First Reported Lebanese Cases of Kleefstra Syndrome Type 2, with two Novel Variants of the KMT2C Gene
MOUAWAD Mayssi1, SLAIBY Louis1, AL KARI Georges1, SNAIFER Patrick1-2, MEGARBANE Andre3-4, MANSOUR Hicham1-5*
1Faculty of Medicine, Saint George University of Beirut, Lebanon.
2Department of ENT, Head and neck surgery, Saint George University Medical Center, Lebanon.
3Department of Human Genetics, Gilbert and Rose-Marie Chagoury School of Medicine, Lebanese American University, Lebanon.
4Institut Jerome Lejeune, Paris, France.
5Department of Pediatrics, Saint George University Medical Center, Lebanon.
*Corresponding Author: MANSOUR Hicham, Department of Pediatrics, Saint George University Medical Center, Lebanon.
https://doi.org/10.58624/SVOAPD.2026.05.016
Received: May 26, 2026
Published: June 18, 2026
Citation: Mouawad M, Slaiby L, Al Kari G, Snaifer P, Megarbane A, Mansour H. First Reported Lebanese Cases of Kleefstra Syndrome Type 2, with two Novel Variants of the KMT2C Gene. SVOA Paediatrics 2026, 5:3, 115-119. doi: 10.58624/SVOAPD.2026.05.016
Abstract
Kleefstra syndrome type 2 (KLEFS2) is a rare neurodevelopmental disorder associated with pathogenic variants in the KMT2C gene. Its clinical spectrum remains incompletely defined due to the limited number of reported cases. Here we report two male patients presenting with global developmental delay and significant expressive language impairment. The first patient demonstrated early developmental regression, macrocephaly, persistent lactic acidosis, and a large hypopigmented cutaneous lesion. Brain imaging revealed minimal structural abnormalities. The second patient presented predominantly with behavioral disturbances and attention deficit hyperactivity disorder. Neuroimaging revealed delayed white matter maturation. Genetic analysis uncovered two distinct KMT2C novel variants. These cases emphasize the clinical diversity observed in KLEFS2 and highlight the importance of considering a genetic etiology in patients presenting with unexplained developmental delay. The identification of atypical features, such as metabolic abnormalities and dermatological findings, aids in refining the phenotypic spectrum of KMT2C related disorders, thereby supporting the need for thorough clinical and genetic assessment.
Keywords: Kleefstra syndrome type 2; KMT2C; neurodevelopmental disorder; developmental delay; genotype–phenotype correlation; lactic acidosis; hypopigmented lesions; Lebanese patients