J Genet Med.  2019 Jun;16(1):27-30. 10.5734/JGM.2019.16.1.27.

Smith-Kingsmore syndrome: The first report of a Korean patient with the MTOR germline mutation c.5395G>A p.(Glu1799Lys)

• Lee D
• Jang JH
• Lee CG

• KMID: 2451624
• DOI: http://doi.org/10.5734/JGM.2019.16.1.27

Abstract

Smith-Kingsmore syndrome (SKS; OMIM 616638), also known as macrocephaly-intellectual disability-neurodevelopmental disorder-small thorax syndrome (MINDS; ORPHA 457485), is a rare autosomal dominant disorder, the prevalence of which is not known. It is caused by a heterozygous germline mutation in MTOR (OMIM 601231). Ten different MTOR germline mutations in 27 individuals have been reported in the medical literature to date. These were all gain-of-function missense variants, and about half of the 27 individuals had c.5395G>A p.(Glu1799Lys) in MTOR. Here, I report for the first time a Korean patient with the heterozygous germline mutation c.5395G>A p.(Glu1799Lys) in MTOR. It was found to be a de novo mutation, which was identified by whole-exome sequencing and confirmed by Sanger sequencing. The patient showed typical clinical features of SKS, including macrocephaly/megalencephaly; moderate intellectual disability; seizures; behavioral problems; and facial dysmorphic features of curly hair, frontal bossing, midface hypoplasia, and hypertelorism.

Keyword

MTOR; Germ-line mutation; Smith-Kingsmore syndrome; Megalencephaly; Intellectual disability

MeSH Terms

Databases, Genetic
Germ-Line Mutation*
Hair
Humans
Hypertelorism
Intellectual Disability
Megalencephaly
Prevalence
Problem Behavior
Seizures
Thorax