Shifting genetic patterns in anencephaly and spina bifida

Area of Science:

• Medical Genetics
• Developmental Biology
• Public Health

Background:

• Neural tube malformations, specifically anencephaly and spina bifida (ASB), exhibited a long-term decline in incidence in New York State until the mid-1950s.
• Since the mid-1950s, ASB rates have remained stable, occurring at 1 to 1.5 per 1000 births in this population.

Purpose of the Study:

• To investigate the genetic etiology of anencephaly and spina bifida (ASB) in a low-incidence population.
• To evaluate the compatibility of observed recurrence and concordance rates with genetic inheritance models for ASB.

Main Methods:

• Analysis of recurrence rates in full siblings and half-siblings.
• Assessment of twin concordance rates for ASB.
• Comparison of ASB incidence in twins versus singletons.

Main Results:

• The full sibling recurrence rate for ASB was 1.8%, which was higher than the half sibling recurrence rate of 0.8%.
• The twin concordance rate for ASB was 6.8%, exceeding the full sibling recurrence rate.
• The incidence of ASB in twins was found to be similar to that in singletons.

Conclusions:

• The observed familial aggregation patterns, including higher sibling and twin recurrence/concordance rates, support a polygenic inheritance model for ASB.
• Further research involving biochemical screening of affected families may help identify the specific genetic and molecular pathways underlying ASB.