eMedicine Specialties > Orthopedic Surgery > Pediatrics

Achondroplasia

Author: Shital Parikh, MBBS, MS, Consulting Staff, Department of Orthopedics, Buchanan General Hospital
Coauthor(s): Preeti Batra, MBBS, MD, Staff Physician, Department of Radiology, VS Hospital, India
Contributor Information and Disclosures

Updated: Jan 26, 2009

Introduction

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.¹ 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 1878.² 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.^3,4,5

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.⁶
  • 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)¹
  • Obstructive and restrictive respiratory complications (eg, upper airway obstruction, pneumonia, apnea)
  • Hydrocephalus
  • Spinal deformities (eg, kyphosis, lordosis, scoliosis)
  • Obesity^7,8
  • 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.)

Clinical

History

• Gross motor development frequently is delayed. Motor milestones such as head control and independent sitting, standing, and ambulation may lag by 3-6 months. Speech and language problems may be caused by tongue thrust (due to abnormal maxillomandibular relationship) but often resolve spontaneously. Twenty percent of patients experience delayed speech acquisition. Cognitive skills are preserved, and the intelligence level is within normal limits. Cranial enlargement and poor head control place the infant at risk for extension injuries.
• Standing height is below the third percentile for both sexes. The mean adult standing height for men is 132 cm (52 in), and that for women is 125 cm (49 in). Sitting height, a reflection of trunk length, is within normal limits.
• Seventy-five percent of patients have otitis media when younger than 5 years. Recurrent otitis media is common due to poor drainage of the eustachian tubes from underdevelopment of the midface, relative hypertrophy of tonsils and adenoids, and temporal bone abnormalities. Conductive hearing loss is present due to ossicular chain stiffness, and may be either congenital or acquired due to recurrent otitis media. Sensorineural hearing loss may be present in a few patients. Maxillary hypoplasia may lead to dental crowding and malocclusion.
• Upper airway obstruction, small chest wall, pectus excavatum, and neurogenic effects from brain stem compression reduce the vital capacity. Incidence of pneumonia, cyanotic spells, apnea, and other respiratory complications is increased. Symptoms of airway obstruction include snoring and sleeping with the neck in a hyperextended position.
• Abnormal development of the base of the skull results in a foramen magnum that is smaller than in average individuals. Narrowing of the foramen magnum compresses the cervicomedullary region, causing symptoms of respiratory insufficiency, apnea, cyanotic episodes, feeding problems, quadriparesis, and sudden death. These symptoms are common in the first several years of life because of the failure of the anticipated enlargement of foramen magnum during infancy and childhood. Chronic brain stem compression also may be a cause of hypotonia observed in the first 2 years of life.
• Stenosis of the spinal canal and intervertebral foramen leads to symptoms such as low back pain, leg pain, dysesthesia, paresthesia, paraparesis, incontinence, and neurogenic claudication. Claudication may present as vague symptoms of aching or tiredness of the lower extremities induced by walking or standing. Symptoms may progress with a sensation of tingling and numbness and, eventually, weakness. Often, the pain is alleviated if the patient assumes a squatting position or bends forward.
• More than 50% of patients experience symptoms of lower extremity radiculopathy from nerve root compression or cauda equina syndrome. The mean age of onset of back or lower extremity symptoms is 26 years; one third of patients are younger than 15 years at onset.
• Symptoms due to abnormal curvature of the spine (eg, kyphosis, lordosis, scoliosis) may be present, such as deformity, back pain, respiratory dysfunction, neurologic involvement, or symptoms of spinal stenosis. The incidence of kyphoscoliosis may be as high as 33-50% in adults. However, the curve magnitude is generally less than 30° and generally does not require treatment.
• Joint laxity may be present in children. Genu recurvatum is common. As the child grows, genu varum (tibial bowing) and lateral tibial torsion become apparent.
• Macrocephaly represents ventriculomegaly or arrested hydrocephalus.
• Mild but annoying neurologic disturbances can be attributed to local anatomic abnormalities and abnormal stretching of nerves. Examples include hip and knee pain from meralgia paresthetica, ankle pain from irritation of the peroneal nerve, or facial pain due to trigeminal neuralgia.
• Fibromyalgia (trigger points located in the lower part of the back) and trochanteric bursitis can be seen in some patients.

Physical

See Image 1.

