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, MD, PhD
Department of Pediatrics
University of Wisconsin – Madison
Madison, Wisconsin

Initial Posting: ; Last Update: February 16, 2012.


Clinical characteristics.

Achondroplasia is the most common process resulting in disproportionate small stature. Affected individuals have short arms and legs, a large head, and characteristic facial features with frontal bossing and midface retrusion (formerly known as midface hypoplasia). In infancy, hypotonia is typical, and acquisition of developmental motor milestones is often both aberrant in pattern and delayed. Intelligence and life span are usually near normal, although craniocervical junction compression increases the risk of death in infancy.


Achondroplasia can be diagnosed by characteristic clinical and radiographic findings in most affected individuals. In individuals in whom there is diagnostic uncertainty or atypical findings, molecular genetic testing can be used to detect a pathogenic variant in FGFR3, the only gene known to be associated with achondroplasia. Such testing detects pathogenic variants in 99% of affected individuals.


Treatment of manifestations: Ventriculoperitoneal shunt may be required for increased intracranial pressure; suboccipital decompression as indicated for signs and symptoms of craniocervical junction compression; adenotonsillectomy, positive airway pressure, and, rarely, tracheostomy to correct obstructive sleep apnea; aggressive management of middle-ear dysfunction; evaluation by an orthopedist if progressive bowing of the legs arises; surgery to correct spinal stenosis in symptomatic adults; and educational support in socialization and school adjustment.

Surveillance: Monitor height, weight, and head circumference in childhood using growth curves standardized for achondroplasia; evaluation of developmental milestones throughout infancy and childhood; baseline CT scan of the brain in infancy; monitor for signs and symptoms of sleep apnea; monitor for middle ear problems or evidence of hearing loss in childhood; clinical assessment for kyphosis and bowed legs, with radiographic evaluation and referral to an orthopedist, if necessary; in adults, clinical history and neurologic examination to screen for spinal stenosis every three to five years.

Agents/circumstances to avoid: Activities in which there is risk of injury to the craniocervical junction, such as collision sports; use of a trampoline; diving from diving boards; vaulting in gymnastics; and hanging upside down from the knees or feet on playground equipment.

Pregnancy management: Pregnant women with achondroplasia must undergo caesarean section delivery because of small pelvic size.

Genetic counseling.

Achondroplasia is inherited in an autosomal dominant manner. Around 80% of individuals with achondroplasia have parents with average stature and have achondroplasia as the result of a de novo pathogenic variant. Such parents have a low risk of having another child with achondroplasia. An individual with achondroplasia who has a reproductive partner with average stature has a 50% risk in each pregnancy of having a child with achondroplasia. When both parents have achondroplasia, the risk to their offspring of having average stature is 25%; of having achondroplasia, 50%; and of having homozygous achondroplasia (a lethal condition), 25%. Prenatal testing for pregnancies at increased risk is possible once the pathogenic variant has been identified in the family.


Clinical Diagnosis

Both the clinical and radiologic features of achondroplasia have been well defined [Langer et al 1967], although no formal diagnostic algorithms have been published.

The clinical features of achondroplasia include the following:

  • Small stature
  • Rhizomelic (proximal) shortening of the arms and legs with redundant skin folds on limbs
  • Limitation of elbow extension
  • Short fingers
  • Trident configuration of the hands
  • Genu varum (bow legs)
  • Thoracolumbar kyphosis in infancy
  • Exaggerated lumbar lordosis, which develops when walking begins
  • Large head with frontal bossing
  • Midfacial retrusion and depressed nasal bridge

The radiographic findings of achondroplasia in children include the following:

  • Short, robust tubular bones
  • Narrowing of the interpediculate distance of the caudal spine
  • Rounded ilia and horizontal acetabula
  • Narrow sacrosciatic notch
  • Proximal femoral radiolucency
  • Mild, generalized metaphyseal changes

Molecular Genetic Testing

Gene. FGFR3 is the only gene in which pathogenic variants are known to cause achondroplasia.

