Introduction
Background
Achondroplasia is an inherited disorder of bone growth that causes the most common type of dwarfism. It is 1 of the groups of disorders collectively called chondrodystrophies.
Achondroplasia is characterized by abnormal bone growth that results in short stature with disproportionately short arms and legs, a large head with frontal bossing, a narrow thorax, a waddling gait, and characteristic facial features. Intelligence and life span are usually normal, though the risk of infant death from compression of the cervical spinal cord and/or upper airway obstruction is increased.
Achondroplasia is inherited as an autosomal dominant trait. However, approximately 80% of cases appear to be the result of spontaneous mutations. If 1 parent has achondroplasia, there is a 50% likelihood of the infant's inheriting the disorder. If both parents have the condition, the likelihood increases to 75%.
Achondroplasia can be diagnosed on the basis of characteristic clinical and radiographic findings in most affected individuals. In infants, in whom the diagnosis can be difficult, and with individuals with atypical findings, molecular genetic testing can be used to detect a mutation in the FGFR3 gene (locus 4p16.3). Such testing detects mutations in 99% of affected individuals and is available in clinical laboratories.1,2
Image shows inverted femoral physes (inverted V configuration), which contributes to a waddling gait.
Enlarged calvaria. Note the enlarged mandible.
Achondroplasia: Sagittal section of the cervical spine T2-weighted MRI showing narrowing of the foramen magnum at C1 canal, effacement of the subarachnoid spaces at the cervicomedullary junction, abnormal intrinsic cord signal intensity in this 6-year-old patient who presented with a neurologic deficit.
Pathophysiology
Achondroplasia is a genetic disorder of endochondral bone with an autosomal dominant mode of inheritance. Achondroplasia may be inherited in a homozygous or heterozygous manner. Heterozygous disease is a common skeletal dysplasia, with a rate of 1 case per 26,000 births.
Approximately 80% of all cases of achondroplasia are the result of a spontaneous mutation that causes rhizomelic shortening, a large head with frontal bossing, depressed nasal bridge, short trident hands, and lumber lordosis.
Mental and sexual development and life span are normal. Homozygous disease is lethal because of respiratory difficulties resulting from thoracic constriction.
It is important that homozygous disease be distinguished from heterozygous disease prenatally so that an informed decision can be made regarding continuation of the pregnancy. Penetrance of the gene is 100%, which means that all individuals who have a single copy of the altered FGFR3 gene have achondroplasia. The risk of achondroplasia is low when 1 parent is heterozygous; in such cases, the rate is 1 case per 50,000, or 0.002%. When both parents are heterozygous, the rate is 25%.
The skeletal changes in achondroplasia reflect retarded endochondral bone formation. The major defect occurs at the epiphyseal osteochondral junction and is associated with loss of the palisade of growing cartilaginous spicules. It is this palisade of spicules that undergoes provisional calcification and eventually ossification. Premature ossification results in a transverse barrier at the osteochondral junction. The result of this anomaly is that the long bones are abnormally short; however, because appositional growth is not affected, the bones are usually wide. The skull, which does not depend on endochondral bone formation, is large. The length of the vertebral column is relatively normal, but there is some flattening of the vertebral bodies; because of other changes in the body habitus, kyphoscoliosis and other vertebral deformities are relatively common.
The achondroplastic foramen magnum is small at birth. During the first year, its rate of growth is severely impaired, especially in the transverse dimension. This markedly diminished growth results not only from abnormal endochondral bone growth but also from abnormal placement and premature fusion of the synchondroses.
The most important complications in people with achondroplastic dwarfism are neurologic problems related to a narrowed spinal canal. Stenosis of the spinal canal is secondary to abnormalities of endochondral ossification with premature synostosis of the ossification centers of the vertebral body and the posterior arch. This results in thickening of the laminae, shortening of the pedicles, and a reduction in the height of the vertebral bodies. Additional factors, such as prolapsed intervertebral disks, osteophytes, and progressive thoracolumbar kyphosis, contribute to the narrowing of the spinal canal.3
Patients with achondroplasia undergo dynamic changes in brain morphometry, resulting in a rostral displacement of the brainstem with gradual compression of the frontal lobes. This is the result of enlargement of the supratentorial ventricular spaces, commensurate with an increase in venous sinus distention.4
The amount of blood flow in the superior sagittal sinus is correlated with brain maturation. Hydrocephalus associated with achondroplasia is closely related to reduction in blood flow in the superior sagittal sinus — a finding that supports the hypothesis that in patients with achondroplasia, hydrocephalus results from a restriction of venous outflow.
