Achondroplasia

Achondroplasia is the most common form of genetically determined disproportionate short stature. It is a form of dwarfism with short limbs. Achondroplasia literally means “a condition without cartilage” — however, the problem is not underdeveloped cartilage but the process of ossification, the transformation of cartilage into bone during development, especially in the long bones of the limbs.
It occurs in approximately one out of 15,000 newborns, although different sources provide different figures, commonly ranging from 1 in 10,000 to 1 in 40,000. This genetic disorder is caused by a mutation in the FGFR3 gene, which encodes the receptor for fibroblast growth factors.

Achondroplasia is an autosomal dominant disorder. About 80% of individuals with achondroplasia have parents of normal stature; the occurrence of achondroplasia is the result of a de novo mutation (not present in the parents). Such parents have a very low chance of having another child with achondroplasia. An individual with achondroplasia who has a partner of normal stature has a 50% risk during each pregnancy of having a child with achondroplasia.

If both parents have achondroplasia, the probabilities are:

• 25% chance of having a healthy child
• 50% chance of having a child with achondroplasia (one affected allele and one healthy allele)
• 25% chance of having a child with homozygous achondroplasia, which is incompatible with life

Symptoms

Achondroplasia is characterized by abnormal bone growth, which manifests as short stature with disproportionately short arms and legs, average trunk size, a large head (macrocephaly), and characteristic facial features, including a prominent forehead and underdeveloped nasal bridge.
In childhood, low muscle tone is typical and psychomotor development is usually delayed. Intellectual ability is not affected.

Life expectancy is not shortened, but frequent and life‑threatening conditions may occur in childhood due to episodes of apnea (slowed or paused breathing in early childhood).
Common problems include recurrent ear infections, obesity, kyphosis and lordosis of the spine, and resulting back pain.

Average adult height:

• men: 131 ± 5 cm
• women: 124 ± 6 cm

Diagnosis

Achondroplasia can be diagnosed based on characteristic clinical and radiographic findings in most individuals. For individuals who are too young for diagnosis or who have atypical findings, molecular genetic testing for the FGFR3 mutation should be used.
Confirmation by molecular genetics has 99% accuracy.

Treatment

For children with achondroplasia, it is recommended to monitor height, weight, and head circumference; manage weight to prevent obesity; and perform MRI or CT to evaluate signs of spinal canal stenosis. Surgical removal of adenoids or tonsils may be necessary; CPAP can be used as prevention of apnea syndrome; and tracheostomy may be indicated to manage obstructive sleep apnea. Suboccipital decompression is performed when hyperreflexia of the lower limbs, clonic spasms, breathing difficulties, or hypopnea are present. Support in socialization and adaptation in school is also important.

• enlarged head in newborns — macrocephaly (represents a risk of intracranial bleeding during vaginal delivery)
• obesity is a major problem in individuals with achondroplasia — excessive weight gain appears in early childhood (until a height of 75 cm is reached, height‑to‑weight ratios in children with achondroplasia are nearly identical to those of other children; after surpassing this height, the height–weight ratio begins to differ)
• hypotonic syndrome in children
• delayed psychomotor development
• in adulthood, obesity may contribute to lumbar stenosis and lead to various joint problems, and later may also contribute to early mortality associated with cardiovascular complications
• short stature — men: 131 ± 5 cm; women: 124 ± 6 cm
• shorter arms and legs with redundant skin folds on the limbs
• limited elbow extension (difficulty fully straightening the elbow)
• trident hand configuration (trident-shaped spacing of the fingers)
• lumbar lordosis (excessive inward curvature of the lower spine)
• prominent abdomen when standing due to lumbar hyperlordosis
• congenital or acquired characteristic positioning of the knees
• bow‑legged appearance (genu varum, “legs in an O‑shape”)
• thoracolumbar gibbus (spinal hump) in childhood
• excessive backward curvature of the spine during early walking
• large head with frontal rounding
• underdeveloped nasal bridge
• joint instability