Table 1.

Summary of Molecular Genetic Testing Used in Achondroplasia

Gene 1Test MethodVariants Detected 2Variant Detection Frequency by Test Method 3
FGFR3Targeted analysis for pathogenic variantsc.1138G>A (p.Gly380Arg)~98%
c.1138G>C (p.Gly380Arg)~1%
Sequence analysis 4 of select exonsSequence variants in the selected exons 5See footnote 6
Sequence analysis 4Sequence variants in the gene 5>99% 7

See Molecular Genetics for information on allelic variants.


The ability of the test method used to detect a variant that is present in the indicated gene


Sequence analysis detects variants that are benign, likely benign, of uncertain significance, likely pathogenic, or pathogenic. Pathogenic variants may include small intragenic deletions/insertions and missense, nonsense, and splice site variants; typically, exon or whole-gene deletions/duplications are not detected. For issues to consider in interpretation of sequence analysis results, click here.


These methods should be used only when the suspicion of achondroplasia based on clinical and radiographic grounds is high and the two common pathogenic variants are not found. Typically, sequence analysis of selected exons is designed to detect the few reported pathogenic variants known to cause achondroplasia. Sequence analysis of the entire coding region detects these known pathogenic variants and also has the potential of detecting novel sequence variants, whose clinical significance may be unknown.


Includes the two pathogenic variants detected by targeted analysis


Testing Strategy

To confirm/establish the diagnosis in a proband. An individual with typical clinical and radiographic findings of achondroplasia does not generally need molecular confirmation of the diagnosis. In those in whom there is any uncertainty:

  • Targeted analysis for the two common pathogenic variants should be pursued first.
  • Sequence analysis can be performed when the suspicion of achondroplasia based on clinical and radiographic grounds is high and targeted analysis for the two common pathogenic variants is negative.

Prenatal diagnosis and preimplantation genetic diagnosis (PGD) for at-risk pregnancies require prior identification of the pathogenic variant in the family.

Clinical Characteristics

Clinical Description

Other, extensive summaries of the natural history and appropriate interventions in individuals with achondroplasia have been published [Trotter et al 2005, Pauli 2010].

Individuals with achondroplasia have short stature caused by rhizomelic shortening of the limbs, characteristic facies with frontal bossing and midfacial retrusion, exaggerated lumbar lordosis, limitation of elbow extension and rotation, genu varum, brachydactyly, and trident appearance of the hands. Excess mobility of the knees, hips, and most other joints is common.

Average adult height for men with achondroplasia is 131±5.6 cm; for women, 124±5.9 cm. Obesity is a major problem in achondroplasia [Hecht et al 1988]. Excessive weight gain is manifest in early childhood. In adults, obesity can aggravate the morbidity associated with lumbar stenosis and contribute to nonspecific joint problems and possibly to early mortality from cardiovascular complications [Hecht et al 1988].

In infancy, mild to moderate hypotonia is typical, and acquisition of developmental motor milestones is delayed and also shows unusual, aberrant patterns [Fowler et al 1997, Ireland et al 2010]. Infants have difficulty in supporting their heads because of both hypotonia and large head size.

Intelligence is normal unless hydrocephalus or other central nervous system complications occur.

True megalencephaly occurs in individuals with achondroplasia and most children with achondroplasia are macrocephalic [Horton et al 1978]. Hydrocephalus requiring treatment, which probably occurs in 5% or fewer [Pauli 2010], may be caused by increased intracranial venous pressure because of stenosis of the jugular foramina [Pierre-Kahn et al 1980, Steinbok et al 1989].

Some infants with achondroplasia die in the first year of life from complications related to the craniocervical junction; population-based studies suggest that this excess risk of death may be as high as 7.5% [Hecht et al 1987]. The risk appears to be secondary to central apnea associated with damage to respiratory control centers [Nelson et al 1988, Pauli et al 1995], and can be minimized by comprehensive evaluation of every infant with achondroplasia [Trotter et al 2005] and selective neurosurgical intervention. In one study [Pauli et al 1995] all children undergoing surgical decompression of the craniocervical junction showed marked improvement of neurologic function. Quality of life indices determined up to 20 years after such surgery were comparable to quality of life indices in those for whom surgery was not indicated in childhood [Ho et al 2004].

