Caudal regression syndrome, also known as caudal dysplasia or sacral agenesis syndrome is a congenital malformation characterized by various degrees of developmental failure involving legs, lumbar, sacral and coccygeal vertebra, and corresponding segments of spinal cord due to defect in neuralisation. This results in motor and sensory deficits.

Other congenital anomalies such as gastrointestinal, genito-urinary or congenital heart disease may be present.

Pathogenesis

The embryological origin is believed to be a failure of formation of the most distal part of the notochord that will then influence on one side the development of neural and vertebral structure of the lower spine and on the other the development of the cloacal-derived structures.

Epidemiology

 overall incidence: 1 in 7,500 live births
 maternal diabetes in about 16% of cases (relative risk for a child of a diabetic mother: about 1%)

Synopsis

 vertebral anomalies

• partial or total unilateral sacral agenesis
• sacral agenesis
• sacral hypolasia
• total agenesis of the lumbar and sacral spine (absence of vertebrae above T10 is incompatible with life)

 neural tube defects

• meningomyelocele(30-40%)
• posterior spina bifida (33%)

 anorectal anomalies

• anal atresia (imperforate anus)
  • complete covered anus

• anorectal atresia
• rectovaginal fistula

 genital malformations

• malformed external genitalia

 hydrocephalus
 dermoid cysts

 urinary malformations

• exstrophy of the urinary bladder

 renal malformations

• bilateral renal agenesis
• horseshoe kidney
• solitary kidney

 incomplete development of the pelvis
 lower limbs anomalies

• absent fibula
• short femora
• sirenomelia (fusion of the lower extremities)
  • fused femurs or common femur
  • fused tibias or common tibia without fibula
  • rudimentary unique foot

Associations

 skeletal anomalies

• hexadactily (#1267298#)
• hand agenesis (#1267298#)
• Goldenhar syndrome (#1267298#)
• Klippel-Feil syndrome (#1267298#)

 situs inversus (#1267298#, #8719727#)
 cardiovascular anomalies
 tracheoesophageal fistula

Classification (Renshaw, 1978)

 Type I: total or partial unilateral sacral agenesis.
 Type II: variable lumbar and total sacral agenesis with the ilia articulating with the sides of the lowest vertebra.
 Type III: variable lumbar and a total sacral agenesis, the caudal end-plate of the lowest vertebra resting above either fused ilia or an iliac amphiarthrosis
 Type IV : with increasing severity, soft tissues of both the lower limbs are fused. They have two femora and two tibiae with a single central fibula between the two tibiae.
 Type V : is also known as "sirenomelia" or "mermaid syndrome" wherein there is a single femur and tibia.

Etiology

 mutations in the HLXB9 gene, a member of the HLXBs gene family in type IV form of caudal regression syndrome (CRS) characterized by hemisacrum
 maternal diabetes
 maternal prediabetes

Differential diagnosis

 familial sacral dysgenesis

• familial hemisacrum
  • type 1: Cohn-Bay-Nielsen syndrome (MIM.312800) (#5783413#)
  • type 2: Currarino syndrome (Ashcraft syndrome) (MIM.176450)

See also

 anorectal malformations
 sirenomelia