Further delineation of novel 1p36 rearrangements by array-CGH analysis: Narrowing the breakpoints and clarifying the “extended” phenotype

High resolution oligonucleotide array Comparative Genome Hybridization technology (array-CGH) has greatly assisted the recognition of the 1p36 contiguous gene deletion syndrome. The 1p36 deletion syndrome is considered to be one of the most common subtelomeric microdeletion syndromes and has an incidence of ~ 1 in 5000 live births, while respectively the “pure” 1p36 microduplication has not been reported so far.We present seven new patients who were referred for genetic evaluation due to Developmental Delay (DD), Mental Retardation (MR), and distinct dysmorphic features. They all had a wide phenotypic spectrum. In all cases previous standard karyotypes were negative. Array-CGH analysis revealed five patients with interstitial 1p36 microdeletion (four de novo and one maternal) and two patients with de novo reciprocal duplication of different sizes. These were the first reported “pure” 1p36 microduplication cases so far. Three of our patients carrying the 1p36 microdeletion syndrome were also found to have additional pathogenetic aberrations. These findings (del 3q27.1; del 4q21.22–q22.1; del 16p13.3; dup 21q21.2–q21.3; del Xp22.12) might contribute to the patients' severe phenotype, acting as additional modifiers of their clinical manifestations. We review and compare the clinical and array-CGH findings of our patients to previously reported cases with the aim of clearly delineating more accurate genotype–phenotype correlations for the 1p36 syndrome that could allow for a more precise prognosis.

► Array-CGH greatly assists the recognition of 1p36 microdeletion/microduplication.
► We present five new patients with a variable and somewhat atypical 1p36 phenotype.
► We describe two cases with the first reported “pure” 1p36 microduplication so far.
► Additional pathogenic aberrations might act as modifiers of patients' phenotype.
► Analysis of new cases will permit more accurate genotype–phenotype correlation.