Obstructive sleep apnea, common in both older children and adults [Waters et al 1995, Sisk et al 1999], arises because of a combination of midfacial retrusion resulting in smaller airway size [Stokes et al 1983, Waters et al 1995], hypertrophy of the lymphatic ring and, perhaps, abnormal innervation of the airway musculature [Tasker et al 1998].

Middle ear dysfunction is frequently a problem [Berkowitz et al 1991], which, if inadequately treated, can result in hearing loss of sufficient severity to interfere with language development.

Bowing of the lower legs is exceedingly common in those with achondroplasia [Kopits 1988a]. More than 90% of untreated adults have some degree of bowing [Kopits 1988a]. ‘Bowing’ is actually a complex deformity arising from a combination of lateral bowing, internal tibial torsion and dynamic instability of the knee [Inan et al 2006].

Kyphosis at the thoracolumbar junction is present in 90%-95% of infants with achondroplasia [Kopits 1988b, Pauli et al 1997]. In about 10% it does not spontaneously resolve and can result in serious neurologic sequelae [Kopits 1988b]. Preventive strategies [Pauli et al 1997] may reduce the need for surgical intervention [Ain & Browne 2004, Ain & Shirley 2004].

The most common medical complaint in adulthood is symptomatic spinal stenosis involving L1-L4 [Kahanovitz et al 1982]. Symptoms range from intermittent, reversible, exercise-induced claudication to severe, irreversible abnormalities of leg function and of continence [Pyeritz et al 1987].

Increased mortality in adults with achondroplasia has been reported [Hecht et al 1987, Wynn et al 2007]. In the latter study, there was a tenfold increase in heart disease-related mortality between ages 25 and 35 and, overall, life expectancy appeared to be decreased by about ten years.

Homozygous achondroplasia, caused by the presence of two mutated alleles at nucleotide 1138 of FGFR3, is a severe disorder with radiologic changes qualitatively different from those of achondroplasia. Early death results from respiratory insufficiency because of the small thoracic cage and neurologic deficit from cervicomedullary stenosis [Hall 1988].

Genotype-Phenotype Correlations

Because nearly all instances of achondroplasia arise secondary to identical amino acid substitutions, genotype-phenotype correlation related to the primary pathogenic variant is not possible.


Penetrance is 100%, meaning that all individuals who have a single copy of one of the FGFR3 pathogenic variants giving rise to achondroplasia have the clinical manifestations of the disorder.


Anticipation is not observed.


Historically, the term achondroplasia was initially used to describe all individuals with short-limbed dwarfing disorders. Because achondroplasia is so common compared to other small stature processes, the term ‘dwarf’ was previously used most often to refer to an individual with achondroplasia. Over the past 40 years diagnostic criteria have been available to distinguish true achondroplasia from other, superficially similar processes.


Achondroplasia is the most common form of inherited disproportionate short stature. Best estimates are that it occurs in 1:26,000-1:28,000 live births [Oberklaid et al 1979, Orioli et al 1995].

Differential Diagnosis

While more than 100 skeletal dysplasias that cause short stature are recognized, many are extremely rare; and virtually all have clinical and radiographic features that readily distinguish them from achondroplasia. Conditions that may be confused with achondroplasia include the following:

  • Hypochondroplasia (also usually caused by pathogenic variants in FGFR3). This distinction is sometimes the most difficult to make. In fact, there appears to be some overlap between the radiologic and clinical phenotypes of these two conditions [Almeida et al 2009].
  • Cartilage-hair hypoplasia (metaphyseal chondrodysplasia, McKusick type)
  • Pseudoachondroplasia (a clinically and genetically distinct skeletal dysplasia; the similar nomenclature, however, may cause confusion)
  • Other metaphyseal dysplasias