Cine phase-contrast MRI is a convenient and effective method of measuring volumetric flow rates in vivo. In healthy children, the flow velocity is 92-196 mm/s (mean, 136 mm/s), and the flow rate is 189-688 mL/min (mean, 484 mL/min). The flow rates change in a manner that is statistically related to age: flow rate rapidly increases during the first 2 years and reaches a peak by 6-8 years of age. The flow velocity shows a similar pattern but without significant statistical correlation. In all cases of achondroplasia with hydrocephalus, both flow values are lower than the reference values by 1 standard deviation. In cases of achondroplasia without hydrocephalus, as well as in obstructive hydrocephalus, the values are not reduced.5
Frequency
United States
Achondroplasia is the most common inherited disorder involving disproportionate shortness of stature. It occurs in 1 in 15,000-40,000 live births.
International
No data suggest that the incidence of achondroplasia in other countries differs from that in the United States.
Mortality/Morbidity
- An increased risk of sudden death in the fourth and fifth decades is reported. The cause of this increased mortality is not known.
- Approximately 7.5% of infants with achondroplasia die in the first year of life from obstructive apnea or central apnea.6 Infants who are homozygous for achondroplasia seldom live beyond a few months. Homozygous achondroplasia, caused by the presence of 2 mutant alleles at nucleotide 1138 of the FGFR3 gene, is a severe disorder associated with radiologic changes that are qualitatively different from those of achondroplasia. Early death results from respiratory insufficiency associated with the small thoracic cage and neurologic deficit resulting from cervicomedullary stenosis.
- Heart disease-related mortality, which occurs in patients 25 to 35 years of age, is more than 10 times higher than mortality seen in the general population. Overall survival and the average life expectancy for patients with achondroplasia is decreased by 10 years.7
- For morbidity and complications, see Complications in the Clinical Details section below.
Race
No racial predilection is known for achondroplasia.
Sex
A minor male preponderance is observed in achondroplasia.
Age
Achondroplasia can be detected antenatally. Complications from achondroplasia affect all age groups. Patients with the homozygous type of achondroplasia seldom survive infancy.
Anatomy
Skeletal anomalies associated with achondroplasia reflect retarded endocardial bone formation. Therefore, the long bones are short but wide because appositional bone growth is unaffected. The skull is not dependent on endocardial bone; therefore, it is generally large. The spinal column is of relatively normal length but becomes kyphotic as a result of vertebral anomalies and body habitus.
Presentation
Clinical features
The features of achondroplasia are usually apparent at birth. These include typical facial features, disproportionate short stature, and rhizomelic shortening (ie, shortening of the proximal ends of the limbs). Most affected individuals develop normal intelligence. Motor delays are not unusual in infants, but cognitive function develops normally. In infancy, mild to moderate hypotonia is typical, and the acquisition of developmental motor milestones is often delayed. Infants have difficulty supporting their heads because of both hypotonia and the large size of the head. Special developmental charts are available for assessing the development of children with achondroplasia; these charts show growth curves typical of children with achondroplasia. The final adult height is in the range of 4 feet.
The characteristic feature is a large head with frontal bossing. The midface is often small; the nasal bridge is flat, and the nostrils are narrow. Middle ear infections are common in infancy and childhood because of the small size of the nasal passages and because of dysfunction of the eustachian tubes. Persistent ear infections may result in hearing loss. The mandible is large relative to the rest of the face; this may give rise to dental crowding.
Respiratory problems may occur in infants and children. Airway obstruction may be either central in origin (owing to compression of the foramen magnum) or obstructive in origin (owing to narrowing of nasal passages). Symptoms of airway obstruction include snoring and sleep apnea. Affected individuals tend to sleep with the neck in a hyperextended position.
