The first case of mosaic MNX1 mutation in an adult female with features of Currarino syndrome.

Background: Currarino syndrome (CS) is a rare genetic condition characterized by the association of three major clinical signs: anorectal malformation (ARM), sacro-coccygeal bone defects, and presacral mass. Different kinds of ARM can be present such as anteriorly placed anus, imperforate anus, anorectal stenosis, rectal duplication, and fistulae. The presacral mass can be a benign teratoma, a dermoid or neurenteric cyst, anterior meningocele or hamartoma. Females are more frequently affected and usually present with associated gynecologic and urinary tract problems. CS is considered an autosomal dominant trait, with reduced penetrance and variable expressivity. CS is associated with mutations in the MNX1 gene (motor neuron and pancreas homeobox-1, previously known as HLXB9) mapped to chromosome 7q36. Heterozygous loss-of-function mutations in the coding sequence of MNX1 gene have been reported in nearly all familial CS cases and in approximately 30% of CS sporadic patients.

Case: Here, we present the case of a woman with features of CS carrying a mosaic mutation in the coding region of MNX1 gene. This is the only reported case of a CS diagnosis in which the mutation is present in less than 50% of cells.

Conclusion: The lower detection rate of MNX1 mutations in sporadic cases could similarly be explained by somatic mosaicism, mutations occurring outside the coding regions, or genetic heterogeneity.