Sacral agenesis is a rare anomaly consisting of partial (two-thirds of cases) or total (one-third of cases) absence of the sacrum, often associated with absence of other segments of the lumbar spine. The defect is usually sporadic, and it is most commonly associated with maternal diabetes (Stewart and Stoll 1979) (Fig. 3.51). Indeed, sacral agenesis is considered the most specific anomaly among the several sometimes seen in infants of diabetic mothers (Dunn et al. 1981). The association of partial or total sacral agenesis, disruption of the distal spinal cord, and lack of growth of lower extremities is referred to as caudal regression syndrome (OMIM 182940). Neurological impairment resulting from the disrupted spinal cord manifests as bladder incontinence, decreased movement and underdevelopment of the legs, contracture deformities of the lower limbs, hip dislocations, talipes equinovarus, and spinal instability. Such abnormalities as renal agenesis, imperforate anus, cleft lip and palate, and meningomyelocele are often associated. Sirenomelia, or mermaid syndrome, once considered the most severe form of the caudal regression syndrome, is now regarded as a separate entity caused by an early-onset disruptive vascular defect. The blood is diverted from the caudal structures of the fetus to the placenta via a single abnormal vessel arising from the aorta just below the diaphragm. Distal to the origin of this large vessel, the aorta gives off no tributaries before its bifurcation into the iliac arteries. The resulting malformation pattern includes a single malformed lower limb, absent sacrum, and agenesis of the rectum and genitourinary tract (Guidera et al. 1991) (Fig. 3.52 a,b). As with other disruptive vascular defects, there is significant variability of the malformative spectrum in sirenomelia.
In addition to the sporadic form, a familial form of sacral agenesis is also recognized, which can occur in isolation or in association with a presacral mass (anterior meningocele and/or presacral teratoma) and anorectal abnormalities. This association is recognized as the Currarino triad (OMIM 176450) (Lynch et al. 2000). Symptoms related to the presence of sacral anterior meningocele range from chronic constipation to rectal fistula, perirectal abscess, and meningitis. Typically, the defect in the inherited form of sacral dysgenesis consists in a 'hemisacrum,' with an intact first sacral vertebra and agenesis involving S2-5 only. Familial hemisacrum has been further categorized into types I and II, depending on whether
it is associated with anterior sacral meningocele or presacral teratoma, respectively (Welch and Aterman 1984). An additional type of familial sacral dysgene-sis, termed partial sacral agenesis, consists in a variable degree of sacral agenesis without the characteristic hemisacrum observed in types I and II, frequently taking the form of an anterior or antero-lateral sacral defect (scimitar sacrum) (Fig. 3.53) (Welch and Aterman 1984). Many of these defects are due to a dominant mutation of the homeobox gene HLXB9 (Ross et al. 1998). Cytogenetic analysis has shown 7q deletions in several cases of familial sacral agenesis and provided evidence for their location in 7q36, a region containing a gene for holoprosen-cephaly, an early malformation of the extreme rostral end of the neural tube (Lynch et al. 1995). An association of holoprosencephaly, sacral anomalies, abdominal situs ambiguous, multiple atretic bowel segments, and dilatation of the ureters have been described in an infant with a 46,XY,der(7)t(2;7) (p23.2;q36.1) karyotype as a result of an adjacent segregation of a paternal translocation t(2;7) (Nowaczyk et al. 2000). Moreover, loss of the 7q36 region during ring formation has been demonstrated in a 19-month-old girl with a ring chromosome 7 and a combination of microcephaly, growth, and developmental delay, multiple angiomas, and partial sacral agenesis (Rodriguez et al. 2000). Sacral agenesis, with or without spina bifida occulta or aperta, is a separate entity from spina bifida/anencephaly, sacral agenesis having greater evidence of autosomal dominant inheritance (McKusick; Fellous et al. 1982).
Clinical features of sacral agenesis include short intergluteal cleft, flattened buttocks, narrow hips, dis-
Fig. 3.52 a,b. Sirenomelia. Note hypoplastic lumbar vertebrae, sacral agenesis, a single pelvic bone, a single femur, partially fused tibiae, and rudimentary digits and meta-tarsals. (From Chen et al. 1998)
tal leg atrophy, and talipes deformities (planovalgus, calcaneovalgus, vertical tali). Changes in the lower extremities, resembling those of distal arthrogryposis, include flexion, abduction, and external rotation contracture about the hips, usually associated with severe flexion contracture about the knees. The severity of these abnormalities is directly related to the degree of lumbosacral spinal involvement. Neu-rologically, lumbosacral sensation is better preserved than the motor functions, and the level of the vertebral aplasia is related to the motor but not to the sensory level (Renshaw 1978; Pang 1993). In addition to orthopedic and neurological anomalies in the lower limbs, children with sacral agenesis have neuropathic vesicourethral dysfunction in virtually all cases, and vesicoureteric reflux in some cases, with an elevated risk of developing urinary tract infections and renal scarring (Wilmshurst et al. 1999). Additional findings frequently associated with sacral agenesis include spinal anomalies above the level of the sacrum (scoliosis, lower thoracic/upper lumbar apla-sia, hemivertebrae, vertebral fusions, odontoid hy-poplasia/aplasia, atlanto-axial and spinopelvic instability) (Blumel et al. 1958), hip dislocation, dural sac stenosis, tethered spinal cord (Brooks et al. 1981), syringomyelia (O'Neill et al. 1994), and bladder and cloacal exstrophy (Loder and Dayioglu 1990) (Fig. 3.54). Sacral agenesis occurs as part of the VATER association (OMIM 192350) (Toguri et al. 1981). In addition, sacral agenesis has been found in association with phocomelia of lower limbs and large skull defect (Chitayat et al. 1993), Goldenhar syndrome (OMIM 164210) (Wasilewski and Krol 1992), and Klippel-Feil syndrome (OMIM 148900) (Raas-Rothschild et al. 1988).
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