Nicholas G. Cost, MD
Paul H. Noh, MD, FACS, FAAP
BASICS
DESCRIPTION
• The partial or complete absence of 2 or more lower vertebral bodies
• May be occult or associated with voiding dysfunction
EPIDEMIOLOGY
Incidence
• 1 in 25,000 live births
• 16% of children with sacral agenesis (SA) have a diabetic mother (1)
• 80% of cases are detected during infancy
• 20% of cases go undetected until difficulty with toilet training (at 3–4 yr of age) (1)
Prevalence
None
RISK FACTORS
• Maternal insulin-dependent diabetes
• Maternal drug exposure (Minoxidil noted in case reports) (2)
• Genetic predispositions, see “Genetics”
Genetics
• Mutations in HLXB9 gene on chromosome 7 involved in neural plate infolding (3)
• Deletion of chromosome 7q
• Currarino syndrome (4)
– Autosomal dominant
– Mutation in HLXB9 on chromosome 7
– Presacral mass, sacral agenesis, anorectal malformation
PATHOPHYSIOLOGY
• Failure of fusion or formation of lower vertebral bodies—ie, caudal regression syndrome
• Spectrum of anomalies including meningocele and anorectal malformations
• Urologic manifestations (5):
– Upper motor neuron (UMN) lesions (35%)
Detrusor hyperreflexia
Detrusor sphincter dyssynergia (DSD)
– Lower motor neuron (LMN) lesions (40%)
– No neurologic deficit (25%)
ASSOCIATED CONDITIONS
• Maternal diabetes
• Tethered cord/tethered cord syndrome
• VACTERL/VATER Association
• Currarino syndrome
– Form of caudal regression syndrome
– Hemisacrum, anorectal malformations, and a presacral mass
GENERAL PREVENTION
Avoid maternal exposures to potentially causative agents
DIAGNOSIS
HISTORY
• Urinary tract infections (UTIs) in 75% of affected children
• Gestational/birth history
• Maternal drug exposure
• Gestational diabetes
• Toilet training history
• Bowel function/constipation
PHYSICAL EXAM
• Sacral dermatome sensation is usually intact
• Lower extremity strength is usually normal
• High arched feet, claw/hammer toes are possible findings
• Flat buttocks
• Low-riding, short gluteal cleft
• Palpation of coccyx and sacrum for abnormalities
• Assess for anal location and reflex
– Bulbocavernosal reflex: Gently squeeze head of penis or clitoris and observe for anal wink
Present in most UMN lesion, absent in most LMN lesions
DIAGNOSTIC TESTS & INTERPRETATION
Lab
Assess metabolic panel
Imaging
• Lateral x-ray of lower spine
– Confirms absence of lower vertebral bodies
– Eliminates obscured image due to bowel gas on an anterior–posterior view
• Prenatal/postnatal ultrasound (US)
– Can detect defect after ossification is complete at 18-wk gestation
– Can be used to evaluate kidneys and bladder once diagnosis is confirmed
• Magnetic resonance imaging (fet al or postnatal)
– Confirms diagnosis, often shows sharp cutoff of conus medullaris at T12
Diagnostic Procedures/Surgery
• Video urodynamics/voiding cystourethrogram
– UMN lesion: Detrusor overactivity, exaggerated sacral reflexes, no voluntary sphincter control, detrusor sphincter dyssnergia (DSD), no evidence of sphincter denervation (5)
Bladder may appear thick walled with closed bladder neck (1)
– LMN lesion: Detrusor acontractility, diminished sacral reflexes, denervation of sphincter
Bladder appears smoothed walls with open bladder neck
– Vesicoureteral reflux (VUR) in 37% (1)
Pathologic Findings
N/A
DIFFERENTIAL DIAGNOSIS
• Spectrum of anomalies that include myelomeningocele and other spinal dysraphisms
• Anorectal malformations
• Sacrococcygeal teratoma
• Presacral mass
TREATMENT
GENERAL MEASURES
• Bladder management
– Consideration for clean intermittent catheterization regimen depending on status of ability to empty bladder and low pressure, state of the upper urinary tracts, and renal function status
– Potentially utilizing anticholinergics in the setting of high-pressure neurogenic bladder
• Bowel management
– Identify and treat constipation
– Anorectal manometry
• Orthopedics consultation
MEDICATION
First Line
• UMN Lesions: Anticholinergics
– Oxybutynin (Ditropan)
1 yr: No dose established
1–5 yr: 0.2 mg/kg PO BID–QID
5–12 yr: 5 mg PO BID–TID (15 mg/d max)
>12 yr: Adult dose: 5 mg PO BID–QID
XL form: 5–20 mg/d
Second Line
• UMN lesions
– Alternate anticholinergics, many not approved for children but used “off-label”
SURGERY/OTHER PROCEDURES
• UMN lesions
– Augmentation cystoplasty may be necessary depending on bladder capacity and compliance
– Done in conjunction with continent catheterizable channel (ie, Mitrofanoff)
– May require reconstructive surgery for the bladder outlet if there is concomitant incontinence from an open bladder neck.
