Seckel syndrome

Lore & Background

Seckel syndrome is an autosomal recessive disorder believed to be caused by defects of genes on chromosome 3 and 18. One form results from mutation in the ATR gene, which is central to the cell's DNA damage response and repair mechanism. A mouse model has been developed that shows a severe deficiency of ATR protein, high levels of replicative stress and DNA damage, and accelerated aging, consistent with the DNA damage theory of aging.

Reader's Guide

Seckel syndrome is significant as a model for understanding the relationship between DNA damage repair and aging. The mouse model demonstrates that ATR deficiency leads to replicative stress, DNA damage, and accelerated aging, supporting the DNA damage theory of aging. The disorder also highlights the role of the ATR gene in growth regulation and neurodevelopment. Diagnosis relies on four criteria: congenital dwarfism and postnatal growth retardation; microcephaly, large eyes, beak-like nose, narrow face, retrognathism, and malocclusion; mental handicap; and agenesis of the corpus callosum or cerebral cysts. There is no cure, only symptomatic treatment. The syndrome was named after Helmut Paul George Seckel, and the synonym Harper's syndrome after pediatrician Rita G. Harper.

Did You Know?

• Seckel syndrome is also called bird-headed dwarfism due to the narrow face and beak-like nose.
• More than half of patients have an IQ below 50.
• A mouse model of Seckel syndrome shows accelerated aging, consistent with the DNA damage theory of aging.
• One form of the syndrome is caused by mutation in the ATR gene on chromosome 3q22.1–q24.