Achondroplasia is the most common form of short-limbed dwarfism and beside rhizomelic dwarfism includes macrocephaly, frontal bossing, low nasal bridge and midface hypoplasia, lumbar hyperlordosis, and/or stenosis of the spinal canal and hypotonia. Sleep-disordered breathing (obstructive sleep apnea) is common.
Achondroplasia has an incidence of approximately 4:100,000 births and about 80% of them appear to occur sporadically with no apparent family history.
However, the possibility of familial transmission has been suggested, and inheritance with new autosomal dominant gene mutations has been reported. Advanced paternal age may be a contributing factor in sporadic cases. In over 90% of cases, an autosomal dominant missense mutation (almost exclusively of paternal origin) is responsible for the disease and has been mapped to chromosome 4p16.3. Mutation analysis identified an arginine to glycine substitution at residue 380 in the fibroblast growth factor receptor 3 (FGFR-3), which affects the function of growth plate chondrocytes and results in inhibited cartilage proliferation and premature ossification of epiphyseal cartilage.
Achondroplasia is characterized by rhizomelic (ie, short humerus and femur) dwarfism with genua vara and bowing of the tibiae, macrocephaly, frontal bossing, and depressed nasal bridge. The dwarfism appearance with short arms and legs and a long trunk in comparison is further accentuated by the presence of scoliosis, thoracic kyphosis, lumbar hyperlordosis, and unusually prominent abdomen and buttocks. Shortening of the vertebral pedicles and narrowing of the lumbar interpedicular distance is common. Rib cage deformities including excessive curvature or “cupping” of the ribs may be present. In addition, chest circumference is often below the third percentile, particularly in children less than 2 years of age. The short, broad hands with brachydactyly usually form a characteristic “trident” or three-pronged position during extension. This trident position is assumed by index and middle finger close together and ring and fifth digit close together, giving the hand (with the thumb) the three-pronged (trident) appearance. Most joints are hyperextensible, but the range of motion in the elbows, hips, and temporomandibular joints may be limited. Infants typically have an arched or vaulted skull in response to megaloencephaly, which is pathognomonic for the syndrome. The forehead is broad and midface hypoplasia is common. Hydrocephalus may be present, thus the risk of elevated intracranial pressure (ICP) should be considered. Compression of the brainstem due to foramen magnum and cervical canal stenosis may occur in some children and result in life-threatening conditions. An increased incidence of obstructive sleep apnea has been reported due to midface hypoplasia with choanal stenosis, relative macroglossia, high-arched palate, decreased temporomandibular joint mobility, prominent mandible, short neck, and mild to moderate muscle hypotonia. Adenotonsillectomy may help improve these symptoms. In addition, central sleep apnea may be present due to the aforementioned brainstem compression, which, depending on the severity, may require suboccipital surgical decompression. The prognostic most ...