Dwarfism associated with achondroplasia is primarily the result of rhizomelic shortening of the limbs. The legs are usually straight in infancy, but valgus knees develop when the child starts walking. As the child continues to walk, the knees acquire a varus position. The fingers and toes are short. Infants have a thoracolumbar kyphosis in the sitting position. Infants with achondroplasia often have reduced muscle tone.
Some children and some affected adults develop neurologic complications. Infants may develop hydrocephalus. Infants should be monitored regularly by means of measurements of head circumference. Symptoms of cord compression may occur at the level of the foramen magnum. Symptoms of cord compression at the foramen magnum include apnea and cervical myelopathy.
The risk of lumbar spinal canal stenosis is increased; stenosis is associated with compromise of the spinal cord or the exiting nerve root. Symptoms of such compromise include weakness, paresthesias, and pain that radiates to the lower limbs. One characteristic feature of stenosis of the spinal canal is the relief of pain when the patient assumes a squatting position. As the condition worsens, pain in the low back or buttocks occurs.
The clinical features of achondroplasia can be summarized as follows:
- Short-limbed rhizomelic dwarfism with shortening of the arms and legs
- Redundant skin folds on the limbs
- Large head with prominent forehead (frontal bossing)
- Midface hypoplasia, saddle nose
- Trident configuration of the hands
- Limitation of elbow extension
- Gibbus in the thoracolumbar region in infants; swayback with prominent buttocks in children and adults; waddling gait
- Genu varum
Complications
People with achondroplasia seldom grow taller than 5 feet in height. Complications include hydrocephalus, spinal stenosis, and club feet. The most common cause of medical complaint in adulthood is symptomatic spinal stenosis involving L1-4.8 Low lumbar levels are usually not involved.
Fowler and associates described 8 cases of communicating hydrocephalus in children with genetic metabolic disorders: 1 case of mucopolysaccharidosis I (MPS I or Hurler syndrome); 1 case of MPS II (Hunter disease); 4 cases of MPS III (Sanfilippo syndrome, 2 of which affected siblings); and 2 cases of achondroplasias.9 The authors recommended surgical treatment of the latter but were doubtful about treatment of the former, in which case hydrocephalus was only a contributing cause to severe dementia.
Mantle and Kingsnorth described an unusual cause of back pain in a 47-year-old man with achondroplasia who presented with lower back pain that radiated to his left loin.10 An intravenous urogram (IVU) showed hydronephrosis on the left side and a dilated left ureter passing down into the left inguinal region. A CT scan confirmed the presence of a left inguinal hernia, which contained the left ureter and caused ureteric obstruction. The hernia was repaired and the ureter replaced retroperitoneally. A postoperative IVU indicated recovery of renal function; however, the left ureter remained persistently dilated, although it was not obstructed.
The large head of the newborn with achondroplasia increases the risk of intracranial bleeding during vaginal delivery. Hydrocephalus may be caused by an increase in intracranial venous pressure that is a result of stenosis of the sigmoid sinus at the level of the narrowed jugular foramina. Recurring otitis media is frequently a problem.
Approximately 7.5% of infants with achondroplasia die in the first year of life from obstructive apnea or central apnea.6 Obstructive apnea may result from midface hypoplasia. Brainstem compression is common and may cause abnormalities of respiratory function, including central apnea. In 1 study, 10% of infants had craniocervical junction (CCJ) compression with abnormality of the cervical spinal cord.11 All children who underwent surgical decompression of the CCJ had marked improvement of neurologic function.
Obesity is a major problem in patients with achondroplasia. Excessive weight gain is manifest in early childhood. Until a height of about 75 cm is reached, the mean weight-to-height ratios for children with average stature and for children with achondroplasia are virtually identical. Above a height of 75 cm, the weight-to-height ratio for patients with achondroplasia exceeds that of the general population.12 In adults, obesity may increase the morbidity associated with lumbar stenosis; in addition, it may contribute to nonspecific joint problems and possibly to early mortality from cardiovascular complications.6
Limited elbow extension occurs in about 70% of patients and is primarily caused by posterior bowing of the distal humerus; posterior dislocation of the radial head (about 20% of patients) results in greater loss of elbow extension.13
The incidence of neurologic deficits in patients with achondroplasia is by no means negligible. Morphologic abnormalities of the spinal canal exist from birth, and signs of cervical cord involvement are not uncommon in children. The delayed occurrence of clinical symptoms related to narrowing of the thoracolumbar canal may be explained by other acquired abnormalities, such as kyphosis, disk prolapse, and degenerative spondylosis. The clinical history usually indicates an insidious onset. The most frequent symptoms are motor weakness of the lower limbs (82.8%) and low back pain (77.1%). Sensory and/or sphincter disturbances appear to be less frequent (about 40%).
