Increased heritability of certain types of anorectal malformations

Abstract

Purpose Various lines of evidence point to genetic causes for the diverse spectrum of anorectal malformations (ARMs); we therefore studied patterns of heritability in a large case series. Methods We searched our ARM database for all patients having family members with congenital anomalies. This group was analyzed to determine the type of ARM and the specific anomalies in affected family members. Results Thirty-nine of 1606 patients (2.4%) had a family member with a congenital anomaly. The associated non-ARM anomalies included sacral masses and gynecologic, hematologic, esophageal, duodenal, renal, and spinal anomalies. Of these, 24 patients (1.4%) had 1 or more family members with an ARM. Among females with a positive family history, 73% of patients had either a vestibular or perineal fistula, compared with only 36% in patients without a family history ( P = .0004). Among males, 35% had perineal fistulas compared with only 10% of those without affected family members ( P = .0051). Conclusions A positive family history in 1.4% is supportive of a strong genetic component to ARM. The risk of having an affected family member is significantly increased in the presence of a vestibular or perineal fistula. These new data allow for more informed counseling of families with an ARM and support the need for further genetic studies.