Mutated patients showed a variability of phenotypes but all share at least the association of sacral agenesis and presacral mass, and this co-occurrence can constitute a pathognomonic sign to perform MNX1 analysis.
Previous reports identified a deletion of HLXB9 as a possible genetic cause of the caudal regression syndrome, which could not be identified in the present case.
Together with the finding that mutation of the pancreatic transcription factor HLXB9 causes sacral agenesis, our results implicate pancreatic transcription factors in the pathogenesis of birth defects associated with diabetes.
Loss of proprotein convertase subtilisin/kexin type 5 (Pcsk5) results in multiple developmental anomalies including cardiac malformations, caudal regression, pre-sacral mass, renal agenesis, anteroposterior patterning defects, and tracheo-oesophageal and anorectal malformations, and is a model for VACTERL/caudal regression/Currarino syndromes (VACTERL association - Vertebral anomalies, Anal atresia, Cardiac defects, Tracheoesophageal fistula and/or Esophageal atresia, Renal & Radial anomalies and Limb defects).
We identified nonsynonymous mutations in PCSK5 in patients with VACTERL (vertebral, anorectal, cardiac, tracheoesophageal, renal, limb malformation OMIM 192350) and caudal regression syndrome, the phenotypic features of which resemble the mouse mutation.
This case raises the question as to whether hyperglycaemia in GCK-MODY may increase the risk of fetal caudal regression syndrome as reported in women with pre-existing diabetes mellitus.
This case raises the question as to whether hyperglycaemia in GCK-MODY may increase the risk of fetal caudal regression syndrome as reported in women with pre-existing diabetes mellitus.
Mutations in the T (brachyury) gene cause a novel syndrome consisting of sacral agenesis, abnormal ossification of the vertebral bodies and a persistent notochordal canal.
We have used fluorescence in situ hybridization (FISH) and polymerase chain reaction (PCR) amplification in 5 cell lines from patients with HPE (3 cases), HPE and sacral agenesis (1 case), and microcephaly (1 case) to further define the structural rearrangements of the long arm of chromosome 7 in each case.
A multifactorial inheritance model fits with the reported patients, with the relationship to diabetes, and with the similarity of FH/UFS to caudal regression, another condition related to maternal diabetes.