What is a KAT6A-related disorder?
KAT6A-related disorder occurs when there is a change or alteration (like a spelling mistake) to the KAT6A gene, meaning the gene loses or alters its usual function. This results in changes to the usual development patterns in the affected individual.
KAT6A is a gene on the short arm (the ‘p’ arm) of chromosome 8. It is within the band 8p11.21. Whilst the exact function of the KAT6A gene is not yet fully understood, it is part of a group of genes known to affect many body functions. The KAT6A gene makes the KAT6A protein, which then helps to control the production of proteins from other genes. The KAT6A protein is involved in unravelling specific parts of the chromosome so that other proteins can be made. It also modifies proteins once they have been made. Because the KAT6A protein is involved in controlling the expression of many other genes, a variation in the KAT6A gene can cause changes in many different parts of the body. We do not yet fully understand all the functions of the KAT6A gene and protein. 3, 5
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Frequently asked questions
Children with KAT6A variations commonly have intellectual disability, hypotonia (low muscle tone), vision difficulties (including strabismus/crossed-eyes), feeding difficulties, reflux, congenital heart defects, and sleep disturbance. Facial features commonly include microcephaly (small head size), a broad nasal tip that becomes more prominent with age and a thin upper lip.1-3 Behavioural problems and autistic features have been noted. 1,3
Marked speech and language delay is common alongside intellectual disability in individuals with this condition. Many individuals remain non-verbal into adolescence and adulthood, and use alternative means of communication (e.g., picture communication devices, eye gaze). 1,3
Many individuals with KAT6A variants do not rely on verbal communication. However, in those that do use verbal speech, some may not say first words until older than 18 months, and some may not begin combining words until older than 8 years of age.1
In individuals with KAT6A syndrome who are verbal, their speech may be difficult to understand. They usually have more than one speech disorder including speech apraxia (CAS), phonological delay, and phonological disorder.1
There have been no longitudinal studies looking at individuals with KAT6A gene changes over time. Current studies demonstrate that many individuals will continue to have limited or no speech even into adulthood (this can be called "non-verbal" or "minimally-verbal"), while some others develop more functional speech and language despite early significant delays. 1-2
There is no research on speech and language interventions that are specifically designed for individuals with KAT6A gene variations. At present an individualised approach should be taken to assessment and management to ensure therapies are tailored to, and optimised for each child.
Some adults have been reported with functional speech and language despite delays in development earlier in life, however many adolescents still have significant communication challenges throughout life and require alternative means of communication (e.g., picture communication devices, sign language).1-2
In individuals with KAT6A gene variants, there is a spread of speech abilities across the lifespan, just like in childhood. Some remain non-verbal, some may be difficult to understand (e.g. with apraxia), and some may be more easily understood. All individuals have some communication challenges.1
- St John, M., Amor, DJ., Morgan, AT. (2022). Speech and language development and genotype-phenotype correlation in 49 individuals with KAT6A syndrome. American Journal of Medical Genetics - Part A.
- Eising, E., Carrion-Castillo, A., Vino, A., Strand, E. A., Jakielski, K. J., Scerri, T. S., Hildebrand, M. S., Webster, R., Ma, A., Mazoyer, B., Francks, C., Bahlo, M., Scheffer, I. E., Morgan, A. T., Shriberg, L. D. & Fisher, S. E. (2018). A set of regulatory genes co-expressed in embryonic human brain is implicated in disrupted speech development. Molecular Psychiatry, 20(1).
- Kennedy, J., Goudie, D., Blair, E., Chandler, K., Joss, S., McKay, V., Green, A., Armstrong, R., Lees, M., Kamien, B., Hopper, B., Tan, T.Y., Yap, P., Stark, Z., Okamoto, N., Miyake, N., Matsumoto, N., Macnamara, E., Murphy, J.L., McCormick, E., Hakonarson, H., Falk, M.J., Li, D., Blackburn, P., Klee, E., Babovic-Vuksanovic, D., Schelley, S., Hudgins, L., Kant, S., Isidor, B., Cogne, B., Bradbury, K., Williams, M., Patel, C., Heussler, H., Duff-Farrier, C., Lakeman, P., Scurr, I., Kini, U., Elting, M., Rejinders, M., Schuurs-Hoeijmakers, J., Wafik, M., Blomhoff, A., Ruivenkamp, C.A.L., Nibbeling, E., Dingemans, A.J.M., Douine, E.D., Nelson, S.F., DDD Study, Arboleda, V.A., Newbury-Ecob, R. (2019). KAT6A Syndrome: genotype–phenotype correlation in 76 patients with pathogenic KAT6A variants. Genetics in Medicine, 21(4), 850-860.
- Millan, F., Cho, M. T., Retterer, K., Monaghan, K. G., Bai, R., Vitazka, P., Everman, D.B., Smith, B., Angle, B., Roberts, V., Immken, L., Nagakura, H., DiFazio, M., Sherr E., Haverfield, E., Friedman, B., Telegraphi, A., Juusola, J., Chung, W.K., & Bale, S. (2016). Whole exome sequencing reveals de novo pathogenic variants in KAT6A as a cause of a neurodevelopmental disorder. American Journal of Medical Genetics – Part A, 170(7), 1791-1798.
- Tham, E., Lindstrand, A., Santani, A., Malmgren, H., Nesbitt, A., Dubbs, H.A., Zackai, E.H., Parker, M.J., Milan, F., Rosenbaum, K., Wilson G.N., Nordgren, A. (2015). Dominant mutations in KAT6A cause intellectual disability with recognizable syndromic features. American Journal of Human Genetics, 96, 507–13.
- Voss, A. K., Thomas, T. (2009). MYST family histone acetylytransferases take center stage in stem cells and development. Bioessays, 31, 1050-1061.