Seckel syndrome is a rare, autosomal recessive disorder characterized by intrauterine and postnatal growth retardation resulting in dwarfism, characteristic dysmorphic features, and intellectual disability. The dysmorphic facial features characteristic of SCKL are exemplified by severe microcephaly, beak-like nasal protrusion, receding forehead and lower jaw, narrow face, micrognathia, abnormally large eyes, and malformed ears, all giving a bird-headed profile. Occasionally, clinodactyly, hip dysplasia, radial dislocation, cryptorchidism, hirsutism, clitoridomegaly, dental abnormalities, corpus callosum agenesis, and others may also be observed. More than a hundred cases of SCKL have been reported worldwide. Although the exact incidence is not known, it is assumed that 1 in every 10,000 children is born with the condition.
The first locus for SCKL to be identified, SCKL1, was localized to chromosome 3q22.1-q24. The gene was later identified to be the ATR (Ataxia-Telangiectasia and RAD3-Related) gene. The ATR protein product plays an important role in the cellular response to DNA damage and has been found to be important for both development as well as somatic cell growth. Patients affected with SCKL have been shown to have fragile chromosomes, with several break points; an effect which can be attributed to the defect in DNA repair.
In two unrelated patients with Seckel syndrome, Abou-Zahr et al. (1999) tested for hematologic abnormalities and chromosome breakage, suggesting Fanconi anemia. By Western analysis, they determined the expression of FAA and FAC, two Fanconi anemia disease gene products that together account for approximately 80% of Fanconi anemia, and found that they were expressed at similar levels to those of normal cell lines. Furthermore, the cells from the patients were resistant to the effects of mitomycin C.
Sawardekar (2005) conducted a study to establish the prevalence of major congenital malformations in children born during a 10-year period in Nizwa Hospital. Of the 21,988 total births in the hospital, one child was born with Seckel Syndrome. Sawardekar (2005) hinted at a possible genetic contribution to this congenital abnormality in this infant.
Shanske et al. (1997) reported a family of Yemeni-Arab extraction in which three sibs out of eight, the offspring of consanguineous parents, had this disorder. CNS anomalies observed included agenesis of the corpus callosum, a dysgenetic cerebral cortex, a large dorsal cerebral cyst, and pachygyria, suggesting an underlying neuronal migration disorder.