4 Achondroplasia
Chondrodystrophia fetalis, Chondrodysplasia fetalis, chondrodystrophic dwarfism, ACH
Short stature, short limbs (rhizomelic), large head, prominent forehead, midface hypoplasia, lumbar lor- dosis, genu varum, ‘trident’ hands
Frequency: 1 in 26,000–66,000 births; M<F.
Genetics
Autosomal dominant (OMIM 100800) with complete penetrance; 7/8 cases new mutations; paternal age ef- fect; due to mutation in the FGFR3 (fibroblast growth factor receptor-3, OMIM 134934) gene mapped to 4p16.3; more than 98% of mutations are G-to-A tran- sition or G-to-A transversion at nucleotide 1138; ho- mozygous ACH found in 1/4 of sibs born to heterozy- gous parents; allelic mutations: hypochrondroplasia, thanatophoric dysplasia.
Clinical Features
• Rhizomelic dwarfism identifiable at birth
• Characteristic facies (large head, prominent fore- head, midface hypoplasia, low nasal bridge)
• Trident hands
• Relative prognathism
• Protuberant abdomen
• Lumbar lordosis
• Rolling gait from backward tilt of pelvis and hip joints
Complications
Hydrocephalus, spinal cord compression, syringo- myelia, recurrent ear infections, dental malocclusion
Differential Diagnosis
• Hypochondroplasia
• Pseudoachondroplasia
Radiographic Features Skull
• Large calvarium, frontal bossing
• Shortened skull base, small foramen magnum (possibly resulting in communicating hydro- cephalus)
• Broad mandible
Extremities
• Shortening of long bones, mostly of humeri and femurs (rhizomelia)
• Fibular lengthening (high position of fibular head)
• Limb bowing
• Oval lucent appearance of proximal femurs and humeri (in infancy)
• V-shaped metaphyses with ‘ball-in-socket’epiphy- ses
• Short ulna
• Brachydactyly, trident hand (uniform length of short bones, with divergent fingers)
Pelvis
• Squared, flat pelvic bones
• Flattened iliac wings
• Horizontal acetabula
• Small sacroiliac notches
Fig. 4.1. Patient 1, age 2 months. Note rhizomelic dwarfism, large head with prominent forehead, midface hypoplasia, low nasal bridge, relatively long trunk with narrow chest and pro- tuberant abdomen. Also note small hands and feet, and inca- pability of full extension at the elbows
Achondroplasia 583
A
Fig. 4.2 a, b. Patient 2, age 6 years.
Dwarfism of the rhizomelic type (humeri and femurs mostly in- volved), large head with frontal bossing, narrow chest, protuber- ant abdomen, thoracic kyphosis, lumbar hyperlordosis, and back- ward tilting of pelvis
a b
a
b
Fig. 4.3 a, b. Two newborns. a Patient 3; b patient 4. In each case, the calvarium is large with prominent frontal bones, the skull base is shortened, and the facial bones are relatively hypoplastic, while the mandible is broad and prognathic
Spine
• Narrowed lumbar spinal canal
• Progressive craniocaudal interpediculate narrow- ing
• Bullet-shaped vertebrae in infancy and early childhood
• Anterior beaking of vertebrae of upper lumbar spine
• Short vertebral pedicles
• Posterior vertebral scalloping
• Wide intervertebral foramina
• Thoracolumbar kyphosis (gibbus) + sacral lordosis Chest
• Squaring of inferior scapular margin
• Narrow chest with short ribs
Bibliography
Bellus GA, Hefferon TW, Ortiz de Luna RI, Hecht JT, Horton WA, Machado M, Kaitilia I, McIntosh I, Francomano CA.
Achondroplasia is defined by recurrent G830R mutations of FGFR3. Am J Hum Genet 1995; 56: 368–73
Hunter AG, Bankier A, Rogers JG, Sillence D, Scott CI Jr. Med- ical complications of achondroplasia: a multicentre patient review. J Med Genet 1998; 35: 705–12
Langer LO Jr, Baumann PA, Gorlin RJ. Achondroplasia. AJR Am J Roentgenol 1967; 100: 12–26
Nicoletti B, Kopits SE, Ascani E, McKusick VA (eds.). Human achondroplasia: a multidisciplinary approach. Plenum Press, New York, 1988
Oberklaid F, Danks DM, Jensen F, Stace L, Rosshandler S.
Achondroplasia and hyperchondroplasia: comments on frequency, mutation rate, and radiological features in skull and spine. J Med Genet 1979; 16: 140–6
Sommer A, Young-Wee T, Frye T. Achondroplasia-hypochon- droplasia complex. Am J Med Genet 1987; 26: 949–57 Fig. 4.4. aPatient 5, age 3 months. Note vertebral flattening, with increased height of the intervertebral spaces, dorsal scalloping of vertebral bodies, short pedicles, and increased angulation at the lumbosacral junction. b, c Patient 3, age 7 years.
The interpediculate distance decreases from top to bottom (arrows). The lumbar vertebral canal is narrowed (b).Vertebrae of the upper lumbar spine are mildly flat anteriorly; those of the lower lumbar spine show posterior scalloping (arrows).
The pedicles are short (c) a
b c
Achondroplasia 585
A
Fig. 4.5 a–d. Four children. a Patient 6, age 4 months; b patient 4, newborn; c patient 3, age 4 years; d patient 3, age 7 years. The iliac bones are short and squared, with round external borders and horizontal acetabula. The sciatic notches are small. The ischial and pubic bones are broad and short, the proximal femurs appear as characteristic oval lucencies (a, b). The distal
ends of the femurs and proximal portions of the tibias are better ossified medially than laterally (b). The distal femoral metaphyses are V shaped, and corresponding epiphyses tend to be enclosed (ball-in-socket configuration) (c). c, d The femoral necks are short and wide. The sacrum articulates downward with the ilia (d)
a
b
c d
Fig. 4.6. Patient 3, age 7 years. In- verted V shape of the metaphyses at the knees, with ball-in-socket appearance of the distal femoral epiphyses. There is overgrowth of the proximal fibulas
Fig. 4.7 a, b. Two pediatric patients:
apatient 4, newborn; b patient 3, age 7 years. The tubular bones in the forearm are short, with wide and irregular metaphyses. The ra- dius is bowed and proximally defi- cient (b). The tubular bones in the hand are short. The proximal por- tions of the metacarpals are bul- bous and lucent (b)
a b
Achondroplasia 587
A
Fig. 4.8 a, b. Two infant patients:
apatient 4, newborn; b patient 6, 4 months. Marked shortening of the tubular bones in the hands, with fingers of equal length and bullet-shaped proximal and mid- dle phalanges
a b
