2023 ACMG Annual Clinical Genetics Meeting Digital Edition: Poster Gallery-Mosaic Potocki-Lupski Syndrome Due to a Supernumerary Ring Chromsome Containing <em>RAI1</em>

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Potocki-Lupski syndrome (PTLS) is a rare microduplication syndrome located at 17p11.2. It is characterized by speech difficulties, intellectual disability, hypotonia, sleep disorders, and failure to thrive. Common physical features include a triangular face, high cheekbones, broad forehead, prominent ears, and down-slanting eyes. PTLS is usually caused by a duplication of the RAI1 gene, which is believed to be responsible for many of the syndrome's features, including sleep disturbances. The exact mechanism by which the duplication leads to the symptoms of PTLS is still unknown.<br /><br />A case study of a patient with PTLS was presented. The patient initially presented with poor feeding, malnutrition, eczema, and speech delay. Physical examination revealed characteristic facial features and dry skin. Genetic testing revealed a mosaic supernumerary ring chromosome containing duplications at 17p12q11.2 (including the RAI1 gene) and 14q11.1q12. The duplication at 17p12q11.2 was completely overlapping with the chromosomal locus associated with PTLS.<br /><br />The chromosomal region of 17p11-p12 is prone to rearrangements due to low-copy repeats (LCRs). Supernumerary marker chromosomes (SMCs), like the one found in this patient, are rare and usually involve acrocentric chromosomes. SMC(17)s utilizing the same recombination substrates as the common 17p11.2 del/dup syndromes have been reported, but their mechanism is not well understood.<br /><br />The patient's clinical features were consistent with those seen in other cases of SMC(17), including developmental delay, poor feeding, hypotonia, and a triangular face. The size and chromosomal content of the SMC(17) and the extent of mosaicism in affected tissues can lead to phenotypic variations.<br /><br />In conclusion, this case study highlights a patient with mosaic PTLS due to a supernumerary ring chromosome containing duplications at 17p12q11.2. Understanding the genetic basis of PTLS can aid in diagnosis, prognosis, and management of affected individuals. Further research is needed to elucidate the exact mechanisms underlying the symptoms of PTLS.

Asset Subtitle

Presenting Author - Noel N. Tolvanen, BS; Co-Author - John A. Bernat, MD, PhD;

Meta Tag

Chromosomal Abnormalities

Chromosome Structure/Function

Clinical Applications of Molecular Cytogenetics

Cytogenetics

Genotype-Phenotype Correlations

Molecular Cytogenetics

Co-Author John A. Bernat, MD, PhD

Presenting Author Noel N. Tolvanen, BS

Keywords

Potocki-Lupski syndrome

PTLS

microduplication syndrome

17p11.2

speech difficulties

intellectual disability

hypotonia

sleep disorders

RAI1 gene

triangular face