TY - JOUR
T1 - Neuropsychological profile associated with KAT6A syndrome
T2 - Emergent genotype-phenotype trends
AU - Ng, Rowena
AU - Kalinousky, Allison J.
AU - Harris, Jacqueline
N1 - Publisher Copyright:
© The Author(s) 2024.
PY - 2024/12
Y1 - 2024/12
N2 - Background: KAT6A (Arboleda-Tham) syndrome is a Mendelian disorder of the epigenetic machinery caused by pathogenic variants in the lysine acetyltransferase 6 A (KAT6A) gene. Intellectual disability and speech/language impairment (e.g., minimally verbal) are common features of the disorder, with late-truncating variants associated with a more severe form of intellectual disability. However, much of the cognitive phenotype remains elusive given the dearth of research. Participants and methods: This study examined non-verbal and social skills of 15 individuals with molecularly-confirmed diagnoses of KAT6A syndrome (Mean age = 10.32 years, SD = 4.12). Participants completed select subtests from the DAS-II, the NEPSY-II, and the Beery Buktenica Developmental Test of Visual Motor Integration 6th Edition, and their caregivers completed an assortment of behavior rating inventories. Results: Findings suggest global cognitive impairment with nonverbal cognition scores similar to those for receptive language. Autism-related features, particularly restricted interests and repetitive behaviors, and broad adaptive deficits were common in our sample juxtaposed with a relatively strong social drive and low frequency of internalizing and externalizing behavioral problems. A general trend of lower performance scores on nonverbal and receptive language measures was observed among those with protein-truncating variants vs. missense variants; however, no effect was observed on caregiver rating inventories of daily behaviors. Late and early truncating variants yielded comparable neuropsychological profiles. Conclusions: Overall, study results show the cognitive phenotype of KAT6A syndrome includes equally impaired nonverbal cognition and receptive language functioning, paired with relatively intact social drive and strengths in behavior regulation. Emergent genotype-phenotype correlations suggest cognition may be more affected in protein-truncating than missense mutations although similar neurobehavioral profiles were observed.
AB - Background: KAT6A (Arboleda-Tham) syndrome is a Mendelian disorder of the epigenetic machinery caused by pathogenic variants in the lysine acetyltransferase 6 A (KAT6A) gene. Intellectual disability and speech/language impairment (e.g., minimally verbal) are common features of the disorder, with late-truncating variants associated with a more severe form of intellectual disability. However, much of the cognitive phenotype remains elusive given the dearth of research. Participants and methods: This study examined non-verbal and social skills of 15 individuals with molecularly-confirmed diagnoses of KAT6A syndrome (Mean age = 10.32 years, SD = 4.12). Participants completed select subtests from the DAS-II, the NEPSY-II, and the Beery Buktenica Developmental Test of Visual Motor Integration 6th Edition, and their caregivers completed an assortment of behavior rating inventories. Results: Findings suggest global cognitive impairment with nonverbal cognition scores similar to those for receptive language. Autism-related features, particularly restricted interests and repetitive behaviors, and broad adaptive deficits were common in our sample juxtaposed with a relatively strong social drive and low frequency of internalizing and externalizing behavioral problems. A general trend of lower performance scores on nonverbal and receptive language measures was observed among those with protein-truncating variants vs. missense variants; however, no effect was observed on caregiver rating inventories of daily behaviors. Late and early truncating variants yielded comparable neuropsychological profiles. Conclusions: Overall, study results show the cognitive phenotype of KAT6A syndrome includes equally impaired nonverbal cognition and receptive language functioning, paired with relatively intact social drive and strengths in behavior regulation. Emergent genotype-phenotype correlations suggest cognition may be more affected in protein-truncating than missense mutations although similar neurobehavioral profiles were observed.
KW - Behavior
KW - Cognition
KW - Epigenetic
KW - Genetics/Genetic disorders
KW - Histone machinery
KW - KAT6A
KW - Social functioning
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U2 - 10.1186/s13023-024-03175-0
DO - 10.1186/s13023-024-03175-0
M3 - Article
C2 - 38741077
AN - SCOPUS:85192949883
SN - 1750-1172
VL - 19
JO - Orphanet journal of rare diseases
JF - Orphanet journal of rare diseases
IS - 1
M1 - 196
ER -