and testing for this condition. If you have questions about getting a diagnosis, you should contact a healthcare professional.

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

    Recommendations for management of children with achondroplasia were outlined by the American Academy of Pediatrics Committee on Genetics in the article, Health Supervision for Children with Achondroplasia. We recommend that you review this article with your child’s health care provider(s). These recommendations include:[2]

    • Monitoring of height, weight, and head circumference using growth curves standardized for achondroplasia

    • Measures to avoid obesity starting in early childhood.

    • Careful neurologic examinations, with referral to a pediatric neurologist as necessary

    • MRI or CT of the foramen magnum region for evaluation of severe hypotonia or signs of spinal cord compression

    • Obtaining history for possible sleep apnea, with sleep studies as necessary

    • Evaluation for low thoracic or high lumbar gibbus if truncal weakness is present

    • Referral to a pediatric orthopedist if bowing of the legs interferes with walking

    • Management of frequent middle-ear infections

    • Speech evaluation by age two years

    • Careful monitoring of social adjustment

    The GeneReview article on achondroplasia also provides information on medical management.
    https://www.ncbi.nlm.nih.gov/books/NBK1152/#achondroplasia.Management

    Management Guidelines

    • The National Guideline Clearinghouse (NGC) is a public resource for evidence-based clinical practice guidelines. The NGC was originally created by the Agency for Healthcare Research and Quality (AHRQ) in partnership with the American Medical Association and the American Association of Health Plans.
    • 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

        Organizations Providing General Support

          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

          • John's Hopkins Medicine has an information page on this topic. Click on the link above to view the information page.
          • MedlinePlus was designed by the National Library of Medicine to help you research your health questions, and it provides more information about this topic.
          • MedlinePlus Genetics contains information on Achondroplasia. This website is maintained by the National Library of Medicine.
          • The National Human Genome Research Institute's (NHGRI) website has an information page on this topic. NHGRI is part of the National Institutes of Health and supports research on the structure and function of the human genome and its role in health and disease.
          • 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.
            • 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 Achondroplasia. Click on the link to view a sample search on this topic.

              Selected Full-Text Journal Articles

                References

                1. Achondroplasia. Genetics Home Reference. May 2012; https://ghr.nlm.nih.gov/condition=achondroplasia.
                2. Pauli RM. Achondroplasia. GeneReviews. February 2012; https://www.ncbi.nlm.nih.gov/books/NBK1152/.
                3. Bacino CA. Achondroplasia. UpToDate. November 15, 2017; https://www.uptodate.com/contents/achondroplasia.
                4. Learning About Achondroplasia. National Human Genome Research Institute (NHGRI). May 11, 2012; https://www.genome.gov/19517823.
                5. Defendi GL. Genetics of Achondroplasia. Medscape Reference. May 16, 2014; https://emedicine.medscape.com/article/941280-overview.
                6. Totter TL, Hall JG, Committee on Genetics. Pediatrics. 2005; 116:771. https://pediatrics.aappublications.org/content/pediatrics/116/3/771.full.pdf.

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