Imaging findings in achondroplasia reflect gross anatomic changes. The ilia are broad and squared, with constricted sciatic notches. The pelvic inlet has a “champagne glass” configuration. The sacrum is horizontal and deeply seated in the pelvis. The ribs are broad and short, resulting in a diminished anteroposterior (AP) dimension of the thorax. The sternum is short and broad. The long and tubular bones are shortened and the developing metaphyses flared. Limb shortening is more profound proximally than distally (rhizomelic micromelia). ¹⁴⁰

Epiphyseal changes may resemble a variety of epiphyseal dysplasias. Broad, short proximal phalanges, with short middle phalanges of the feet and (more classically) the hands may occur. This results in a clinically apparent, trident-shaped hand in infants. (The trident is a three-pronged spear wielded by the fish-god of classical mythology.)

As limb-lengthening procedures pioneered by the Russian physician Ilizarov have become more widely used, clinicians may encounter patients with atypical postoperative long bone changes. ^29,53 A number of studies have shown impressive gains in limb length in patients treated with this procedure. ^5,75,194

Studies in growth hormone therapy for achondroplasia are not extensive, although subjects receiving growth hormone demonstrate sustained increases in rate of growth for 4 to 6 years. ^{30,109,179,293}

Plain films highlight most of the characteristic spinal abnormalities, including short pedicles and diminished central spinal canal dimensions (Fig. 8-1), with a cephalocaudal decrease in the coronal interpediculate distance. However, advanced, cross-sectional imaging (magnetic resonance imaging [MRI] or computed tomography [CT]) is necessary to directly identify the classic trefoil central spinal canal morphology and resultant compression of neural elements (Figs. 8-2 and 8-3). Posterior vertebral body scalloping results from vertebral dysplasia and dural ectasia. Platyspondyly is typical, although it may not be remarkable.

Degenerative disc disease and facet arthrosis are common in older adult patients because of biomechanical and gross anatomic factors. Degenerative disc and joint disease often is premature and may be unusually severe for age. Vertebral spondylophyte and hypertrophic degenerative facet joint changes may contribute significantly to central canal and nerve root canal stenosis, superimposed on a developmentally small canal dimension. The surgical approach to treatment may range from single-level laminectomy to complete craniospinal decompression from brainstem to cauda equina. This reportedly (and incredibly) does not produce spinal instability. ²⁷³

Cleidocranial dysplasia is characterized by multiple wormian (intrasutural) bones, especially within the lambdoid suture, frontal bossing of the calvarium, and variable hypoplasia and dysplasia of the clavicles (Fig. 8-4). Examination of the development of the cranium in neonates with this condition has revealed a marked delay in skeletal maturity over the first 6 months of life. Also, normal mineralization of the calvarium typically is grossly reduced. Calvarial size may be relatively normal, considering marked postpartum deformity secondary to the poor mineralization. Widening of the skull has been reported in some cases. About 60% of patients have an inverted “pear-shaped” calvarium and a persistent anterior fontanelle, one of the midline defects typical of this disorder. The portion of the skull base formed through enchondral ossification is narrowed and shows delayed ossification. Also apparent is cephalad displacement of the clivus and sella turcica, with anteriorly facing foramen magnum, often accompanied by basilar invagination. The sphenooccipital synchondrosis is widened. ^117,119

Fewer than 10% of patients show complete agenesis of the clavicles. ³² Other clavicular anomalies involving hypoplasia and dysplasia are consistent and specific enough that the diagnosis may be at least suspected in utero. ⁹⁵

The paranasal sinuses are characteristically absent or hypoplastic, consistent with an abnormality predominating in bones formed, through intramembranous ossification. The sella turcica often is hypoplastic, and the dorsum sellae often is bulbous. Nasal bones almost always are hypoplastic or agenetic. Likewise the zygomatic arches are hypoplastic or absent. ¹¹⁹ All craniofacial regions are affected in cleidocranial dysplasia. ¹¹⁷ Even the hyoid bone may demonstrate decreased ossification. ²¹⁰ The height and width of the mandible and maxilla are decreased, with anterior inclination of the mandible. ¹¹⁷ The coronoid process of the mandible is slender and obliquely oriented in a posterosuperior direction. Persistence of a midline suture at the mandibular symphysis is classic for cleidocranial dysplasia. ⁶⁵ Facial abnormalities appear to progress with increasing age and may not be readily apparent in younger children. ^119,120

Other anomalies include incompletely descended, hypoplastic scapulae with shallow glenoid fossae. The iliac wings are hypoplastic and ossification of the pubic bones and obturator rings is delayed and deficient. Pubic diastasis is a characteristic feature. Coxa vara or valga may occur, with the latter more common. Long bones may be overtubulated (excessively constricted at the diametaphyseal junctions). Fibular agenesis or congenital pseudoarthrosis of the femur may occur.

