Autosomal dominant, maternal inheritance of infantile hemangioma

1. Pedigrees of families with infantile hemangioma (IH) were consistent with 2 distinct modes of transmission: autosomal dominant transmission and maternal inheritance, both with incomplete penetrance.

2. Current discomfort from IH lesions was reported to be greater in familial cases compared to that of sporadic cases.

Study Rundown: Infantile hemangiomas (IHs), also known as “strawberry marks,” are common noncancerous tumors frequently appearing soon after birth. Following a proliferative phase, most hemangiomas shrink and resolve spontaneously over time. However, in rare cases, these vascular anomalies can be fatal (e.g., if they interfere with respiration). Although genetic risk factors for IH, such as mutations in genes involved in angiogenesis, have been reported, much remains to be learned regarding the role of genetics in this disease. To study inheritance and compare familial and sporadic cases of IH, researchers identified index cases from Helsinki University Hospital records and mapped family pedigrees. In some families, pedigree analysis was consistent with an autosomal dominant mode of transmission with incomplete penetrance, while in others the inheritance pattern was more consistent with maternal inheritance with incomplete penetrance. Although no major differences in perinatal risk factors, lesion location, and complications were noted between sporadic and familial cases, current discomfort (at an age range of 7 to 20 years) was reported to be significantly higher among familial cases. A limitation of this study was its lack of in-person examination and reliance on hospital records and questionnaires to identify the study population in addition to its retrospective nature with possible response bias. However, the results strongly support a role for genetics in the pathogenesis of IH and highlight the need for additional research to find the relevant genes. Such information could be useful for clinicians attempting to identify babies, particularly those with low birth weight, who may be at increased risk for developing IH.

Click to read the study, published today in Pediatrics

Relevant Reading: Infantile hemangiomas: an emerging health issue linked to an increased rate of low birth weight infants

In-Depth [retrospective cohort]: Electronic health records from the pediatric vascular anomaly clinic at Helsinki University Hospital were used to identify the study sample. Of the 185 children identified with true IH, 136 (74%) responded to a follow-up questionnaire assessing IH family history, perinatal information, and present IH-related discomfort (on a visual analog scale from 1 to 10). The individuals with a positive family history (i.e., those with ≥1 relative with IH) were interviewed by phone. This data was then used to construct 40 pedigrees for mode of inheritance and founder effect analysis. Two modes of inheritance, both with incomplete penetrance, were identified: autosomal dominant transmission and maternal inheritance. A founder effect was not observed. Due to the low number of twins in the study, it was not possible to perform a statistical assessment of concordance. However, of note was the identification of concordant monozygotic twins with IH lesions in the same location. As for a comparison of familial and sporadic IH cases, no significant differences were found, except that the current mean discomfort rate (as assessed by questionnaire at a mean age 10.1 years, range 7-20 years) for index cases and their IH-affected first-degree relatives was higher than that of sporadic cases (p = 0.036).

Image: PD

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