[Siblings Seckel's syndrome 1 caused by ATR gene variants in a sibpair]

Area of Science:

• Genetics
• Pediatrics
• Rare Diseases

Background:

• Seckel's syndrome (SCKL1) is a rare genetic disorder characterized by prenatal and postnatal growth retardation.
• Clinical manifestations include microcephaly, intellectual disability, and distinctive facial features.

Purpose of the Study:

• To report two cases of Seckel's syndrome (SCKL1).
• To review the literature for clinical and genetic information on this rare condition.
• To highlight the utility of whole exome sequencing in diagnosing SCKL1.

Main Methods:

• Clinical data collection from two affected children.
• Whole exome sequencing (WES) for genetic analysis.
• Comprehensive literature review on Seckel's syndrome.

Main Results:

• Both patients exhibited intrauterine growth retardation, intellectual disability, microcephaly, birdhead-like face, and café au lait spots.
• Bone age was significantly delayed compared to chronological age; growth hormone levels were normal.
• Novel compound heterozygous variants (c.1A>G and c.4853-18A>G) in the ART gene were identified in both patients via WES.

Conclusions:

• Seckel's syndrome should be considered in children with prenatal onset short stature, developmental delay, microcephaly, and characteristic facial features.
• Whole exome sequencing is a valuable tool for confirming the clinical diagnosis of SCKL1.
• Identification of novel ART gene variants expands the genetic landscape of Seckel's syndrome.