The predominant finding in the spine is spina bifida occulta, most commonly in the cervicothoracic region. Another potential anomaly is structural scoliosis resulting from vertebral segmentation anomalies, including hemivertebrae and asymmetric nonsegmentation (block vertebrae). The hands may demonstrate hypoplasia of carpal bones and distal phalanges, with relative hyperplasia of the epiphyses, especially of the distal phalanges. ²¹¹ The second and fifth metacarpals typically are long, and the second and fifth middle phalanges are short. Supernumerary ossification centers may be apparent.

Radiographic changes are consistent with the dwarfing and diffuse skeletal deformities seen clinically (Fig. 8-9). Severe peripheral deformities typically lead to early, advanced degenerative joint disease, which may necessitate arthroplasty. ¹⁹³ Tubular bones are markedly shortened and metaphyses are widened, which does not help much in distinguishing this from other dwarfing conditions.

The first metacarpal is characteristically more severely affected and may be oval in shape. The carpal bones may demonstrate multiple accessory ossification centers, premature ossification, and deformity.

The appearance of epiphyseal ossification centers is delayed, and other epiphyseal changes, which tend to be most marked at the proximal femora, resemble those of severe Legg-Calvé-Perthes disease. Developmental joint space narrowing may occur, and equinovarus deformity is common. ²¹¹

Severe cervical kyphosis resulting from dysplastic vertebrae occurs in about one third of patients and may reach 180 degrees, with the spine literally folded in upon itself. Unlike extremity deformities, which typically increase as the child ages, some of these kyphoses completely resolve by adulthood. Others may lead to myelopathy or even death. ¹⁵ Scoliosis occurs in about one third of all patients, but it is more common in female patients (approximately 50%). Although they typically develop at a much younger age than idiopathic scolioses (usually apparent by 2 to 4 years of age), fewer than 15% of these curves progress beyond 50 degrees. ²⁰¹ Diastrophic dysplasia represents a rare cause of atlantoaxial subluxation. ²¹² Congenital central spinal canal stenosis often occurs, with a narrowed interpediculate distance, although this is not as marked or consistent as in achondroplasia.

The single most important articulation to evaluate in a patient with Down syndrome is the atlantoaxial articulation, with anterior atlantoaxial dislocation or instability in approximately 20% of affected individuals. ¹⁷⁰ The most critical ligamentous structure to assess is the transverse ligament. The most crucial plain film study is a lateral cervical film with head nod or flexion to evaluate for anterior atlantoaxial subluxation or the far less common occipitoatlantal instability. This is essential, especially with patients in whom activity, anticipated therapy (especially spinal manipulation), or past atlantoaxial surgical fusion may place the upper cervical complex or craniovertebral junction at increased risk. ²²¹

The relationship between Down syndrome and congenital laxity of the transverse portion of the cruciate ligament of C1 is well known, and is generally considered to be the primary etiology for most cases of atlantoaxial instability and subluxation. However, other factors such as odontoid hypoplasia and dysplasia along with upper respiratory infections and trauma are believed to contribute. ^159,270 The atlantoaxial relationship in Down syndrome does not tend to change significantly over time, at least in asymptomatic individuals. Unless a clinical indication exists, serial lateral and flexion lateral cervical radiographs typically are not warranted. ²⁰⁵

A lesser-known, associated anomaly is a developmentally short posterior arch of C1, seen in more than one fourth of patients in one study. ¹⁶⁰ This could present a sort of “double jeopardy” in the presence of atlantoaxial instability. This anomaly is readily detected on lateral cervical radiographs and appears as an anterior displacement of the spinolaminar junction line of C1 relative to that of C2. When anterior atlantoaxial subluxation is present because of abnormality of the transverse ligament, it is difficult to estimate the potential contribution of a short posterior arch to spinal canal stenosis. As mentioned, Down syndrome patients also have an increased incidence of occipitoatlantal hypermobility and instability. Anteroposterior translation of the occiput between the neutral and fully flexed neck posture averages about 0.6 mm in normal individuals. A measurement of more than 1 mm in an adult implies instability. A study of 38 children with Down syndrome demonstrated an average of 2.3 mm, with a range from 0 to 6.4 mm. However, only one of these patients had symptoms that might be attributed to occipitoatlantal instability. The clinical implications are not entirely clear, but caution is indicated and craniovertebral junction instability is possible, even in the presence of an apparently stable atlantoaxial articulation. ¹⁶²

Other abnormalities of the cervical spine identified on plain film radiographs include an unusually high incidence of degenerative joint changes in the mid to upper cervical spine, congenital synostosis, and developmental platyspondyly. A relationship is reported between Down syndrome and small separate ossicles in the upper cervical region, which are thought to represent avulsions of the distal aspect of the dens rather than associated anomalies. ⁷⁶ Partial or complete hypopneumatization of the sphenoid sinus also may be noted on the lateral cervical neutral view, although typically without clinical relevance. ^170,265 Other abnormalities associated with Down syndrome include inconsequential but classic findings, such as a prominent conoid tubercle of the clavicle. ²⁸⁰