The incidence of neurologic complications in patients with achondroplasia is 20-47%. Symptoms are often subtle, though they are associated with serious conditions such as cervicomedullary compressive syndromes, syringomyelia, or hydrocephalus. Therefore, the early identification of this disorder is important.
Ruiz-Garcia et al prospectively examined 39 patients (20 female, 19 male; age range, 3 mo to 17 y; mean, 4 y 6 mo).14 All patients had hypotonia and psychomotor delay; 3 had recurrent apnea; 1 developed radicular syndrome; and 1 had leg paresthesias. For 5 patients, CT scans were normal; 20 patients had cortical atrophy; and 18 patients had communicating hydrocephalus. The authors identified foramen magnum abnormalities in 28 patients and reduced CCJ with cervicomedullary compression in 6. Myelography and myelotomography demonstrated spinal compression in 12 patients. MRI showed cervicomedullary infarct in 1, syringomyelia in 2, and diastematomyelia in 1.
In this study, somatosensory evoked responses (SSERs) were useful in the early identification of brainstem and spinal abnormalities. The authors concluded that the neurologic manifestations of pediatric patients with achondroplasia are frequent and important. Such neurologic findings require comprehensive clinical evaluation, especially in patients with severe hypotonia or alterations in SSERs, although such evaluation is required even in asymptomatic patients.
Differential diagnosis and other problems to be considered
Although more than 100 skeletal dysplasias that cause short stature are recognized, many are extremely rare, and all have clinical and radiographic features that readily distinguish them from achondroplasia. In contrast to many of the other skeletal dysplasias, the findings of achondroplasia are present at birth, but they are not associated with respiratory insufficiency. Results on antenatal sonograms either suggest or confirm most skeletal dysplasias.
Conditions that may be confused with achondroplasia include the conditions discussed below.
Achondrogenesis
Achondrogenesis (Parenti type I, Fraccara type 1A, Houston-Harris, Fraccara type 1B; 20%) is a lethal autosomal recessive dwarfism. Both endochondral ossification and membranous ossification are affected; the calvaria, spine, and long bones may be involved, with frequent rib fractures. Short-limbed dwarfism is severe. The skull and the rest of the skeleton are poorly ossified. Chest narrowing is marked, but the head is not enlarged relative to the trunk. Polyhydramnios is usually present.
Langer-Saldino syndrome (80%) is also autosomal recessive. It is less severe than type 1 endochondral ossification. This syndrome involves variable calcification of calvaria and spine, with no rib fractures; it is a lethal short-limbed dwarfism of the long-bone type. The head is large relative to the rest of the body. Prominent skin folds are present over a short neck, small chest, and distended abdomen, with fetal hydrops. The patients' short limbs are extended away from the body.
Chondroectodermal dysplasia
Chondroectodermal dysplasia, or Ellis-van Creveld syndrome, is an autosomal recessive disorder with variable expression. The ribs are severely shortened. This disease is associated with short limbs, narrow thorax, polydactyly, postaxial hexadactyly, and congenital heart disease; approximately 50% of patients have a large atrial septal defect. The size of the thorax is particularly striking when compared with the abdomen and head.
Asphyxiating thoracic dystrophy
Asphyxiating thoracic dystrophy (Jeune syndrome) is an autosomal recessive disorder. Patients present with an extremely narrow thorax, rhizomelic short-limb dwarfism, polydactyly, and renal dysplasia (renal cysts).
Osteogenesis imperfecta
Osteogenesis imperfecta type IIa is a lethal autosomal dominant condition. Patients present with a thin skull vault that may collapse and with short limbs that are thickened and angulated because of multiple fractures.
Osteogenesis imperfecta types I, III, and IV are autosomal dominant or sporadic disorders. Patients have normal body proportions and fractures with normal bone lengths.