• LMN Lesions
– Endoscopic injections of bulking agents to help with bladder neck continence
– May require reconstructive surgery for the bladder outlet if there is concomitant incontinence from an open bladder neck
– May require continent catheterizable channel (ie, Mitrofanoff) to reliably empty the bladder
• Ureteral reimplantation or endoscopic bulking agent at the ureteral orifices for persistent VUR
• Bowel management may require enemas and even include the creation of a continent catheterizable channel for antegrade enemas (MACE [Malone antegrade continence enema])
ADDITIONAL TREATMENT
Radiation Therapy
N/A
Additional Therapies
N/A
Complementary & Alternative Therapies
N/A
ONGOING CARE
PROGNOSIS
Best prognosis for successful toilet training and management of sequelae is when defect is detected early and when the child has normal lowerextremity function.
COMPLICATIONS
• Renal function deterioration
– Potential for high-pressure urinary storage transmitted to the kidneys which is deleterious for renal function
– Scarring from VUR and recurrent UTI
• Social and developmental difficulties associated with fecal/urinary incontinence
FOLLOW-UP
Patient Monitoring
• Renal/bladder US at regular intervals
– Monitor status of upper urinary tracts
• Basic metabolic panel
– Monitor renal function by a calculated glomerular filtration rate using serum creatinine
• Voiding cystourethrogram to follow status of VUR as needed
• Urodynamics every year or every other year to ensure bladder is of a safe capacity and compliance to avoid a setup detrimental to renal health
Patient Resources
• The International Sacral Agenesis Caudal Regression Association (iSACRA)
– https://sites.google.com/site/caudalregressionsyndrome/
REFERENCES
1. Wilmshurst JM, Kelly R, Borzyskowski M. Presentation and outcome of sacral agenesis: 20 years’ experience. Dev Med Child Neurol. 1999;41:806–812.
2. Rojansky N, Fasouliotis SJ, Ariel I, et al. Extreme caudal agenesis. J Reprod Med. 2002;47:241–245.
3. Ross AJ, Ruiz-Perez V, Wang Y, et al. A homeobox gene, HLXB9, is the major locus for dominantly inherited sacral agenesis. Nat Genet. 1998;20(4):358–361.
4. Lynch SA, Wang Y, Strachan T, et al. Autosomal dominant sacral agenesis: Currarino syndrome. J Med Genet. 2000;37(8):561–566.
5. Boemers TM, van Gool JD, de Jong TP, et al. Urodynamic evaluation of children with caudal regression syndrome (caudal dysplasia sequence). J Urol. 1994;151:1038–1040.
ADDITIONAL READING
N/A
See Also (Topic, Algorithm, Media)
• Caudal Regression Syndrome
• MACE (Malone Antegrade Continence Enema)
• Myelodysplasia (Spinal Dysraphism), Urologic Considerations
• Neurogenic Bladder, General
• Sacral Agenesis Image 
• Spina Bifida/Spina Bifida Occulta, Urologic Considerations
• Tethered cord/Tethered Cord Syndrome
• VACTERL/VATER Association
CODES
ICD9
• 344.61 Cauda equina syndrome with neurogenic bladder
• 596.55 Detrusor sphincter dyssynergia
• 756.13 Absence of vertebra, congenital
ICD10
• N32.81 Overactive bladder
• N32.89 Other specified disorders of bladder
• Q76.49 Other congenital malformations of spine, not associated with scoliosis
CLINICAL/SURGICAL PEARLS
• There is variability in the level of neurologic insult and resulting in bladder dysfunction. This ranges from a UMN lesion with bladderhyperreflexia to an LMN lesion with areflexia.
• Aggressive medical management with anticholinergics and CIC may prevent renal damage and the need for major reconstructive surgery.