A variety of other anomalies have been reported in individuals with Down syndrome, affecting virtually all organ systems. Plain film radiography may be used to identify infants with duodenal atresia, the most common gastrointestinal anomaly, or thoracic anomalies such as diaphragmatic hernia. Angiography may demonstrate anomaly of the radial, anterior interosseous, ulnar, subclavian, or vertebral artery. ^149,209

Milder skeletal changes include rib anomalies, especially agenesis of the twelfth ribs, microcephaly with hypopneumatized sinuses, clinodactyly, and brachydactyly. Hypoplasia of the middle phalanx of the fifth digit is seen in about 60% of patients. Characteristics may include a short, arched hard palate, a small posterior fossa, and calcification of the basilar ganglia, best demonstrated on CT. ^113,215 Accessory epiphyses and supernumerary ossification centers of the manubrium may be seen in as many as 90% of patients. ^46,215 Knee pain and dysfunction should prompt an evaluation for patellofemoral dislocation, present in about 4% to 8% of individuals with Down syndrome, but rarely disabling. ⁶⁰ Infants with Down syndrome demonstrate flared iliac wings and flat acetabular roofs. In ambulatory adult patients, this may contribute to hip instability and frequently, early, advanced osteoarthritis. ¹¹²

Leukemia is one of the most serious complications of Down syndrome. About 50% of cases represent acute megakaryoblastic leukemia (AMKL). This form typically occurs by age 4, and may be preceded by transient leukemia (TL), involving a megakaryoblastosis, which clears by 3 months of age. Between 20% to 30% of infants with TL develop AMKL. ³⁰⁶ Transient leukemoid reactions, myelofibrosis, and leukemia may all result from an increased sensitivity of cells to interferon in patients with Down syndrome. This results in aberrant antigen expression, which leads to autoimmune disease. In the bone marrow, this may manifest as premature egress of blast cells (as in TL inflammation) or incomplete repair (as in myelofibrosis and binding of autoantibodies to cell nuclei), resulting in malignant transformation and leukemia. ³⁰⁵

As mentioned, atlantoaxial subluxation and instability is a second potentially life-threatening complication commonly encountered. The only clinical finding that may have some predictive value for the presence of this condition in otherwise neurologically intact individuals is gait disturbance, but the sensitivity of this finding was only 50% in 180 children with Down syndrome, with a specificity of 81%. ²³⁴ This study failed to identify any reliable clinical indicators of atlantoaxial subluxation or instability and also concluded that x-rays, like clinical indicators, were not reliable for detecting this complication. Other studies have disputed this. Measurement of the anterior atlantodental interspace on neutral and flexion lateral cervical radiographs typically is still performed to identify at-risk individuals. ^170,221,265 This includes patients being considered for spinal manipulation, participating in contact sports, and (preoperatively) being anesthetized, especially for otolaryngeal surgery. ^97,171

The imaging findings in homocystinuria may be nonspecific and are not present at birth. Osteopenia is typical and is believed to result from deficiency of collagen cross-linking rather than a gross deficiency in collagen itself. ¹⁵² The presence of osteoporosis, often with multiple compression fractures, helps to distinguish homocystinuria from Marfan’s syndrome.

Skeletal abnormalities occur in up to 60% of patients and closely resemble those of Marfan’s syndrome. Extremities are long and thin, and patients are usually above average in height. Arachnodactyly typically is seen. Multiple growth resumption lines may be present. Scoliosis, pectus excavatum, and generalized joint laxity may appear to be identical to Marfan’s syndrome. Joint contractures may occur in the knees, elbows, and digits, whereas such contractures are usually limited to the fifth digits in Marfan’s syndrome. Ligamentous laxity may result in genu valgum, patella alta, and repeated subluxations. Infants and children may demonstrate metaphyseal flaring and irregularity of epiphyseal ossification centers.

Other reports include a variety of other less common or less classic imaging findings diffusely affecting the skeleton, in addition to vascular calcification and medullary sponge kidney. ^28,31,45,168

Skull and facial changes in homocystinuria include sinus expansion, a widened diploic space, prognathism, and dural calcification. ^168,245 The spine may show early advanced degenerative disc disease, and posterior vertebral body scalloping. This appears to be a primary developmental abnormality rather than a pressure-related change, as from dural ectasia. ^28,245

The radiographic changes of homocystinuria may be distinguished from Marfan’s syndrome primarily by osteoporosis, flared metaphyses, and joint contractures, which are absent in Marfan’s syndrome. ^28,245