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Thursday, Oct 02nd

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Diagnosis

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Achondroplasia may be suspected based on late prenatal ultrasound images or by clinical findings at birth. The diagnosis can typically be made based on physical exam and radiographic findings shortly after birth. Genetic testing is available in a prenatal or postnatal setting.

Diagnostic Testing and Evaluation

Diagnostic Criteria

  • Diagnosis is confirmed with classical physical and radiographic findings  (see chart above), including:
    • Short stature
    • Rhizomelic (proximal) shortening of the arms and legs with redundant skin folds on limbs
    • Limitation of elbow extension
    • Trident configuration of the hands
    • Genu varum (bow legs)
    • Thoracolumbar gibbus in infancy
    • Exaggerated lumbar lordosis, which develops when walking begins
    • Large head with frontal bossing
    • Midface hypoplasia
    • Narrowing of the interpediculate distance of the caudal spine
    • Notch-like sacroiliac groove
    • Circumflex or chevron seat on the metaphysis
  • Identification of one of two specific mutations in the FGFR3 gene confirms the diagnosis, but is not necessary.
  • Exclusionary features.  There are more than 200 skeletal dysplasias, including some caused by other mutations in the FGFR3 gene.  Alternative diagnosis should be considered when the following are noted:
    • Severely constricted or shortened thoracic cavity
    • Respiratory insufficiency in the newborn
    • Congenital fractures and brittle bones
    • Developmental delay in the absence of hydrocephalus or other neurologic compromise
    • Abnormal skin pigmentation such as acanthosis nigricans
    • Craniosynostosis
    • Cloverleaf skull shape
    • Cleft palate
    • Hearing loss

First Steps

  • Radiographic skeletal survey
  • Dysmorphology examination
  • In the prenatal setting, both of the above are accomplished via high resolution ultrasound after 16 weeks gestation
  • Family history assessment
    • Family history of "very short" stature or "dwarfism" should be confirmed with medical records of diagnosis or exam of affected individual(s). Management and reproductive risks will differ for other bone disorders and if short stature child is product of two parents with dwarfism.

Testing Strategy

  • Radiographic skeletal survey
  • Dysmorphology examination
  • family history assessment
  • For prenatal diagnosis, high resolution ultrasound exam at 16-28 weeks gestation for evaluation of bone length proportions. 
    • routine ultrasound prior to 16 weeks may not reveal typical features
    • Routine ultrasound examination after 16 weeks gestation may or may not reveal short limbs, disproportionate growth, or characteristic craniofacial features
    • ultrasound imaging ideally should be done at a center where technologist and physicians are specifically trained in looking for features of a dysplasia
    • 3D ultrasound may identify characteristic facial features
    • Fetal MRI or 3D HCT may improve diagnostic power
  • Molecular genetic testing is not usually indicated unless clinical findings are atypical, or for future reproductive planning

Tests that are NOT Helpful

  • Testing of unaffected parents is not indicated since most mutations are sporadic and fully penetrant.

Subsequent Evaluation

  • If achondroplasia suspected and molecular testing is desired, obtain targeted mutational analysis for the 2 common FGFR3 mutations
  • If other dysplasia is suspected, seek genetics consultation

Lifestyle/Environmental Contributors to Disease

  • Occurrence of new mutations in offspring has been associated with advanced paternal age.
  • No other environmental contributions to onset of condition, although environment can exacerbate secondary complications.

Differential Diagnosis

Achondroplasia is easily distinguished from other skeletal dysplasias by radiographic findings and physical features, but several other short stature skeletal dysplasias may have overlapping features:

  • Severe hypochondroplasia
  • SADDAN (severe achondroplasia, developmental delay, acanthosis nigricans)
  • Thanatophoric dysplasia
  • Pseudoachondroplasia:  features of pseudoachondroplasia do not present until 2 years of age; achondroplasia is obvious at or shortly after birth.

Diagnosis should always be confirmed, since management and reproductive risks are different for other causes of short stature

Consensus Statements and Guidelines

Trotter et al. American Academy of Pediatrics Clinical Report: Health Supervision for Children with Achondroplasia. Pediatrics. 2005; 116(3):771-783.