Evaluations Following Initial Diagnosis

Clinical manifestations in achondroplasia vary modestly. In order to establish the extent of disease in an individual diagnosed with achondroplasia, the following evaluations are recommended:

  • Clinical genetics consultation and, if feasible, consultation with a clinician experienced in caring for children with bone dysplasias
  • Documentation of length, weight, and head circumference compared with achondroplasia-specific growth standards
  • Assessment of the craniocervical junction including neurologic history and examination, computerized tomography of the craniocervical junction, and polysomnography
  • Baseline computerized tomography of the brain

Treatment of Manifestations

Recommendations for management of children with achondroplasia were outlined by the American Academy of Pediatrics Committee on Genetics [Trotter et al 2005]. The recommendations of the committee are meant to supplement guidelines available for treating the child with average stature. A recent review [Pauli 2010] updates the information available in Trotter et al [2005].

The recommendations include (but are not limited to) the following:

Short stature

  • A number of studies have assessed growth hormone (GH) therapy as a possible treatment for the short stature of achondroplasia [Seino et al 2000, Kanaka-Gantenbein 2001, Kanazawa et al 2003].
    • In general, these and other series show initial acceleration of growth, but with lessening effect over time.
    • Only modest effects on adult stature seem to accrue.
  • Extended limb lengthening using various techniques remains an option for some. Increases in height of up to 12-14 inches may be obtained [Peretti et al 1995, Ganel & Horoszowski 1996, Yasui et al 1997, Aldegheri & Dall’Oca 2001].
    • Although some have advocated performing these procedures as early as ages six to eight years, many pediatricians, clinical geneticists, and ethicists have advocated postponing such surgery until the young person is able to participate in making an informed decision.
    • At least in North America, only a tiny proportion of affected individuals elect to undergo extended limb lengthening. The Medical Advisory Board of Little People of America has published a statement regarding use of extended limb lengthening.

Obesity. Measures to avoid obesity should start in early childhood.

  • Standard weight and weight-by-height grids specific for achondroplasia [Hunter et al 1996, Hoover-Fong et al 2007] should be used to monitor progress.
  • Note that the body mass index has not been standardized for individuals with achondroplasia and will yield misleading results; thus, body mass index should not be used in this population until normal ranges are established.


  • If increased intracranial pressure arises, referral to a neurosurgeon is needed.
  • Because of the presumed mechanism giving rise to hydrocephalus in this population, probably ventriculoperitoneal shunting, rather than third ventriculostomy, is appropriate.

Craniocervical junction constriction

  • The best predictors of need for suboccipital decompression include:
    • Lower-limb hyperreflexia or clonus
    • Central hypopnea demonstrated by polysomnography
    • Reduced foramen magnum size, determined by CT examination of the craniocervical junction and by comparison with the norms for children with achondroplasia [Pauli et al 1995].
  • If there is clear indication of symptomatic compression, urgent referral to a pediatric neurosurgeon for decompression surgery should be initiated [Bagley et al 2006].

Obstructive sleep apnea

  • Treatment may include the following:
    • Adenotonsillectomy
    • Weight reduction
    • Continuous positive airway pressure
    • Tracheostomy for extreme cases
  • Improvement in disturbed sleep and some improvement in neurologic function can result from these interventions [Waters et al 1995].
  • In rare instances in which the obstruction is severe enough to require tracheostomy, surgical intervention to advance the midface has been used to alleviate upper airway obstruction [Elwood et al 2003].

Middle ear dysfunction

  • Routine management of frequent middle-ear infections, persistent middle-ear fluid, and consequent hearing loss should be undertaken as needed.
  • Speech evaluation by age two years should be undertaken if any concerns arise on screening.

Varus deformity

  • Criteria for surgical intervention have been published previously [Kopits 1980, Pauli 2010].
  • Presence of progressive, symptomatic bowing should prompt referral to an orthopedist. Various interventions may be elected (e.g. valgus-producing and derotational osteotomies, guided growth using 8-plates).

