Smith Magenis (RAI1)/Miller Dieker Combination LPU019 - Detail

Smith-Magenis syndrome (SMS) is a multiple congenital anomaly syndrome characterised by mental retardation, neuro-behavorial abnormalities, sleep disturbances, short stature, minor craniofacial and skeletal anomalies, congenital heart defects and renal anomalies^{1, 2}. It is one of the most frequently observed human microdeletion syndromes and associated with an interstitial deletion of the chromosome band 17p11.2^{1, 2}.

Molecular studies in SMS patients suggest a common deletion region spanning approximately 700 kb³. The proximal boundary is within a region of overlap between the FLI1 and LLGL1 genes and the distal boundary within the PEMT gene ³. Further investigation has shown that in more than 90% of patients the deletion is brought about by recombination between flanking repeat gene clusters surrounding this SMS critical region⁴. The FLII gene⁵ maps within the critical region and has been shown to be deleted in SMS patients⁶. Deletions or mutations in RAI1 (retinoic acid induced 1) gene, which lies within the 17p11.2 locus were associated with the syndrome ^{3, 7, 8, 9}. RAI1 was shown to be the primary gene responsible for most features of SMS ^{10, 11}.

Miller-Dieker syndrome (MDS) is a multiple malformation characterised by classical lissencephaly, a characteristic facial appearance and sometimes other birth defects¹² . It is associated with visible or submicroscopic rearrangements within chromosome band 17p13.3 in almost all cases¹³. Isolated lissencephaly sequence (ILS) consists of classical lissencephaly with no other major anomalies¹⁴. Submicroscopic deletions of chromosome 17p13.3 have been detected in almost 40% of these patients¹³.

MDS is considered a contiguous gene deletion syndrome where deletion of physically contiguous genes leads to the complex phenotypic abnormalities seen in MDS. LIS1 is located at 17p13.3 and recognised as the causative gene responsible for the lissencephaly phenotype in both MDS and ILS^{15, 16}. A deletion of MDS patients always involves LIS1 together with telomeric loci to in excess of 250 kb¹⁵.

Reference:/Bibliographie/Literatur/Bibliografia

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