Background and aims Russell-Silver syndrome (RSS) is a genetically heterogeneous and phenotypically recognizable disorder characterized by IUGR followed by postnatal growth deficiency with head sparing, trigonocephaly, limb-length asymmetry, variable hypoglycemia, and learning disabilities. Hypomethylation of the paternal imprinting center 1 (IC1) of chromosome 11p15.5 and maternal UPD7 are identified in 35%–50% and 10% of affected individuals respectively.

Methods We studied the gDNA of a 16 month old Caucasian girl with growth failure and facial features consistent with RSS using Chromosomal Microarray Analysis (CMA) and DNA microsatellite genotyping.

Results Oligonucleotide-based CMA showed no copy number abnormality while SNP-array based CMA showed segmental Long Continuous Stretches of Homozygosity (LCSH) of 64 Mb in size involving chromosome 2 [2q11.1q13 (17.66 Mb), 2q22.1q31.1 (28.67 Mb) and 2q36.2q37.3 (17.69 Mb)]. DNA microsatellite analysis showed maternal isodisomy 2q of these regions. TIGD1 and MYEOV2 map to 2q37.1 and 2q37.3 and are predicted to be paternally expressed. However, causative imprinting of either gene was excluded since both genes map outside the smallest region of overlap between our patient and two unrelated patients with features of RSS reported by Bruno et al (J Med Genet, 2011) showing LCSH at 2q.

Conclusions Taken together, these results exclude possible imprinting in 2q as a cause of RSS in this child and suggest an autosomal recessive mutation which was unmasked by the segmental maternal isodisomic abnormality. Next Generation Sequence analysis of chromosome 2q regions of homozygosity identified in this child is underway and will most likely identify another novel RSS locus.