Kyphosis. A protocol to help prevent the development of a fixed, angular kyphosis is available [Pauli et al 1997]:

  • In children in whom spontaneous remission does not arise after trunk strength increases and the child begins to walk, bracing is usually sufficient to prevent persistence of the thoracolumbar kyphosis.
  • If a severe kyphosis persists, spinal surgery may be necessary to prevent neurologic complications [Ain & Browne 2004, Ain & Shirley 2004].

Spinal stenosis


  • Because of the highly visible nature of the short stature associated with achondroplasia, affected persons and their families may encounter difficulties in socialization and school adjustment.
  • Support groups (see Resources), such as the Little People of America, Inc (LPA), can assist families with these issues through peer support, personal example, and social awareness programs.
  • Information on employment, education, disability rights, adoption of children with short stature, medical issues, suitable clothing, adaptive devices, and parenting is available through a national newsletter, seminars, and workshops.

Prevention of Secondary Complications

For issues related to the secondary complications that may arise in achondroplasia, see Treatment of Manifestations and Surveillance.


Guidelines for surveillance are incorporated into the American Academy of Pediatrics clinical report [Trotter et al 2005].

Growth. Monitor height and weight at each physician contact using growth curves standardized for achondroplasia [Horton et al 1978, Hoover-Fong et al 2007]

Development. Screening of developmental milestones throughout infancy and early childhood should be performed and compared with those specific for achondroplasia [Fowler et al 1997, Ireland et al 2010].

Head growth and risk for hydrocephalus

  • Complete baseline CT scan (or MRI) of the brain in infancy
  • Monitoring of head circumference using growth curves standardized for achondroplasia [Horton et al 1978] throughout childhood

Craniocervical junction

  • Every infant should have a CT scan (or MRI) of the craniocervical junction in infancy, with comparison of foramen magnum size to diagnostic-specific standards [Hecht et al 1989].
  • Overnight polysomnography should also be completed in infancy and interpreted with consideration of features important in assessing the craniocervical junction [Pauli et al 1995].
  • Neurologic examination including for signs of cervical myelopathy should be incorporated into each physical examination in infancy and childhood.

Sleep apnea

  • Inquiry should be made regarding signs and symptoms of sleep apnea.
  • If worrisome nighttime or daytime features arise, then polysomnography should be completed.

Ears and hearing

  • In addition to newborn screening, each infant should have tympanometric and behavioral audiometric evaluation by age approximately one year.
  • Evidence for middle ear problems or hearing loss should be sought throughout childhood.


  • The spine of the infant and child should be clinically assessed every six months until age three years.
  • If severe kyphosis appears to be developing, radiologic assessment is needed (lateral in sitting or standing, depending on age, and lateral cross-table prone or cross-table supine over a bolster).

Legs. Clinical assessment for development of bowing and/or internal tibial torsion should be part of each physical assessment.

Spinal stenosis. Because adults with achondroplasia are at increased risk for spinal stenosis, a clinical history and neurologic examination is warranted every three to five years once the person with achondroplasia reaches adulthood.

Adaptation to difference. Inquiry regarding social adjustment should be part of each primary physician contact.

Agents/Circumstances to Avoid

Particularly in childhood, care must be taken to limit risk for injury to the spinal cord at the craniocervical junction. This should include proscription of activities including collision sports (e.g., American football, ice hockey, rugby), use of a trampoline, diving from diving boards, vaulting in gymnastics, and hanging upside down from knees or feet on playground equipment.

Protocols have been published regarding positioning that should be avoided in order to decrease the likelihood of development of a fixed, angular kyphosis [Pauli et al 1997].

There is no increased risk for bone fragility or joint degeneration, and no circumstances to avoid related to these.

Evaluation of Relatives at Risk

See Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes.

Pregnancy Management

Cephalo-pelvic disproportion may necessitate delivery by caesarean section when the pregnant woman is of average stature and the fetus has achondroplasia.

