Currarino syndrome 7q36 deletion

The paper expands upon the variable expressivity of Currarino syndrome (CS), a rare genetic disorder characterized by a triad of anorectal malformations, sacral bony defects, and presence of a presacral mass, that is caused by variants of or chromosomal arrangements involving MNX1, mapped to 7q36.

Currarino syndrome (CS) is a rare genetic disorder characterized by a triad of anorectal malformations, sacral bony defects, and presence of a presacral mass. However, the syndrome is also highly variable with low penetrance where many affected individuals have an ‘incomplete’ phenotype. CS is considered to be autosomal dominant and variants in the gene MNX1, mapped to 7q36, are the main causes of the syndrome. Large telomeric deletions in 7q36.3 have also been associated with CS. El Amrani et al. introduce the first reported case of a terminal 7q36 deletion due to a t(7;21) translocation in two Moroccan siblings who presented with sacral agenesis combined with microcephaly, facial dysmorphic features, overgrowth, and intellectual disability (ID). Both siblings had thick arched eyebrows, and a nose resembling a beak with a prominent columella. However, the older sibling, who is 16 years old, additionally presents with a long face and more severe ID compared to his 14-year-old brother, who only faces challenges in his academic performance. Banding cytogenetics revealed an unbalanced translocation t(7;21)(q36.2;p11.3) which was inherited from their mother who had a balanced translocation. Reviewing the literature about deletions 7q36 the authors found 5 other cases where the patients had CS. Like the current case, other patients with deletions involving the same region have shown elements of the CS triad and microcephaly; however, the other cases have also reported growth delay, facial dysmorphisms, and other anomalies. It is suspected that the loss or gain of other genes in the genomic region is highly contributory to these other phenotypes. What is most notable about this case is the fact that two siblings with the same genotype for CS, have different dysmorphic characteristics. The authors use this case to emphasize the variable expressivity of CS and to highlight the importance of cytogenetics in diagnosis of rare genetic syndrome.

El Amrani et al. “Currarino Syndrome in Two Moroccan Siblings with Inherited 7q36 Deletion due to Maternal t(7;21)(q36;p11)mat: A Case Report”. “Mol Syndromol” 2024, v. 15(2):125-129.

Chromosome Disorder Outreach Inc. medical geneticist and medical advisor Dr. Iosif Lurie M.D. Ph.D examines newly published research studies to locate the most important and relevant for our members. Synopses of these articles are then posted to our website’s research pages. For more information on any article please contact info@chromodisorder.org