- Author: Shital Parikh, MD; Chief Editor: Jeffrey D Thomson, MD more...
Plasma can be analyzed for the FGFR3 mutation in the mother when a short-limb skeletal dysplasia is diagnosed prenatally by means of ultrasonography.[17, 8] This can be confirmatory for achondroplasia and can help the family to make educated decisions.
DNA testing can be performed when both of the parents are affected. Infants with affected genes from both the parents (double homozygous) are either stillborn or die shortly after birth.
Radiographs of the skull, spine, and extremities reveal the characteristic features. A lateral skull radiograph demonstrates midface hypoplasia, enlarged calvaria, frontal prominence, and shortening of the base of the skull. The size of the foramen magnum is diminished. (See the image below.)
A lumbar spine (anteroposterior [AP]) view reveals distinct narrowing on the interpedicular distances from proximal to distal in L1-5 (see the image below). Normally, the interpedicular distance from the cephalocaudad direction should increase. However, if this distance decreases or remains unchanged, it is abnormal. The changes should be observed in three consecutive vertebrae.
The lateral view reveals shortening of the pedicles and vertebral bodies with significant posterior scalloping. Various degrees of thoracolumbar kyphosis may be present before walking age (see the image below). This may be associated with wedging of T12 or L1. Once ambulation is established, kyphosis generally improves, and lumbar lordosis develops. The inclination of the sacrum becomes increasingly horizontal.
Scoliosis of more than 20° develops in some patients. The curves are relatively short and are located in the thoracolumbar or lumbar region. Rotation is not a prominent feature. Degenerative changes can be seen in the vertebral column, particularly at the anterior margins of the vertebral bodies located in the thoracolumbar area and in the cervical spine. However, such changes are compatible with the patient's age.
The pelvis is typically broad and short, and the ilium has a square appearance. The sacrosciatic notch is short, and the acetabular roof is horizontal (see the image below). The femoral neck is short with trochanteric overgrowth, giving an appearance of coxa vara. However, true coxa vara is not seen. Arthritic changes of the hip, even in older patients, usually are not observed. This can be attributed to the reduction of major joint lever arms and the comparative lightness (50 kg) of the patient.
The long bones have metaphyseal flaring and are short and thick. During the first year, the proximal metaphyses of the femur and the humerus have oval areas of radiolucency. Sites of major muscle attachments (eg, deltoid and patellar tendon tuberosity) are prominent. The distal femoral physes are configured in the shape of an inverted V (chevron). Bowing usually affects the tibia more than the femur. The fibula is typically longer than the tibia. The humerus is markedly shortened, and the radial head frequently is dislocated. The ulna is typically short with an elongated styloid process. The proximal and middle phalanges of the hand are broader, with greater shortening than the distal phalanges and metacarpals.
Primary radiographic criteria for diagnosis are as follows:
Decrease in interpedicular distance in the lumbar spine
Square short ilia
Short, broad neck of femur
Shortening of long tubular bones, with metaphyseal flaring
Secondary radiographic criteria for diagnosis are as follows:
Anteroposterior shortening of lumbar pedicles
Dorsal concavity of lumbar vertebra
Long distal fibula
Short distal ulna
Long ulnar styloid
The size of the foramen magnum can be measured most accurately by means of CT.[20, 21] The spinal canal is narrowed developmentally, particularly in the lower lumbar segments. The cross-sectional anatomy can be evaluated noninvasively with this modality. CT can be used to develop a three-dimensional image of the rib cage, which can be used to calculate lung volumes and can substantiate a successful surgical chest expansion.
Magnetic resonance imaging
Given the incidence and potential severity of neurologic symptoms associated with foramen magnum stenosis, a baseline MRI is strongly recommended in infancy. Cervicomedullary compression at the foramen magnum, fusion of C1, or isolated subaxial cervical stenosis can be demonstrated (see the image below). In addition, MRI can show myelomalacia, intramedullary cyst, or angulation at the craniocervical junction.
MRI may be used to establish the cause of neurocranial enlargement. Dilated ventricles without hydrocephalus, and communicating and noncommunicating forms of hydrocephalus may be observed.
MRI is also recommended for preoperative evaluation of lumbar spinal stenosis, especially to determine whether associated disc herniations exist and the proximal level of compression. The average area of L1 is decreased by 39%, and that of L5 is decreased by 27%. Kyphosis correlates strongly with neurologic symptoms, and MRI can demonstrate apical wedging and neurologic involvement.
In the fetus, heterozygous achondroplasia is associated with normal or near-normal femur lengths until 20-24 weeks of pregnancy. Thereafter, the growth rate of the femur decreases. Hence, ultrasonography may not be useful for diagnosing achondroplasia in the first half of the pregnancy. Later in the pregnancy, ultrasonography can detect short-limb dysplasia. However, differentiation among various skeletal dysplasias is difficult.
In the neonate, ultrasonography can be used to detect ventricle size and other abnormalities. It cannot be used once the sutures and fontanelles close. MRI is the imaging modality of choice at that time.
