History
Achondroplasia is primarily due to a de novo mutational event; however, there may be parents of an affected child who are affected themselves and are heterozygous for either the G1138A or G1138C mutation. Identifying family members at risk aids in addressing medical treatment plans, offering genetic counseling with options for genetic testing, and providing educational materials and emotional support.
Once the diagnosis of achondroplasia is made, obtain the following history to avoid serious complications:
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A history of lower back numbness or pain, apnea, ataxia, and incontinence may be due to cervicomedullary compression. Cord compression can lead to respiratory arrest and progressive quadriparesis. Surgical indicators to release this compression include a small foramen magnum, central hypopnea, and brisk reflexes.
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Obtain a careful history for recurrent otitis media to prevent conductive hearing loss, a factor related to speech delay.
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A history of sleep disturbances [21] and increased head size may indicate neurologic and respiratory complications.
Physical
Neurologic findings are as follows:
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Hypotonia in infancy and early childhood
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Delayed motor milestones
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Normal intelligence with possible minor deficits in visual-spatial tasks
Craniofacial features are as follows:
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Large calvarial bones in contrast to the small cranial base and facial bones
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True megalencephaly (large head) with frontal bossing
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Midface hypoplasia
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Dental malocclusion and crowding
Skeletal features are as follows:
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Disproportionate short stature: Male average adult height 131 ± 5.6 cm; female average adult height 124 ± 5.9 cm; average adult height for both approximately 4 feet
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Normal trunk length that appears long and narrow
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Small thoracic cage
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Rhizomelic shortening of the proximal limbs (arms and legs) with redundant skin folds
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Brachydactyly
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Trident hand configuration: Marked separation between the ring and middle fingers, giving the hand a 3-pronged appearance
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Thoracolumbar gibbus (lumbar kyphosis) in infancy, which is replaced by an exaggerated lumbar lordosis once ambulation begins
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Hyperextensibility of joints, especially the knee joint
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Limited elbow extension and rotation
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Genu varum (bowed legs)
In a study of adult males with achondroplasia, Sims et al found the patellar tendons to be more compliant in these individuals than in controls; the investigators suggested this to be a factor behind lower relative knee extensor force production seen in achondroplasia. The investigators reported a 47% reduction in stiffness and a 51% lower Young’s modulus, in achondroplastic patellar tendons, with the stress produced through isometric maximal voluntary contraction (iMVC) in subjects with achondroplasia being 54% below that of controls. In addition, the achondroplastic patellar tendons demonstrated 22% less maximal excursion at iMVC than did the controls’ tendons. [22]
Causes
Advanced paternal age (> 35 y) is identified as a risk factor for de novo cases of autosomal dominant syndromes. Achondroplasia is part of this category and suggests that factors influencing DNA replication or repair during spermatogenesis may predispose to the occurrence of G1138A or G1138C FGFR3 mutations in older men.
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Height for females with achondroplasia (mean/standard deviation [SD]) compared to normal standard curves. The graph is based on information from 214 females. Adapted from Horton WA, Rotter JI, Rimoin DL, et al. Standard growth curves for achondroplasia. J Pediatr. 1978 Sep; 93(3): 435-8.
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Height for males with achondroplasia (mean/2 standard deviations [SDs]) compared to normal standard curves. The graph is based on information from 189 males. Adapted from Horton WA, Rotter JI, Rimoin DL, et al: Standard growth curves for achondroplasia. J Pediatr. 1978 Sep; 93(3): 435-8.
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Mean growth velocities (solid line) for males (top) and females (bottom) with achondroplasia compared to normal growth velocity curves. Dashed lines indicate third percentile, mean, and 97th percentile. Data are from 26 males and 35 females. Adapted from Horton WA, Rotter JI, Rimoin DL, et al. Standard growth curves for achondroplasia. J Pediatr. 1978 Sep; 93(3): 435-8.
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Upper and lower segment lengths for males (top) and (bottom) with achondroplasia (mean/standard deviation [SD]). Data are from 75 males and 95 females. Adapted from Horton WA, Rotter JI, Rimoin DL, et al. Standard growth curves for achondroplasia. J Pediatr. 1978 Sep; 93(3): 435-8.
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Head circumference for females with achondroplasia compared to normal curves (dashed lines). Data are from 145 females. Adapted from Horton WA, Rotter JI, Rimoin DL, et al. Standard growth curves for achondroplasia. J Pediatr. 1978 Sep; 93(3): 435-8.
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Head circumference for males with achondroplasia compared to normal curves (dashed lines). Data are from 114 females. Adapted from Horton WA, Rotter JI, Rimoin DL, et al. Standard growth curves for achondroplasia. J Pediatr. 1978 Sep; 93(3): 435-8.
