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A new case of Smith‐Kingsmore syndrome with somatic MTOR pathogenic variant expands the phenotypic spectrum to lateralized overgrowth
Author(s) -
Carli Diana,
Ferrero Giovanni Battista,
Fusillo Anna,
Coppo Paola,
La Selva Roberta,
Zinali Federica,
Cardaropoli Simona,
Ranieri Carlotta,
Iacoviello Matteo,
Resta Nicoletta,
Mussa Alessandro
Publication year - 2021
Publication title -
clinical genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.543
H-Index - 102
eISSN - 1399-0004
pISSN - 0009-9163
DOI - 10.1111/cge.13931
Subject(s) - phenotype , germline , biology , genetics , germline mutation , pi3k/akt/mtor pathway , somatic cell , germline mosaicism , mutation , gene , signal transduction
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.