Seckel Syndrome 8

A number sign (#) is used with this entry because of evidence that Seckel syndrome-8 (SCKL8) is caused by homozygous mutation in the DNA2 gene (601810) on chromosome 10q21. One such family has been reported.

Description

Seckel syndrome is a rare autosomal recessive disorder characterized by intrauterine growth retardation, dwarfism, microcephaly with mental retardation, and a characteristic 'bird-headed' facial appearance (summary by Shanske et al., 1997).

For a discussion of genetic heterogeneity of Seckel syndrome, see SCKL1 (210600).

Clinical Features

Shaheen et al. (2014) studied an uncle and niece, both born of consanguineous marriages, with short stature and strikingly similar facial features consistent with Seckel syndrome. Both uncle and niece had decreased length at birth (-4.9 and -5.1 SD, respectively) and continued to have short stature at ages 18 years and 9 years (-9.5 and -6 SD) as well as severe microcephaly (-7.5 and -11.8 SD). Both had global developmental delay and intellectual disability. The uncle also had severe kyphoscoliosis resulting in spinal cord compression and paraplegia, whereas his niece had a normal spine but exhibited an ectopic kidney. Shaheen et al. (2014) noted that both parental pairs in the extended family had had numerous miscarriages.

Molecular Genetics

In an uncle and niece with short stature and strikingly similar facial features consistent with Seckel syndrome, Shaheen et al. (2014) performed autozygome analysis and found a single shared run of homozygosity on chr10:63,850,661-71,470,390 (GRCh37). Full sequencing of all genes within this interval revealed homozygosity for a 1-bp deletion in the DNA2 gene (601810.0004).