Achondroplasia is the most common form of inherited disproportionate short stature and is classified among the skeletal dysplasias known as chondrodysplasias. The condition is caused by pathogenic variants in FGFR3, located on chromosome 4, with the ClinGen consortium designating the gene-disease relationship as DEFINITIVE—the highest available evidence classification. Inheritance follows an autosomal dominant pattern. GeneReviews documents a prevalence of approximately 1 in 26,000–28,000 live births, establishing achondroplasia as the predominant inherited cause of disproportionate short stature. The clinical phenotype is recognizable at birth and frequently identifiable on prenatal imaging, given the characteristic skeletal findings. No distinct disease subtypes are documented in this packet; the features described represent the primary clinical entity.

Achondroplasia presents with a well-characterized constellation of obligate and high-frequency features spanning skeletal, respiratory, and growth domains. Features present in all affected individuals (HPO OBLIGATE) include short ribs, short femur, radial bowing, ulnar bowing, femoral bowing, flared metaphyses, severe platyspondyly, progressive narrowing of the vertebral interpedicular distance in the caudal direction, choanal stenosis, small foramen magnum, pulmonary hypoplasia, and respiratory distress. Feeding difficulties, polyhydramnios, and premature rupture of membranes are additional obligate features documented in the HPO record. Features documented at very high frequency (HPO VERY_FREQUENT) include disproportionate short stature, limb undergrowth, bowing of the legs, kyphosis, and thoracolumbar kyphosis. Frequently observed findings (HPO FREQUENT) include macrocephaly, frontal bossing, trident hand configuration, limited elbow extension, and floppy infant presentation in the newborn period. The small foramen magnum is a structurally significant obligate feature incorporated into GeneReviews surveillance protocols because of its potential neurological implications, including risks related to foramen magnum stenosis and brainstem compression.

Achondroplasia is caused by heterozygous pathogenic variants in FGFR3, the gene encoding fibroblast growth factor receptor 3, located on chromosome 4. The ClinGen consortium has classified the FGFR3–achondroplasia gene-disease relationship as DEFINITIVE, the highest evidence tier. Inheritance is autosomal dominant. GeneReviews documents complete penetrance: all individuals carrying an FGFR3 heterozygous pathogenic variant associated with achondroplasia express the full clinical manifestations of the disorder. GeneReviews notes that penetrance is 100%, making achondroplasia an autosomal dominant condition without documented reduced penetrance. No additional causative genes are certified in this packet.

GeneReviews describes a set of clinical and radiographic criteria used to establish the diagnosis of achondroplasia. The diagnosis is considered in newborns presenting with proximal shortening of the upper limbs, a large head with a prominent forehead, a narrow chest, and short digits in a trident configuration. Radiographic findings that confirm the diagnosis include square ilia and horizontal acetabula, a narrow sacrosciatic notch, proximal radiolucency of the femoral shafts, generalized metaphyseal abnormality with flaring, and caudally decreasing vertebral interpedicular distance in the lumbar spine. GeneReviews notes that in older individuals, clinical and radiographic features of achondroplasia are well-defined and distinguishable from the more than 700 recognized skeletal dysplasias, the majority of which have distinctive clinical or radiographic features distinguishing them from achondroplasia. The differential diagnosis includes hypochondroplasia, thanatophoric dysplasia, and other chondrodysplasias, which GeneReviews lists in a dedicated differential diagnosis section. Molecular confirmation via FGFR3 variant testing is available and can resolve ambiguous clinical presentations. This packet does not reference newborn screening for achondroplasia.

Vosoritide (VOXZOGO) received FDA approval for achondroplasia on November 19, 2021, under NDA designation and maintains ACTIVE market status. Vosoritide is the sole ACTIVE FDA-approved treatment certified in this packet. GeneReviews management guidance references health supervision guidelines established by the American Academy of Pediatrics Committee on Genetics, noting that these guidelines serve as general benchmarks and do not replace individualized clinical decision-making. GeneReviews also notes the existence of specialized skeletal dysplasia clinics whose specific protocols may vary from general guidelines. GeneReviews identifies a range of evaluations to be conducted following initial diagnosis, organized by clinical manifestation and covering neurological, musculoskeletal, and respiratory domains. Three compounds hold FDA orphan drug designation for achondroplasia without regulatory approval: an anti-fibroblast growth factor receptor 3 antigen-binding fragment (Genzyme, a Sanofi company); a C-type natriuretic peptide conjugated to a multi-arm polyethylene glycol carrier via a cleavable linker (Ascendis Pharma Growth Disorders); and infigratinib (QED Therapeutics, a BridgeBio company). Orphan drug designation indicates regulatory recognition of a condition's rarity and unmet medical need but does not constitute approval or establish clinical efficacy.

Natural history data is not certified in this packet. GeneReviews describes a surveillance framework incorporating periodic assessments at minimum every six months during infancy and toddlerhood, annually through childhood, and every five years in adulthood, as outlined in the American Academy of Pediatrics health supervision guidelines. The framework addresses neurological concerns associated with the foramen magnum and foramen magnum stenosis, which GeneReviews identifies as a relevant clinical concern given the small foramen magnum documented as an obligate feature. Surveillance also addresses musculoskeletal manifestations including kyphosis and thoracolumbar kyphosis, as well as respiratory considerations. Pulmonary hypoplasia and respiratory distress are documented as obligate features in the HPO phenotype record, and GeneReviews management guidance incorporates respiratory evaluation following initial diagnosis.

Multiple interventional clinical trials are actively enrolling. BEACH301 (NCT06842355), a Phase 2 study of TYRA-300 in children with achondroplasia sponsored by Tyra Biosciences, began enrollment in March 2025 with an estimated completion date of June 2030. A Phase 2 head-to-head study (NCT07441876) comparing BMN 333 against vosoritide in children with achondroplasia, sponsored by BioMarin Pharmaceutical, opened in April 2026 with a planned completion of September 2029. An interventional Phase 2 study of infigratinib in children under three years of age with achondroplasia (NCT07169279), sponsored by QED Therapeutics, began recruiting in November 2025 with completion expected in March 2032. VISTA (NCT06168201), a virtual observational study of achondroplasia sponsored by BioMarin Pharmaceutical, has been enrolling since February 2023 with an estimated completion of February 2028.