Congenital hypophosphatasia
Congenital hypophosphatasia is an autosomal recessive disorder; the homozygous type is associated with severe deficiency of alkaline phosphatase and increased excretion of phosphoethanolamine. Severe demineralization of the bones is present. The incidence is 1 case per 100,000 births.
Four types are described: neonatal (congenital), juvenile, adult, and latent. The last is a mild form thought to be autosomal dominant. Sonography shows short-limbed dwarfism characterized by thin, delicate bones with reduced echogenicity. First-trimester chorionic sampling with alkaline phosphatase assay may establish the diagnosis.
Metatrophic dysplasia
Metatrophic dysplasia has varied inheritance; it is associated with a narrow thorax, kyphoscoliosis, relatively long trunk, and a tail-like appendage over the sacrum.
Roberts syndrome
Roberts syndrome, or pseudothalidomide syndrome, is autosomal recessive with variable expression. Patients usually present with tetraphocomelia and a midline facial cleft. Chromosomal analysis shows a classic abnormality in which the centromere region is fluffy.
Diastrophic dysplasia
Diastrophic dysplasia is an autosomal recessive disorder with multiple contractures and hitchhiker's thumb (ie, more muscle mass than arthrogryposis).
Short rib–polydactyly syndrome types I, II, and III
Type I disease, or Saldino-Noonan disease, is autosomal recessive; it is characterized by severely shortened ribs and/or narrow thorax; short limbs; polydactyly; cardiovascular and genital anomalies; polycystic kidneys; and pointed metaphysis (an important differentiating feature).
Type II disease, or Majewski disease, is associated with short limbs, narrow thorax, polydactyly, cardiovascular anomalies, polycystic kidneys, genital anomalies, disproportionately short tibia, and cleft lip and palate. The short tibia and cleft lip and palate are important differentiating features.
Type III disease, or Naumoff disease, is associated with short limbs, narrow thorax, polydactyly, and cardiovascular and genital anomalies. The metaphysis may be wide, with marginal spurs.
Nephroblastomatosis
Large polycystic kidneys, occipital encephalocele, microcephaly, or polydactyly may be associated with any type of short rib-polydactyly syndrome.
Spondyloepiphyseal dysplasia congenita (camptomelic dysplasia)
Spondyloepiphyseal dysplasia congenita (camptomelic dysplasia) is autosomal dominant. This disease has variable expression. It is associated with short and bowed femora, a short spine and trunk (delayed ossification centers, calcaneus and talus), anterior bowing of the long bones of the lower extremities, anomalies of cervical and thoracic spine with spinal scoliosis, and hypoplastic or absent scapulas.
Thanatophoric dysplasia
Thanatophoric dysplasia occurs sporadically and represents the most common lethal skeletal dysplasia. About 14% of patients have a cloverleaf skull. This disease may be transmitted in an autosomal recessive manner. It is characterized by marked narrowing of the thorax and marked micromelia; enlargement of the head (with a prominent forehead); occasional hydrocephalus; and polyhydramnios. The soft tissues of the limbs may be thickened. Thanatophoric dysplasia is more common in male fetuses than in female fetuses.
Fibrochondrogenesis
Fibrochondrogenesis is an autosomal recessive disorder associated with a thin skull vault, which may be poorly echogenic and difficult to identify. Collapsed sutures are occasionally seen. The limbs are short and thin, and the ribs are thin and poorly visualized. The spine is poorly mineralized and poorly visualized, and the metaphyses are widened.
Chondrodysplasia punctate (rhizomelic type)
Chondrodysplasia punctate (rhizomelic type) is associated with severe micromelia of the humeri and femora; multiple joint contractures; and dorsal and ventral ossification of the vertebral body, which is separated by a cartilaginous bar.
Kniest dysplasia
Kniest dysplasia is an autosomal dominant disease associated with kyphoscoliosis, short trunk, broad thorax, and widened metaphyses. The prognosis is usually good.
Mesomelic and acromesomelic dysplasia
Mesomelic and acromesomelic dysplasia are autosomal recessive or autosomal dominant conditions associated with micromelia of the middle or distal segments. The distribution of shortening differentiates these conditions from other lethal syndromes.
