Lumbosacral deficiency is a disorder consisting of absence of one or more vertebral segments and partial or complete absence of the sacrum. Sacral agenesis and lumbosacral agenesis have been variably called vertebral agenesis, sacral-coccygeal agenesis, caudal regression syndrome, caudal dysplasia, caudal dysplasia sequence, and sacral regression.^1,2 The conditions described by these terms represent a rare, complex disorder with partial or complete absence of the sacrum and partial or complete absence of the lumbar spine. At one end of the spectrum, the condition may be mild and discovered as an incidental radiographic finding (Figure 1). At the extreme end of the severity spectrum, the sacrum and lumbar spine are completely absent, and the corresponding neural elements are also absent, causing weakness or complete paralysis of motor function, usually at the level of the last radiographically visible pedicles. In some instances, several more distal segments will be preserved or there will be asymmetric motor function. There is usually comparative sparing of sensation, which is preserved more distally or may even be normal.³ Visceral deficiencies include renal anomalies, such as absent kidney, horseshoe kidney, and ectopic kidney, and anal-rectal abnormalities such as imperforate anus. Neurogenic bladder, urinary incontinence, and bowel incontinence are common and almost universally present in more severely affected patients. A substantial number of children have associated neurologic abnormalities such as myelodysplasia, tethered spinal cord, lipomeningocele, or diastematomyelia. Any of these abnormalities may affect neurologic function.⁴ Fortunately, upper limb function and intelligence are usually normal.^5,6

The management of more severely affected children presents substantial challenges to the treating orthopaedic surgeon, prosthetist, and rehabilitation team. The orthopaedic management of spinopelvic instability, hip dysplasia, hip dislocation, knee contractures, and foot deformities in more severely affected children has been controversial.

Children with partial sacral agenesis may have a normal appearance and motor function, although urinary incontinence or dribbling may occur. With total absence of the sacrum, dimpling of the buttocks may be present, and there is often substantial disproportion between the trunk and the lower limbs. When multiple lumbar spinal segments are absent, the trunk frequently has a funnel shape (Figure 2). Orthopaedic abnormalities include spinosacral instability, upper cervical instability, scoliosis, external rotation and flexion contractures of the hip, hip dislocation, and knee contractures.
Severe popliteus webbing may occur in more severely affected patients with a higher-level neurologic abnormality. With weak or absent quadriceps power, the management of knee flexion contractures is difficult, and contracture recurrence is quite common. Foot deformities, such as clubfoot and congenital vertical talus, are frequently present.^3,6,7,8

Sacral agenesis was first reported by Hohl in 1850.⁹ In 1961, Duhamel¹⁰ coined the term caudal regression to describe a spectrum of lumbosacral deficiencies. The incidence of caudal regression has been reported as 0.1 to 0.25 live births.¹ The etiology of this deficiency is likely multifactorial, but its association with diabetes has been recognized by many authors.^3,6,7,11 In a study of 22 patients with lumbosacral agenesis, Phillips et al⁶ reported that mothers of 11 of the patients had diabetes. Banta and Nichols³ reported insulin-dependent maternal diabetes in five of seven patients with sacral agenesis, Guille et al⁷ found a maternal history of diabetes in 6 of 18 patients, and Andrish et al¹¹ in 2 of 17 patients. Women with insulin-dependent diabetes have a 200 to 400 times greater risk of giving birth to an infant with caudal regression syndrome than mothers without diabetes.¹ Although much work needs to be done to establish a causative effect, insulin injections are known to cause embryonic malformations in developing chickens.¹² Nonetheless, the large number of affected patients without a history of maternal diabetes makes the exact role of diabetes unclear.

A genetic cause of lumbosacral agenesis has been postulated. The autosomal dominant HLXB9 homeobox gene located on chromosome 7q36 has been identified in Currarino triad syndrome. This condition involves sacral agenesis, imperforate anus, perianal fistulas, and a presacral mass.¹³ Postma et al¹⁴ recently discovered a mutation in the T (brachyury) gene, a member of the T-box family of transcription factors, that causes a syndrome of sacral agenesis, abnormal ossification of vertebral bodies, and a persistent notochordal canal. In four patients from three consanguineous families, homozygosity mapping was used to find a common 4.1-Mb homozygous region on chromosome 6q27 containing the T (brachyury) homolog. Sequencing of the T gene in affected individuals led to the discovery of a missense mutation, pH171R. The mutation results in diminished DNA binding and increased cell growth, and it interferes with the expression of genes involved in ossification and notochord and axial mesodermal development.

More recent studies involving whole exome sequencing and copy number studies have led to the discovery of multiple genetic features common among patients with sporadic caudal regression patients.¹⁵

The complex deformities affecting patients with lumbosacral agenesis or caudal regression are understood to be because of the interaction of multiple genetic and environmental factors such as metabolic regulation of retinoic acid metabolism affecting embryonic cell migration, differentiation, and organ development in both animal models and patients. The overlap of syndromes
with similar embryologic defects, for example, VACTERL (vertebral defects, anal atresia, cardiac defects, trachea-esophageal fistula, renal anomalies, and limb abnormalities), is recognized.¹⁶

In 1978, Renshaw⁸ recognized four consistent morphologic patterns of sacral deformity. Type I is partial or total unilateral sacral agenesis. Type II is partial sacral agenesis with a partial but bilaterally symmetrical defect and a stable articulation between the ilia. In type III, there is variable lumbar and total sacral agenesis. The ilia articulate with the sides of the lowest vertebra present. In type IV, there is variable lumbar and total sacral agenesis. The caudal end plate of the most distal vertebra rests above either fused ilia or an iliac amphiarthrosis.

More recently, Guille et al⁷ proposed a classification that attempts to predict the potential for ambulation and identifies individuals who might benefit from treatment of their lower limb deformities. Guille et al⁷ reviewed 18 patients, 13 with lumbosacral agenesis only (group I) and 5 who also had myelomeningocele (group II). The authors identified three types of spinal deformity (Figure 3). In the patients with a type A deformity, the ilia were fused in the midline or there was a slight gap between the ilia. The caudal spine articulated with the pelvis in the midline, and vertical alignment with the pelvis was maintained. One or more lumbar vertebrae were absent. Seven of eight patients in group I with a type A deformity were capable of community ambulation and, with one exception, had motor function below L3 or L4. In patients with a type B deformity, the pelvis was fused in the midline but the spinal articulation was not centered in the midline with respect to the pelvis and articulated with one of the ilia. One patient in group I with a type B deformity was a household ambulator. In patients with a type C deformity, there was agenesis of the lumbar spine and a gap was radiographically visible between the thoracic spine and the pelvis, suggesting spinopelvic instability. All of the ambulatory patients had normal or near-normal sensation. No patient with a type B or C deformity was a community ambulator. No group II patients with myelomeningocele were ambulatory.