Pregnant women with achondroplasia must always be delivered by caesarean section because of the small size of the pelvis.

Therapies Under Investigation

Search for access to information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder.

Genetic Counseling

Genetic counseling is the process of providing individuals and families with information on the nature, inheritance, and implications of genetic disorders to help them make informed medical and personal decisions. The following section deals with genetic risk assessment and the use of family history and genetic testing to clarify genetic status for family members. This section is not meant to address all personal, cultural, or ethical issues that individuals may face or to substitute for consultation with a genetics professional. —ED.

Mode of Inheritance

Achondroplasia is inherited in an autosomal dominant manner.

Risk to Family Members

Parents of a proband

  • Approximately 80% of individuals with achondroplasia have parents with average stature and have achondroplasia as a result of a de novo pathogenic variant.
  • De novo pathogenic variants are associated with advanced paternal age, often defined as older than age 35 years [Penrose 1955, Stoll et al 1982]. The de novo pathogenic variants causing achondroplasia are exclusively inherited from the father [Wilkin et al 1998].
  • The remaining 20% of individuals with achondroplasia have at least one affected parent.

Sibs of a proband

Offspring of a proband

  • The risk to offspring of an individual with achondroplasia of inheriting the mutated allele is 50%.
  • An individual with achondroplasia who has a partner with average stature has a 50% risk of having a child with achondroplasia.
  • When both parents have achondroplasia, their offspring have a 25% chance of having average stature; a 50% chance of having achondroplasia, and a 25% of having homozygous achondroplasia (a lethal condition).
  • Because many individuals with short stature have reproductive partners with short stature, offspring of individuals with achondroplasia may be at risk of having double heterozygosity for two dominantly inherited bone growth disorders. The phenotypes of these individuals may be distinct from those of the parents [Flynn & Pauli 2003]. When the proband and the proband's reproductive partner are affected with different dominantly inherited skeletal dysplasias, each child has a 25% risk of having average stature, a 25% risk of having the same skeletal dysplasia as the father, a 25% risk of having the same skeletal dysplasia as the mother, and a 25% risk of inheriting a pathogenic variant from both parents and being at risk for a potentially poor outcome.
    • Individuals who are compound heterozygotes for pathogenic variants causing hypochondroplasia and achondroplasia and in whom the hypochondroplasia results from the p.Asn540Lys pathogenic variant in FGFR3 have a severe skeletal phenotype and the potential for serious disability [McKusick et al 1973, Sommer et al 1987, Huggins et al 1999]. Individuals who are double heterozygotes for pathogenic variants at two different loci (FGFR3 and non-FGFR3) have less marked phenotypic abnormalities [Flynn & Pauli 2003].
    • Poor outcomes have been reported for individuals who are double heterozygotes for achondroplasia and spondyloepiphyseal dysplasia congenita [Young et al 1992, Günthard et al 1995, Flynn & Pauli 2003] or achondroplasia and pseudoachondroplasia [Langer et al 1993]. Individuals who are double heterozygotes for achondroplasia and spondyloepiphyseal dysplasia congenita or achondroplasia and pseudoachondroplasia tend to have additional physical characteristics, radiographic findings, and clinically relevant sequelae.
    • Double heterozygotes for achondroplasia and dyschondrosteosis (see SHOX-Related Haploinsufficiency Disorders) or hypochondroplasia and dyschondrosteosis have phenotypes that do not appear to be more severe than that of either parent [Ross et al 2003]. In fact, double heterozygosity for achondroplasia and dyschondrosteosis seems to result in an ameliorating effect for certain findings (macrocephaly, stature, tibial foreshortening)

Other family members of a proband. The risk to other family members depends on the status of the proband's parents. If a parent is affected, his or her family members are at risk.

Related Genetic Counseling Issues

Considerations in families with an apparent de novo pathogenic variant. When neither parent of a proband with an autosomal dominant condition has clinical evidence of the disorder, it is likely that the proband has a de novo pathogenic variant. However, possible non-medical explanations including alternate paternity or maternity (e.g., with assisted reproduction) or undisclosed adoption could also be explored.

