Excerpt from Achondroplasia

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Background

The skeletal dysplasias are a heterogeneous group of disorders characterized by intrinsic abnormalities in the growth and/or remodeling of cartilage and bone. These dysplasias affect the skull, spine, and extremities in varying degrees. They frequently cause a disproportionately short stature (dwarfism); the standing height falls below the third percentile for age. Achondroplasia is the most common type of short-limb disproportionate dwarfism. The term achondroplasia, implying absent cartilage formation, was first used by Parrot in 1878.¹ Although the word achondroplasia is inaccurate from a histopathologic perspective, its use is universal and accepted by the International Working Group on Constitutional Diseases of the Bone.^{2, 3}

(See also the eMedicine articles Developmental Dysplasia of the Hip, Diastrophic Dysplasia, Multiple Epiphyseal Dysplasia, and Osteofibrous Dysplasia, as well as the articles Thoracolumbar Spinal Deformity in Achondroplasia and Skeletal Dysplasia Involving the Subaxial Cervical Spine, on Medscape.)

Pathophysiology

Dwarfing conditions are frequently referred to as short-limb or short-trunk types, according to whether the trunk or limbs are more extensively involved. Achondroplasia, hypochondroplasia, and metaphyseal chondrodysplasias are considered short-limb dwarfing conditions. These patients' sitting height is within normal range. Additional terms used to describe the segment of the limb with the greatest involvement are rhizomelic (proximal), mesomelic (middle), and acromelic (distal). In achondroplasia, the extremity involvement is rhizomelic, with the arms and thighs more severely involved than the forearms, legs, hands, and feet.

The primary defect found in patients with achondroplasia is abnormal endochondral ossification. Periosteal and intramembranous ossification is normal. Tubular bones are short and broad, reflecting normal periosteal growth. The iliac crest apophyses (appositional growth) are normal, giving rise to large, square iliac wings. The growth of the triradiate cartilage (endochondral growth) is abnormal, giving rise to horizontal acetabular roofs. Thus, these patterns of defect help to explain many of the observed clinical and radiographic characteristics of achondroplasia.

The characteristic features of achondroplasia are apparent at birth. Diagnosis is made based on physical examination and skeletal radiographic findings.

Frequency

United States

Approximately 10,000 individuals are estimated to have achondroplasia in the United States.

International

Achondroplasia affects about 1 in every 40,000 children. (This number varies, depending on the source.) Eighty percent of all "little people" have achondroplasia. Approximately 150,000 persons have achondroplasia worldwide. The worldwide population of little people is approximately 190,000.

Mortality/Morbidity

• The standardized mortality ratio is increased for all age groups by a factor of 2.27 over that of the general population.⁴
  • In children younger than 4 years, death most commonly occurs due to brain stem compression, which causes sudden death.
  • In individuals aged 5-24 years, central nervous system and respiratory abnormalities are the common causes of death.
  • In persons aged 25-54 years, cardiovascular problems are the most frequent causes of death.
• Morbidity associated with achondroplasia may include the following:
  • Recurrent otitis media (hearing loss)
  • Neurologic complications due to cervicomedullary compression (eg, hypotonia, respiratory insufficiency, apnea, cyanotic episodes, feeding problems, quadriparesis, sudden death)
  • Obstructive and restrictive respiratory complications (eg, upper airway obstruction, pneumonia, apnea)
  • Hydrocephalus
  • Spinal deformities (eg, kyphosis, lordosis, scoliosis)
  • Obesity
  • Spinal canal stenosis
  • Genu varum
  • Cardiovascular complications

Race

Achondroplasia occurs in all the races with equal frequency.

Sex

Achondroplasia occurs with equal frequency in males and females. (It is inherited in an autosomal dominant manner.)

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