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  • Updated 07.14.2020
  • Released 03.15.1995
  • Expires For CME 07.14.2023

Sacral agenesis

Introduction

This article includes discussion of sacral agenesis, caudal dysplasia, caudal regression syndrome, Currarino syndrome, lumbosacral agenesis, sacrococcygeal agenesis, sacrum agenesis, syndrome of caudal regression, caudal regression, and hypoplasia of sacrum. The foregoing terms may include synonyms, similar disorders, variations in usage, and abbreviations.

Overview

The author reviews the clinical and pathological features of sacral agenesis, with emphasis on the resulting neurologic deficits and the association in many cases with maternal diabetes mellitus. The demonstrated wide spectrum genetic defects are reviewed in the context of molecular genetic regulation of ontogenesis of bony and neural spinal structures. Differential diagnosis from meningomyelocele, diastematomyelia, and congenital sacrococcygeal teratoma, an association with more extensive congenital anomalies, and management of the neurologic complications are discussed. The most serious complications are lack of bowel and bladder control due to anorectal atresia and flaccid neurogenic urinary bladder. The autosomal dominant Currarino triad of sacral dysgenesis, anorectal malformations, and anterior meningocele is discussed, as well as caudal regression syndrome or syringomyelia.

Key points

• Agenesis of the sacrum and sometimes lumbar and even thoracic vertebrae is a congenital malformation that occurs sporadically, associated with other complex genetic syndromes and most frequently in infants of diabetic mothers (1% of all such infants). Rarely, it may be asymmetrical as hemi-sacral agenesis.

• Because of lack of neural tube (ie, floor plate) induction by the deficient notochord, at the level of the bony dysgenesis there is a severe dysplasia of the spinal cord, often with fusion of the ventral horns, an incomplete central canal, and abnormal architecture of white matter tracts.

• Clinical neurologic expression at birth is hypoplasia or aplasia of muscles innervated by the defective ventral roots, autonomic defects, and neurogenic bladder, but relative preservation of somatic sensory function of the dorsal roots.

• In its most extreme forms there may be a “caudal regression syndrome” of sirenomelia (fusion of the lower limbs), imperforate anus and other lower intestinal and urinary collecting system anomalies or the “Currarino triad” of anorectal malformation or ectopic anus, coccygeal and partial sacral aplasia, hypoplasia or dysplasia but preservation of the first sacral vertebra, and a presacral mass that often is an anterior meningocele, dermoid cyst, midline sacral lipoma, or a neuroendocrine tumor.

• The mechanism is abnormal segmentation of the embryonic sclerotomes with secondary failure of induction of the caudal neural tube and surrounding mesodermal structures.

• A strong association with maternal diabetes mellitus is of unknown pathogenesis, but suppressed genetic expression by insulin is suspected.

• Various genetic mutations are demonstrated in sacral agenesis not associated with maternal diabetes mellitus, in both familial and sporadic cases.

Historical note and terminology

Partial or complete absence of the sacral and coccygeal bones was first described in 1852 by Hohl (67); in 1857, Wertheim published a case of complete sacrococcygeal agenesis. Over the next hundred years, about 50 additional cases were published singly or in small series. In 1959, Blumel and colleagues reported 50 more cases, many of which included other malformations such as meningoceles, anal and bowel anomalies, and abnormalities of the lower limbs often associated with dysfunction of the bowel and urinary bladder. Sacral meningocele, often anterior, was noted by Coller and Jackson in 1943 to often be associated with sacral agenesis or sacral hypoplasia (36), and this association was subsequently confirmed by other authors. Case reports confirming the early descriptions continue to appear (133; 176; 155; 16; 51; 71; 147). An association of sacral agenesis with congenital tumors in the sacral region also is described, but this situation remains rare.

The frequent occurrence of sacral agenesis in infants of diabetic mothers was pointed out by Kucera in a survey that reviewed 48 papers published between 1930 and 1964 on the topic of congenital anomalies associated with maternal diabetes mellitus during gestation (88). The total incidence of all anomalies was 4.8%, and the incidence of sacral agenesis in infants of diabetic mothers is now estimated at about 1%, a more significant association than with any other predisposing condition, including genetic factors. Other case reports continue to be published, further confirming this association (125). Preexisting maternal diabetes mellitus, type 1 more than type 2, was redocumented as a strong risk factor for nonsyndromic fetal sacral agenesis in a large, more recent National Birth Defects Prevention Study (117).

Caudal regression syndrome. The term "syndrome of caudal regression" was first used by Duhamel to describe a spectrum ranging from simple sacral agenesis to severe lower limb anomalies, including fusion as "sirenomelia," often with imperforate anus and major malformations of the anus and rectum, omphalocele, and anomalies of the genitourinary system, but sacrococcygeal agenesis or hypoplasia was the constant feature (43; 22). Rarely, there is duplication of the rectum rather than atresia or ectopia (86; 124). Children born with the syndrome or caudal regression also may lack pelvic bones and have agenesis of the fibulae and of the external genitalia, and they often live only a few hours (04). Rare cases exhibit a vestigial tail despite sacral agenesis (61), suggesting lack of induction at the sacral level and overinduction at the coccygeal level, in terms of pathogenesis. Many inconstant anomalies of multiple organ systems include single umbilical artery in one third of cases and congenital heart disease in more than half of cases as well as renal agenesis, genital anomalies, popliteal webbing, and cleft lip and palate (06; 24). Asymmetrical sacral agenesis associated with hemivertebrae occurs rarely (54). The spinal cord may terminate at midthoracic levels, with a few bony vertebrae still developed caudal to that site (15). Deficient sensory and motor innervation of muscle corresponding to the level of the dysplastic spinal cord may sometimes be improved in caudal regression syndrome by extended use of growth hormone combined with physiotherapy rehabilitation (40).

The clinical neurologic and neuropathologic findings in sacral agenesis were described by Sarnat and colleagues following fragmentary descriptions in the earlier literature and confirmed by subsequent observations (147; 116; 46; 45). Plain radiographic features had been described by many authors, and the MRI findings were systematically described by Nievelstein and colleagues (119). Radiographic and imaging findings of the bony spinal anomalies can be diagnosed at birth and prenatally as early as 26 weeks’ gestation (22; 54; Harris et al 2009; 116). Though not generally familial, caudal regression syndrome has been found in 1 of dizygotic twins (87). Hemi-sacral agenesis occurs at times (106); in 1 case, it was discovered as an incidental finding in a (99m) Tc-MDP bone scan performed for other reasons in a 69-year-old woman (79). In addition to imaging for the vertebral defects, presacral masses may be demonstrated in Currarino syndrome that are not necessarily evident on physical examination of the patient (129).

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