Seckel syndrome

Seckel syndrome is a rare, genetically heterogeneous disorder, with dysmorphic facial appearance, growth retardation, microcephaly, mental retardation, variable chromosomal instability, and hematological disorders.

Seckel syndrome was described as the prototype of the primordial bird-head type of dwarfism.

Synopsis

 neonatal hepatitis (16808631)
 central nervous system anomalies

• agenesis of corpus callosum
• cerebral cyst
• primitive convolutional pattern

Pathophysiology

 increased instability at common chromosomal fragile sites in cells lacking the replication checkpoint gene ATR
 increased chromosome breakage following replication stress
 greater chromosomal instability, particularly at fragile sites, in SCKL1-affected patient cells after treatment with aphidicolin, an inhibitor of DNA polymerase alpha and other polymerases

Etiology

 Locus SCKL1 at 3q22-q24: ATR (ataxia-telangiectasia and Rad3-related protein)
 Locus SCKL2 at 18p11-q11 (MIM.606744)
 Locus SCKL3 at 14q (MIM.608664).