• Achondroplasia is evident at birth as a disproportionate short-limb dwarfing condition. Characteristics include an enlarged neurocranium, frontal bossing, flattening of the nasal bridge, midface hypoplasia, and a relatively prominent mandible. The anteroposterior diameter of the chest is flattened, the lower ribs are flared, and the abdomen protrudes.
• Before walking, the child has a thoracolumbar kyphosis and lordosis in the interscapular thoracic region.⁹ The kyphosis can be severe in the sitting position and may not reduce completely in the prone position. Once independent ambulation is established, an exaggerated lumbar lordosis with forward rotation of the pelvis develops, and the spinal deformity is associated with hip flexion contractures and a prominent abdomen and buttocks. However, some degree of kyphosis persists in 25% of adults.
• The upper extremity involvement is rhizomelic, with the proximal segments more severely affected than the distal segments. The shoulders appear broad due to normal development of clavicle and well-developed musculature. The short arms may contribute to bulky muscle mass and apparent increased strength in such individuals. Loss of full extension of the elbow, ranging from 15-30°, is present. A trident hand is common and is characterized by a persistent space between the long and ring fingers when approximation of the fingers is attempted in full extension. The fingertips reach the level of the hips, which causes difficulty with hygiene and dressing.
• Lower extremity involvement is rhizomelic, with hip flexion contractures, ligamentous laxity and external rotation of the extremity, and genu recurvatum before walking age. The tibia is bowed, resulting in significant genu varum and some degree of ankle varus. Frequently, gaping of the lateral compartment or lateral translation of the tibia on the femur can be seen during the stance phase. Occasionally, a valgus deformity may develop. The gait is usually a waddling gait, and circumduction motion of the hips and lower extremities occurs when running is attempted.
• Spinal deformities are the most common and potentially disabling problems.^10,11,12 Spinal canal stenosis and stenosis of the intervertebral foramen are secondary to short thickened pedicles, interpedicular narrowing, thickened laminae, intervertebral disc herniation, degenerative spondylolysis, excessive lumbar lordosis, or anterior wedging of the vertebral bodies from thoracolumbar kyphosis. Sensory deficits, posterior column dysfunction, lower and upper motor neuron signs, and signs of neurologic claudication may be present. Signs of lower extremity radiculopathy from nerve root compression or cauda equina syndrome are present in more than 50% of patients.
• Macrocephaly is present due to triventricular enlargement and hydrocephalus.¹³ However, intracranial pressure is not elevated significantly. In infants, a rough estimate of the pressure can be made by palpating the fontanelles.

Causes

• Genetic basis for achondroplasia¹⁴
  • A single gene mapped to the short arm of the fourth chromosome (band 4p16.3) is responsible for achondroplasia and is transmitted as an autosomal dominant trait.
  • At least 80% of cases result from a random new mutation. In sporadic cases, a paternal age older than 36 years is common. Most parents are of average size and have no family history of a dwarfing condition. The risk of the parents producing a second affected child is almost negligible. Reports have estimated that there is a 1 in 443 risk of recurrence of achondroplasia in the siblings of an affected child with unaffected parents. This is because of gonadal mosaicism in the parents. Average-sized siblings have no increased risk of producing a child with achondroplasia. When both parents have achondroplasia, 50% of their offspring are heterozygous and affected, 25% are homozygous, which is ordinarily fatal in the first few months of life, and 25% are unaffected. When one parent has achondroplasia, the chance of transmitting this gene to each child is 50%.
• Molecular basis of achondroplasia
  • Fibroblast growth factors are structurally related proteins associated with cell growth, migration, wound healing, and angiogenesis. At the cellular level, their function is mediated by transmembrane tyrosine kinase receptors, known as fibroblast growth factor receptors (FGFR).¹⁵
  • Mutation in FGFR3 is responsible for achondroplasia, hypochondroplasia, and thanatophoric dysplasia.¹⁵ The primary function of FGFR3 is to limit osteogenesis. Mutation causes enhancement in its function of limiting endochondral ossification. Mutation in FGFR3 in achondroplasia is due to transition of guanine to adenine (G to A) at nucleotide 1138 of complimentary DNA.
• Two reports exist of achondroplasia associated with Down syndrome.¹⁶ The calculated risk of association is 1 case in every 8 years in the United States, based on the current birth rate.

• Search for CME/CE on This Topic »

• Achondroplasia (Radiology)
• Achondroplasia (Pediatrics: Genetics and Metabolic Disease)
• Skeletal Dysplasia (Pediatrics: Genetics and Metabolic Disease)
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