Family planning

  • The optimal time for determination of genetic risk and discussion of the availability of prenatal testing is before pregnancy.
  • It is appropriate to offer genetic counseling (including discussion of potential risks to offspring and reproductive options) to young adults who are affected.

DNA banking is the storage of DNA (typically extracted from white blood cells) for possible future use. Because it is likely that testing methodology and our understanding of genes, allelic variants, and diseases will improve in the future, consideration should be given to banking DNA of affected individuals.

Prenatal Testing

High-risk pregnancy. A high-risk pregnancy is one in which one or both parents have achondroplasia. Prenatal diagnosis for high-risk pregnancies is possible by analysis of DNA extracted from fetal cells obtained by amniocentesis usually performed at about 15 to 18 weeks' gestation or chorionic villus sampling (CVS) at about ten to 12 weeks' gestation [Bellus et al 1994, Shiang et al 1994]. The disease-causing allele in the affected parent or parents must be identified before prenatal testing can be performed.

Note: Gestational age is expressed as menstrual weeks calculated either from the first day of the last normal menstrual period or by ultrasound measurements.

Low-risk pregnancy. Routine prenatal ultrasound examination may identify short fetal limbs and raise the possibility of achondroplasia in a fetus not known to be at increased risk.

Krakow et al [2003] describe the use of 3D ultrasonography in pregnancies from 16 to 28 weeks' gestation to enhance appreciation of the facial features and relative proportions of the appendicular skeleton and limbs. Ruano et al [2004] used a combination of 3D ultrasonography and intrauterine 3D helical computer tomography (3D HCT) to enhance the diagnostic accuracy for intrauterine skeletal dysplasias, and Chitty et al [2011] published the frequency of various ultrasonographic features in fetuses with achondroplasia.

DNA extracted from fetal cells obtained by amniocentesis can be analyzed for FGFR3 pathogenic variants if achondroplasia is suspected. Preliminary evidence suggests that diagnosis may also be possible by detection of the FGFR3 pathogenic variant in fetal DNA in maternal serum [Chitty et al 2011, Lim et al 2011].

Preimplantation genetic diagnosis (PGD) may be an option for some families in which the pathogenic variant has been identified.


GeneReviews staff has selected the following disease-specific and/or umbrella support organizations and/or registries for the benefit of individuals with this disorder and their families. GeneReviews is not responsible for the information provided by other organizations. For information on selection criteria, click here.

  • My46 Trait Profile
  • National Library of Medicine Genetics Home Reference
  • NCBI Genes and Disease
  • Child Growth Foundation
    United Kingdom
  • Human Growth Foundation (HGF)
    997 Glen Cove Avenue
    Suite 5
    Glen Head NY 11545
    Phone: 800-451-6434 (toll-free)
    Fax: 516-671-4055
  • Little People of America, Inc. (LPA)
    250 El Camino Real
    Suite 201
    Tustin CA 92780
    Phone: 888-572-2001 (toll-free); 714-368-3689
    Fax: 714-368-3367
  • MAGIC Foundation
    6645 West North Avenue
    Oak Park IL 60302
    Phone: 800-362-4423 (Toll-free Parent Help Line); 708-383-0808
    Fax: 708-383-0899
  • Medline Plus
  • International Skeletal Dysplasia Registry
    615 Charles E. Young Drive
    South Room 410
    Los Angeles CA 90095-7358
    Phone: 310-825-8998

Molecular Genetics

Information in the Molecular Genetics and OMIM tables may differ from that elsewhere in the GeneReview: tables may contain more recent information. —ED.

Table A.

Achondroplasia: Genes and Databases

GeneChromosome LocusProteinLocus SpecificHGMD
FGFR34p16​.3Fibroblast growth factor receptor 3FGFR3 @ LOVDFGFR3

Data are compiled from the following standard references: gene from HGNC; chromosome locus, locus name, critical region, complementation group from OMIM; protein from UniProt. For a description of databases (Locus Specific, HGMD) to which links are provided, click here.

