An Update on Smith-Kingsmore Syndrome: Characterization of Developmental Milestones and a Review of the Literature.

Smith-Kingsmore syndrome (SKS) is a rare autosomal dominant condition characterized by neurodevelopmental differences, macrocephaly/megalencephaly, describable facial features, sleep-wake abnormalities, hyperphagia, and overgrowth. SKS is caused by pathogenic gain-of-function variants in MTOR which lead to hyperactivation of the mTOR pathway. In this review, we discuss the history, epidemiology, molecular basis, clinical features, and management considerations for Smith-Kingsmore syndrome. In addition, we provide insight on early developmental milestones through a report on 14 individuals with a confirmed diagnosis of SKS. Among these individuals, 8/12 (67%) achieved crawling at an average age of 23 months, 9/14 (64%) achieved walking with an average age of 32 months, 5/9 (56%) achieved a pincer grasp at an average age of 23 months, 8/12 (67%) achieved the ability to use a device or utensil with an average age of 3.4 years, 10/13 (77%) achieved babbling at an average age of 20 months, 8/14 (57%) achieved their first word at an average age of 34 months, and 4/14 (29%) achieved the use of short phrases at an average age of 4.6 years. This review highlights advances in characterizing the natural history of SKS since it was first described 12 years ago and the need for additional research to inform genotype-phenotype correlations and targeted therapies to support individuals with SKS.

• Publication year

  2025

• Venue

  American Journal of Medical Genetics. Part A

• Publication date

  2025-11-11

• Fields of study

  Medicine

• Identifiers
  DOI 10.1002/ajmg.a.64307PMID 41216843
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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