Cine-phase contrast and magnetic resonance angiography
Cine-phase contrast and magnetic resonance angiography (MRA) are useful for studying the pathophysiology of brainstem compression and hydrocephalus. Gated cine-phase contrast cerebrospinal fluid (CSF) flow studies can be used to evaluate CSF dynamics across the foramen magnum. MRA (venography) can be used to depict obstructed venous drainage due to jugular foramen stenosis. Steno-occlusive disease of the internal jugular vein, reduced blood flow in the superior sagittal sinus, and compensatory enlargement in the emissary veins can be depicted.
Somatosensory evoked potential (SSEP) abnormalities have been reported for 44% of neurologically intact persons with achondroplasia and are probably related to brainstem compression at the level of the foramen magnum.
Pulmonary function tests are useful for preoperative evaluation when respiratory symptoms are present. Typically, the vital capacity is decreased, averaging 68% for affected males and 72% for affected females.
A sleep study may be performed if symptoms suggest airway obstruction. The cause of airway obstruction can be established to guide the treatment. Differentiating between central sleep apnea (due to brain stem or upper cervical cord compression) and obstructive sleep apnea (due to midface hypoplasia) is helpful.
Reports exist of sudden blindness associated with an increase in the intracranial pressure (ICP). Hence, ICP monitoring is recommended in persons with achondroplasia with moderate ventriculomegaly, as demonstrated by MRI. This is performed with a percutaneous spinal catheter. Treatment is recommended when the ICP is higher than 15 mm Hg.
Biopsy from the growth plates of the ilium and proximal fibula reveal an essentially normal structure. Glycosaminoglycan determination is normal. The proportion of proteoglycan aggregates increases in the fibular head. The defect is mainly quantitative and lies in the proliferative zone of the growth plate.
Smoker WR, Khanna G. Imaging the craniocervical junction. Childs Nerv Syst. 2008 Oct. 24(10):1123-45. [Medline].
J. M. Parrot. Les malformations achondrodysplasiques. Bulletins de la Société d’anthropologie de Paris, 1878. 1878.
Bailey JA 2nd. Orthopaedic aspects of achondroplasia. J Bone Joint Surg Am. 1970 Oct. 52(7):1285-301. [Medline].
Nelson MA. Orthopaedic aspects of the chondrodystrophies. The dwarf and his orthopaedic problems. Ann R Coll Surg Engl. 1970 Oct. 47(4):185-210. [Medline].
Horton WA, Hall JG, Hecht JT. Achondroplasia. Lancet. 2007 Jul 14. 370(9582):162-72. [Medline].
Laederich MB, Horton WA. Achondroplasia: pathogenesis and implications for future treatment. Curr Opin Pediatr. 2010 Aug. 22(4):516-23. [Medline].
Baitner AC, Maurer SG, Gruen MB, Di Cesare PE. The genetic basis of the osteochondrodysplasias. J Pediatr Orthop. 2000 Sep-Oct. 20(5):594-605. [Medline].
Wang Q, Green RP, Zhao G, Ornitz DM. Differential regulation of endochondral bone growth and joint development by FGFR1 and FGFR3 tyrosine kinase domains. Development. 2001 Oct. 128(19):3867-76. [Medline].
Carakushansky G, Rosembaum S, Ribeiro MG, et al. Achondroplasia associated with Down syndrome. Am J Med Genet. 1998 May 1. 77(2):168-9. [Medline].
Wynn J, King TM, Gambello MJ, Waller DK, Hecht JT. Mortality in achondroplasia study: A 42-year follow-up. Am J Med Genet A. 2007 Nov 1. 143(21):2502-11. [Medline].
Hoover-Fong JE, McGready J, Schulze KJ, Barnes H, Scott CI. Weight for age charts for children with achondroplasia. Am J Med Genet A. 2007 Oct 1. 143(19):2227-35. [Medline].
Hoover-Fong JE, Schulze KJ, McGready J, Barnes H, Scott CI. Age-appropriate body mass index in children with achondroplasia: interpretation in relation to indexes of height. Am J Clin Nutr. 2008 Aug. 88(2):364-71. [Medline].
Ireland PJ, McGill J, Zankl A, et al. Functional performance in young Australian children with achondroplasia. Dev Med Child Neurol. 2011 Oct. 53(10):944-50. [Medline].
Ireland PJ, Johnson S, Donaghey S, Johnston L, Ware RS, Zankl A, et al. Medical management of children with achondroplasia: Evaluation of an Australasian cohort aged 0-5 years. J Paediatr Child Health. 2011 Nov 23. [Medline].
Lonstein JE. Treatment of kyphosis and lumbar stenosis in achondroplasia. Basic Life Sci. 1988. 48:283-92. [Medline].
Cohen ME, Rosenthal AD, Matson DD. Neurological abnormalities in achondroplastic children. J Pediatr. 1967 Sep. 71(3):367-76. [Medline].
Modaff P, Horton VK, Pauli RM. Errors in the prenatal diagnosis of children with achondroplasia. Prenat Diagn. 1996 Jun. 16(6):525-30. [Medline].