Hypochondroplasia
Hypochondroplasia is characterized by phenotypic and genetic heterogeneity. It is often difficult to differentiate hypochondroplasia from other conditions involving disproportionate short stature.
Prinster and associates examined 21 patients with suspected hypochondroplasia on the basis of radiologic criteria most often reported in the literature on this disease.15 The object was to determine the reliability of radiologic interpretation in the diagnosis of hypochondroplasia and to evaluate the most typical skeletal abnormalities. The data were correlated with molecular findings. Radiographs of the lumbar spine, left leg, pelvis, and left hand were obtained. The presence of the N540K mutation in the FGFR3 gene was verified by means of restriction enzyme digestion.
The selection of patients was made on the basis of a review of all radiographs by 2 pediatric radiologists; a second selection was made in blinded fashion, and the results were compared. Both radiologists confirmed the diagnosis in 10 of 21 patients; with regard to the other patients, the disease was excluded; there was uncertainty as to the findings; or there was disagreement as to the final interpretation of the data. The best agreement rate was obtained in the evaluation of cases involving the lumbar spine and the legs. Radiologic features of 9 patients (43%) with the N540K substitution were not remarkably different from the features reported in the patients without this mutation.
The authors concluded that, with regard to the diagnosis of hypochondroplasia, the crucial skeletal regions to focus on are the lumbar spine and legs; findings in the pelvis and hands seem to be less characteristic than those in these crucial regions. To reduce the risk of misdiagnosis, accurate radiologic and clinical evaluations are needed, especially in patients who do not have a defined genetic defect.
Pseudoachondroplasia
Pseudoachondroplasia (PSACH) is a spondyloepimetaphyseal dysplasia characterized by disproportionate short stature, generalized ligamentous laxity, and precocious osteoarthritis. Autosomal dominant inheritance has been demonstrated in many families.
Stoll described a boy with PSACH who appeared healthy at birth.16 However, by 3 years of age, the patient's height was below the fifth percentile. At age 6.5 years, he was 99 cm tall (-3.5 standard deviations), and he had bowing of the lower extremities and limitations of movement at the elbows and knees. Radiographs showed features of PSACH. Later, the patient developed kyphoscoliosis with anterior beaking of the vertebrae. Cerebral CT scanning showed a large frontal cyst communicating with the third ventricle. MRI confirmed the frontal cyst and showed dilatation of the third ventricle and the occipital horns of the lateral ventricles, as well as right frontoparietal hemispheric atrophy. At age 26 years, the patient had knee pain, difficulties with swallowing, and vertigo. Sonograms showed a large cortical cyst of the right kidney and smaller cysts in both kidneys.
Double heterozygosity in bone growth disorders
Because union between individuals of small stature is common, information regarding double heterozygosity for dominantly inherited bone growth disorders is of considerable importance.
Flynn and Pauli summarized 7 occurrences of 4 combinations of double heterozygosity: chondroplasia/spondyloepiphyseal dysplasia congenita, achondroplasia/PSACH, achondroplasia/osteogenesis imperfecta type I, and achondroplasia/hypochondroplasia (non-FGFR3 disease).17 They also reviewed additional reports from the literature. Each of the 8 examples of double heterozygosity for bone growth disorders that were described are distinct with regard to phenotypic features, severity, and expectations.
Prenatal testing
Prenatal diagnosis for high-risk pregnancies is possible. A high-risk pregnancy is one in which 1 or both parents have achondroplasia. DNA extracted from fetal cells obtained by means of chorionic villus sampling (CVS) at about 10-12 weeks' gestation or amniocentesis at 16-18 weeks' gestation is analyzed.18,19 The disease-causing allele or alleles in the affected parent or parents must be identified before prenatal testing can be performed.
In low-risk pregnancies, routine prenatal sonography may reveal short fetal limbs and raise the possibility of achondroplasia in a fetus not known to be at increased risk. Such ultrasonographic findings are usually not apparent until the third trimester. DNA extracted from fetal cells obtained by means of amniocentesis can be analyzed.
Genetic counseling
Achondroplasia is inherited in an autosomal dominant manner. More than 80% of individuals with achondroplasia have genetically normal parents; in these individuals, achondroplasia occurs as a result of a de novo gene mutation. In such parents, the risk of having another child with achondroplasia is low.
