Caudal regression syndrome, or sacral agenesis (or hypoplasia of the sacrum), is a rare birth defect. It is a congenital disorder in which the fetal development of the lower spine—the caudal partition of the spine—is abnormal. It occurs at a rate of approximately one per 60,000 live births. Some babies are born with very small differences compared to typical development, and others have significant changes. Most grow up to be otherwise typical adults who have difficulty with walking and incontinence. Signs and symptoms This condition exists in a variety of forms, ranging from partial absence of the tail bone regions of the spine to absence of the lower vertebrae, pelvis and parts of the thoracic and/or lumbar areas of the spine. In some cases, where only a small part of the spine is absent, there may be no outward sign of the condition. In cases where more substantial areas of the spine are absent, there may be fused, webbed or smaller lower extremities and paralysis. Bowel and bladder control is usually affected. Cause The condition arises from some factor or set of factors present during approximately the 3rd week to 7th week of fetal development. Formation of the sacrum/lower back and corresponding nervous system is usually nearing completion by the 4th week of development. Due to abnormal gastrulation, the mesoderm migration is disturbed. This disturbance results in symptoms varying from minor lesions of the lower vertebrae to more severe symptoms such as complete fusion of the lower limbs. While the exact cause is unknown, it has been speculated that the condition has a combination of environmental and genetic causes, and that various types of the condition may have differing causes. Sacral agenesis syndrome (a type of caudal regression syndrome involving agenesis of the lumbar spine, sacrum, and coccyx, and hypoplasia of the lower extremities) is a well-established congenital anomaly associated with maternal diabetes mellitus. Other causes are presumably involved, as demonstrated by the rare overall incidence of caudal regression syndrome (1:60,000) compared to diabetes; however, the condition does have a greatly increased incidence among infants born to mothers with diabetes, estimated at 1 in 350 newborns of mothers with diabetes. The dominant inherited sacral agenesis (also referred to as Currarino syndrome) is very often correlated with a mutation in the Hb9 (also called HlxB9) gene (shown by Sally Ann Lynch, 1995, Nature Genetics). It was previously thought to be related