Isolated sacral agenesis in a fetus monosomic for 7q36.1-->qter.

Abstract

A fetus with severe sacral agenesis and intrauterine growth retardation, ascertained at prenatal diagnosis, was found to be carrying an unbalanced form of a paternal balanced reciprocal translocation (7;19)(q36.1;q13.43), resulting in functional monosomy for 7q36.1--qter. Necropsy confirmed that the fetus had isolated sacral agenesis type II. A critical region for autosomal dominant sacral agenesis has recently been mapped to the 7q36 region. This case provides firther evidence for a sacral agenesis locus in this region and may help to refine the critical region further.

Minimal clinical expression of the holoprosencephaly spectrum and of Currarino syndrome due to different cytogenetic rearrangements deleting the sonic hedgehog gene and the HLXB9 gene at 7q36.3

“…The phenotype in 7q deletions resulting from an inherited translocation may be associated with severe HPE in a subset of cases [Morichon-Delvallez et al, 1993;Nowaczyk et al, 2000] but often only microsigns are seen [Savage et al, 1997;Frints et al, 1998 (Patient 2);Wang et al, 1999]. The trisomic parts of the involved chromosomes (our Patient 3: chromosome 10q; our Patient 4: chromosome 9p) may have contributed to the broader clinical variability in our translocation cases as compared to the pure deletion phenotypes of our Patients 1 and 2.…”

“…Symptoms of Currarino syndrome have been also noticed in four of six previous patients with de novo 7q36 deletions (Table I), and constipation and recurrent urinary tract infections were also mentioned by Frints et al [1998a (Patient 1)], but these authors described no further screening for other features of the syndrome. The association between 7q deletion and sacral anomalies is also well known from cases with unbalanced translocations [Morichon-Delvallez et al, 1993;Savage et al, 1997;Wang et al, 1999;Nowaczyk et al, 2000]. Prior to the localization of HLXB9 to 7q36, most authors hypothesized that genes for HPE and sacral agenesis might be allelic and might play a critical role in the development of both ends of the notochord .…”

Ring chromosome 7 and sacral agenesis

“…However, the infant also has partial sacral agenesis, a midline defect, which was described previously in this chromosome anomaly (Table II). Sacral agenesis also was described in patients with different chromosome anomalies, affecting chromosomes 1, 4, 7, 8, 9, 15, 17, and 18 [Schinzel, 1994] as well as in patients with terminal 7q deletions [Harris et al, 1977;Nistrup Madsen et al, 1983;Schinzel 1986;Schrander-Stumpel et al, 1988;MorichonDelvallez et al, 1993;Lozzio et al, 1995;Savage et al, 1997;Vance et al, 1998]. In fact, a region for the genes involved in the sacral agenesis was mapped recently at the end of 7q (7q36) [Lynch et al, 1995].…”

A sacral anomaly from the Quaker Cemetery, Kingston‐upon‐Thames, England

“…Like hemivertebrae, sacral agenesis is thought to arise from a disruption of genes, exposure to environmental toxins (e.g. toluene or retinoic acid) or both (Pang, 1993;Kibar et al, 2007;Szumska et al, 2008); however rare inherited forms do exist (O'Riordain et al, 1991;Savage et al, 1997;Lynch et al, 2000). In addition to environmental toxins, exogenous factors that are known to cause neural tube defects in genetically susceptible embryos include maternal nutritional deficiency in zinc, folic acid, and selenium, as well as a faulty maternal metabolism of folate (Pang, 1993).…”