A new case of Smith‐Kingsmore syndrome with somatic MTOR pathogenic variant expands the phenotypic spectrum to lateralized overgrowth. Issue 5 (8th February 2021)

• Record Type: Journal Article
• Authors: Carli, Diana; Ferrero, Giovanni Battista; Fusillo, Anna; Coppo, Paola; La Selva, Roberta; Zinali, Federica; Cardaropoli, Simona; Ranieri, Carlotta; Iacoviello, Matteo; Resta, Nicoletta; Mussa, Alessandro
• Is Part Of: Clinical genetics. Volume 99:Issue 5(2021)
• Page Start: 719
• Page End: 723
• Publication Date: 2021-02-08
• Subjects: lateralized overgrowth -- mosaic MTOR pathogenic variant -- MTOR gene -- Smith‐Kingsmore syndrome; Medical genetics -- Periodicals; 616.0420
• DOI: 10.1111/cge.13931
• Languages: English
• ISSNs: 0009-9163

Abstract

Abstract: Smith‐Kingsmore syndrome (SKS) is a rare autosomal dominant disorder caused by heterozygous germline activating pathogenic variants in mammalian target of rapamycin ( MTOR ) on chromosome 1p36. A few patients with disseminated mosaicism have been described so far and they seem to display a different phenotype when compared to germline cases. Here we report the sixth case with a disseminated mosaic MTOR pathogenic variant, a 7‐year‐old boy with hemimegalencephaly, epilepsy, developmental delay, hypomelanosis of Ito, and lateralized overgrowth. Genetic testing revealed a pathogenic variant (c.4448G > A, p.Cys1483Tyr) in MTOR with a frequency of 32% in the DNA extracted from a skin sample, 3% in saliva and 0.46% in blood. The clinical features observed in our patient further corroborate the existence of differences in phenotypic presentation of germline and mosaic SKS cases. Moreover, lateralized overgrowth, a finding never described so far in SKS, further expands the phenotypic spectrum of SKS and allows the inclusion of MTOR pathogenic variants among the several causes of asymmetric body overgrowth. Abstract :