Morgan DF, Young RF. Spinal neurological complications of achondroplasia. Results of surgical treatment. J Neurosurg. 1980 Apr. 52(4):463-72. [Medline].
Erdincler P, Dashti R, Kaynar MY, et al. Hydrocephalus and chronically increased intracranial pressure in achondroplasia. Childs Nerv Syst. 1997 Jun. 13(6):345-8. [Medline].
Lugo N, Becker J, Van Bosse H, et al. Lung volume histograms after computed tomography of the chest with three-dimensional imaging as a method to substantiate successful surgical expansion of the rib cage in achondroplasia. J Pediatr Surg. 1998 May. 33(5):733-6. [Medline].
Song HR, Choonia AT, Hong SJ, Lee SH, Suh SW, Cha IH. Rotational profile of the lower extremity in achondroplasia: computed tomographic examination of 25 patients. Skeletal Radiol. 2006 Dec. 35(12):929-34. [Medline].
Jeong ST, Song HR, Keny SM, Telang SS, Suh SW, Hong SJ. MRI study of the lumbar spine in achondroplasia. A morphometric analysis for the evaluation of stenosis of the canal. J Bone Joint Surg Br. 2006 Sep. 88(9):1192-6. [Medline].
Rollins N, Booth T, Shapiro K. The use of gated cine phase contrast and MR venography in achondroplasia. Childs Nerv Syst. 2000 Sep. 16(9):569-75; discussion 575-7. [Medline].
Moritani T, Aihara T, Oguma E, Makiyama Y, Nishimoto H, Smoker WR. Magnetic resonance venography of achondroplasia: correlation of venous narrowing at the jugular foramen with hydrocephalus. Clin Imaging. 2006 May-Jun. 30(3):195-200. [Medline].
Mehta A, Hindmarsh PC. The use of somatropin (recombinant growth hormone) in children of short stature. Paediatr Drugs. 2002. 4(1):37-47. [Medline].
Bell DF, Boyer MI, Armstrong PF. The use of the Ilizarov technique in the correction of limb deformities associated with skeletal dysplasia. J Pediatr Orthop. 1992 May-Jun. 12(3):283-90. [Medline].
Brooks WC, Gross RH. Genu Varum in Children: Diagnosis and Treatment. J Am Acad Orthop Surg. 1995 Nov. 3(6):326-335. [Medline].
Gil Z, Tauman R, Sivan J, et al. [Neurosurgical aspects in achondroplasia: evaluation and treatment]. Harefuah. 2001 Nov. 140(11):1026-31, 1118. [Medline].
Kashiwagi N, Suzuki S, Seto Y, Futami T. Bilateral humeral lengthening in achondroplasia. Clin Orthop. 2001 Oct. (391):251-7. [Medline].
Mamada K, Nakamura K, Matsushita T, et al. The diameter of callus in leg lengthening: 28 tibial lengthenings in 14 patients with achondroplasia. Acta Orthop Scand. 1998 Jun. 69(3):306-10. [Medline].
Paley D. Current techniques of limb lengthening. J Pediatr Orthop. 1988 Jan-Feb. 8(1):73-92. [Medline].
Peretti G, Memeo A, Paronzini A, Marzorati S. Staged lengthening in the prevention of dwarfism in achondroplastic children: a preliminary report. J Pediatr Orthop B. 1995. 4(1):58-64. [Medline].
Pyeritz RE, Sack GH Jr, Udvarhelyi GB. Thoracolumbosacral laminectomy in achondroplasia: long-term results in 22 patients. Am J Med Genet. 1987 Oct. 28(2):433-44. [Medline].
Ravenscroft A, Rout C. Epidural anaesthesia for caesarean section in an achondroplastic dwarf. Br J Anaesth. 1999 Feb. 82(2):301-3. [Medline].
Lee SH, Modi HN, Song HR, Hazra S, Suh SW, Modi C. Deceleration in maturation of bone during adolescent age in achondroplasia-a retrospective study using RUS scoring system. Skeletal Radiol. 2008 Jul 16. [Medline].
Lee ST, Song HR, Mahajan R, Makwana V, Suh SW, Lee SH. Development of genu varum in achondroplasia: relation to fibular overgrowth. J Bone Joint Surg Br. 2007 Jan. 89(1):57-61. [Medline].
Kim SJ, Agashe MV, Song SH, Choi HJ, Lee H, Song HR. Comparison between upper and lower limb lengthening in patients with achondroplasia: a retrospective study. J Bone Joint Surg Br. 2012 Jan. 94(1):128-33. [Medline].
Schiedel F, Rödl R. Lower limb lengthening in patients with disproportionate short stature with achondroplasia: a systematic review of the last 20 years. Disabil Rehabil. 2011 Nov 23. [Medline].
Koczewski P, Shadi M. [Surgical treatment of short stature of different etiology by the Ilizarov method]. Endokrynol Diabetol Chor Przemiany Materii Wieku Rozw. 2007. 13(3):143-6. [Medline].
American Academy of Pediatrics Committee on Genetics. Health supervision for children with achondroplasia. Pediatrics. 1995 Mar. 95(3):443-51. [Medline].