An individual with achondroplasia who has a partner of normal stature has a 50% risk of having a child with achondroplasia in each pregnancy. When both parents have achondroplasia, the likelihood of their offspring having normal stature is 25%, the risk of their offspring having achondroplasia is 50%, and the risk of their offspring having homozygous achondroplasia is 25%. When both parents have achondroplasia, they should be given the option of undergoing antenatal molecular genetic testing.
Preferred Examination
Prenatal diagnosis can be achieved with sonography. Antenatal, targeted ultrasonography is indicated in at-risk pregnancies. Conventional radiography remains the preferred modality for initial investigation for both children and adults.
Myelography, CT, CT myelography, and MRI are added when indicated, as with compressive cord symptoms at the craniocervical and thoracolumbar junctions. Both CT and MRI can be used to examine the size of the foramen magnum, which is an important determinant of compressive myelopathy of the upper cervical cord. MRI has the added advantage of depicting posterior cranial fossa anatomy and other abnormalities, such as syringomyelia and hydrocephalus.
MRI is the modality of choice in cases of suspected spinal stenosis; disk lesions; and compromise of the exiting nerve root in the lumbar region. Radiologic studies are indicated if the head circumference increases disproportionately or if symptoms of hydrocephalus develop.
Ultrasonography provides a noninvasive and fairly reliable method of assessing the ventricles of infants before the fontanels close. Ultrasonography may be supplemented with CT and/or MRI of the head to monitor for compression of the foramen magnum.20
Limitations of Techniques
Both false-positive and false-negative diagnoses may occur with antenatal ultrasonography of skeletal dysplasias. Heterozygous disease may not be recognized until late in the second trimester (>24-28 wk), because sonograms are normal early in the course of the disease.
Ultrasonography remains operator dependent. Conventional radiography is good for depicting skeletal pathology, but it is poor at providing information on the brain and spinal cord.
Myelography is invasive. Myelography has traditionally been the most useful examination in delineating the level of compression of the spinal cord or the cauda equina. However, in patients with achondroplasia, myelography is difficult because of stenosis of the lumber spine. When myelography is performed near the lumber root, there is a risk that the neurologic deficit will increase; this is particularly so in cases of kyphosis. Therefore, when myelography is necessary, the study is best performed by means of cisternal puncture; however, this step makes the procedure even more invasive than it otherwise would be.
CT exposes the patient to ionizing radiation and is limited in its capacity to portray the spinal cord and to depict structures of the posterior fossa. With CT, infants and young children may need sedation or general anesthesia.
MRI is expensive and creates problems for patients with claustrophobia. However, MRI can accurately depict anatomic encroachment on the CNS. MRI is frequently used to evaluate the brain and spinal cord in patients with achondroplasia. It cannot be performed in patients with cardiac pacemakers or in patients who have certain surgical clips or other foreign objects in the body. As with CT, young children may need sedation or general anesthesia to undergo MRI.
Differential Diagnoses
Other Problems to Be Considered
Achondrogenesis
Chondroectodermal dysplasia
Asphyxiating thoracic dystrophy
Osteogenesis imperfecta
Congenital hypophosphatasia
Metatrophic dysplasia
Roberts syndrome
Diastrophic dysplasia
Short rib-polydactyly syndrome types I, II, and III
Spondyloepiphyseal dysplasia congenita (camptomelic dysplasia)
Thanatophoric dysplasia
Fibrochondrogenesis
Chondrodysplasia punctate (rhizomelic type)
Kniest dysplasia
Mesomelic and acromesomelic dysplasia
Hypochondroplasia
Pseudoachondroplasia
Double heterozygosity in bone growth disorders
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Further Reading
Keywords
achondroplasia, osteochondrodysplasia, short-limb dwarfism, dwarfism, inborn genetic disease, bone growth disorder, bone disease, developmental bone disease, chondrodystrophia fetalis, hypoplastic chondrodystrophy, chondrodystrophies, achondroplastic dwarfism, Parrot's disease, rickets fetal, ACH, metatrophic dwarfism II, Kniest syndrome, Kniest's syndrome, pseudoachondroplasia, PSACH, FGFR3 gene