Table B.

OMIM Entries for Achondroplasia (View All in OMIM)


Gene structure. The 4.3-kb cDNA has 19 exons and encodes an 806-residue protein (isoform 1).

Pathogenic variants. More than 99% of individuals with achondroplasia have one of two pathogenic variants in FGFR3. Two different substitutions at nucleotide 1138 both result in the amino acid change p.Gly380Arg (Table 2). Several exceptions with pathogenic variants at other nucleotides have been reported. (For more information, see Table A, HGMD.)

Table 2.

Selected FGFR3 Pathogenic Variants in Achondroplasia

DNA Nucleotide ChangePredicted Protein ChangeReference Sequences

Note on variant classification: Variants listed in the table have been provided by the author. GeneReviews staff have not independently verified the classification of variants.

Note on nomenclature: GeneReviews follows the standard naming conventions of the Human Genome Variation Society (www​ See Quick Reference for an explanation of nomenclature.

Normal gene product. Fibroblast growth factor receptor 3. The mature FGFR3 protein, like all of the FGFRs, is a membrane-spanning tyrosine kinase receptor with an extracellular ligand-binding domain consisting of three immunoglobulin (Ig) subdomains, a transmembrane domain, and a split intracellular tyrosine kinase domain [Laederich & Horton 2010]. Alternative splice sites in the FGFR genes result in tissue-specific isoforms [Chellaiah et al 1994].

FGFR3 is activated by various fibroblast growth factors (FGFs) [Ornitz 2005]. Binding appears to result in receptor dimerization, transactivation of tyrosine kinase and transphosphorylation of tyrosine residues [Plotnikov et al 1999] These modifications result in activation of a number of downstream signaling pathways, including signal transducer and activator of transcription (STAT) and mitogen-activated protein kinase (MAPK) [Deng et al 1996, Eswarakumar et al 2005]. Overall, these secondary pathways cause slowing of proliferation and differentiation of chondrocytes [Dailey et al 2003].

Abnormal gene product. The p.Gly380Arg pathogenic variant resulting in achondroplasia causes constitutive activation of FGFR3, which is, through its inhibition of chondrocyte proliferation and differentiation, a negative regulator of bone growth [Horton & Degnin 2009]. Indeed, the members of the family of bone dysplasias that includes hypochondroplasia, achondroplasia, SADDAN dysplasia, and thanatophoric dysplasia type I and II [Spranger 1985] are the result of allelic FGFR3 pathogenic variants that result in a graded series of FGFR3 activation [Naski et al 1996, Vajo et al 2000]. Although the precise consequences of the achondroplasia-causing variant in FGFR3 are still uncertain, the net result is excess inhibitory signaling in growth plate chrondrocytes [Ornitz 2005], principally, it appears, through the MAPK pathway [Zhang et al 2006]. A variety of therapeutic approaches are suggested by current understanding of FGFs, FGFRs, MAPK, and proteins interacting with the MAPK pathway, such as C-type natriuretic peptide [Yasoda et al 2004, Kake et al 2009, Laederich & Horton 2010].


Literature Cited

  • Ain MC, Browne JA. Spinal arthrodesis with instrumentation for thoracolumbar kyphosis in pediatric achondroplasia. Spine. 2004;29:2075–80. [PubMed: 15371713]
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Chapter Notes

Author History

Clair A Francomano, MD; National Institutes of Health (1998-2012)
Richard M Pauli, MD, PhD (2012-present)
Douglas J Wilkin, PhD; Federal Bureau of Investigation (1998-2001)

Revision History

  • 16 February 2012 (me) Comprehensive update posted live
  • 9 January 2006 (me) Comprehensive update posted to live Web site
  • 31 July 2003 (me) Comprehensive update posted to live Web site
  • 8 March 2001 (me) Comprehensive update posted to live Web site
  • 12 October 1998 (pb) Review posted to live Web site
  • 26 June 1998 (cf) Original submission
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