Etiology of Caudal Regression Syndrome

Abstract

Caudal regression syndrome (CRS) is a rare congenital disorder in which lumbosacral anomalies are combined with anorectal and urogenital malformations. However, the molecular mechanisms of human CRS are not yet known. Trauma, nutritional problems, toxic agents, and genetics are suggested in the etiology of CRS. To the best of our knowledge, linkage studies of families affected exclusively by CRS or total sacral agenesis have not been conducted. In spite of the small number of familial cases reported, some specific genes have been shown to cause defined phenotypes. Environmental factors also may act as an enhancer in the etiology for CRS. There are several mutant mice that are considered as models for CRS, showing characteristic vertebral, anorectal, and urogenital abnormalities. Understanding the mechanisms for CRS development gives us valuable information to understand better what mutations may cause or contribute to CRS in humans. This review highlights the current evidence that pinpoints the link to the etiology of CRS.

Sacral agenesis: a pilot whole exome sequencing and copy number study

“…Maternal type 1 diabetes confers a higher relative risk (252) for CRS than for any congenital diosorder [9]. The exact mechanism by which maternal diabetes affects fetal development in humans remains unclear [10]. While animal studies have shown that embryos exposed to higher levels of glucose develop growth anomalies, hyperglycemia has not been associated with abnormal fetal development in humans [11].…”

“…Several mutated genes including Cyp26a1 , Hoxd13 [25], Wnt-3a [26], Acd , Ptf1a , and Pcsk5 underlie a CRS-like phenotype in mice [10, 27], yet mutations in the human orthologs have never been identified in CRS patients. Interestingly, the reverse is also true; Mnx1 (formerly Hxlb9 ) mutant mice do not present Currarino syndrome features [28].…”

Sirenomelia- Report of Two Cases

“…This disturbance may result in lesions varying from minor changes in vertebrae to complete fusion of the lower limbs. 3 The embryological defect occurs at the mid-posterior axis of the mesoderm leading to arrest of progression of the mesoblastic caudal bud. Studies of axial mesoderm patterning at early gestation suggest that one or more processes of primitive streak migration, neutralisation or differentiation are compromised.…”

In utero diagnosis of caudal regression syndrome

“…The prevalence of CRS is estimated to be one in 25,000 live births (3). Genetic mutations in the coding sequences of HOXD13, CYP26A1, and HLXB9 have been suspected in the pathogenesis of CRS (4). Other factors likely to contribute include chromosomal abnormalities, vascular hypoperfusion, hyperglycemia, and exposure to minoxidil and trimethoprim-sulfamethoxazole (2).…”