KAT6 syndromes are rare genetic neurodevelopmental disorders caused by genetic mutations in the KAT6A or KAT6B genes.
KAT6 syndromes are characterized by speech and motor delay, low muscle tone, feeding or gastrointestinal issues, sleep challenges, and vision issues in early childhood. Neurological findings, such as seizures or brain structure differences, are also common. While patients with KAT6A and KAT6B syndromes share many similarities each syndrome also has its own set of unique traits. For example, children with KAT6B are more likely to have distinct skeletal or joint differences, including joint contractures, limb differences, or kneecap abnormalities.
Etiology
KAT6 syndromes are caused by heterozygous pathogenic variants affecting the KAT6A and KAT6B genes. These genes encode for a lysine (K) acetyltransferase 6A/6B that form part of a histone acetyltransferase complex that regulates transcriptional activity and gene expression. Genotype-phenotype correlations suggest that variants affecting the last two exons of the gene (16 and 17) are associated with a more severe phenotype.
Epidemiology
There are currently about 76 patients with the KAT6A mutation reported within scientific medical literature. However, patient organizations are aware of over 300 patients with KAT6A syndrome.
Little is currently known about KAT6B.
Symptoms
The majority of patients present with neonatal hypotonia and feeding difficulties as well as variable developmental delay and intellectual disability. All patients present with language delay/deficits as well. Approximately half of the patients have a cardiac abnormality such as atrial septal defects, ventricular septal defect, patent foramen ovale and/or persistent ductus arteriosus. Other common symptoms include gastroesophageal reflux, constipation, and eye abnormalities (strabismus, amblyopia, and refractory errors). A facial gestalt might be recognized with a broad nasal tip, thin tented upper lip, and bi-temporal narrowing.
Less common symptoms include microcephaly, autism spectrum disorders, sleep disturbances, craniosynostosis, seizures, increased susceptibility to infections, hematological and immunological abnormalities, and bowel obstruction.
Diagnosis
Diagnosis of KAT6 syndromes is confirmed by whole exome or genome sequencing or multi-gene panels including the KAT6A and KAT6B genes. Cases due to copy number variants might be identified by array-comparative genomic hybridization.
Treatment/Management
Current management is symptom-based and requires a multidisciplinary approach. These may include speech and language therapy and augmentative and alternative communication tools. Cardiac evaluation with electrocardiogram and echocardiogram as well as monitoring for gastroesophageal reflux are important. Tube feeding may be required in infants.
Older patients might need long term medication with laxatives. Follow-up should include evaluation of behavioural/social difficulties, complete blood count and immune profile for recurrent infections, and regular assessment of vision. For sleep disorder, study of obstructive apnoea is recommended and melatonin supplementation might be considered.
References
https://www.kat6.org/about-kat6
https://www.orpha.net/en/disease/detail/457193
Learn more about other rare genetic disorders at https://checkrare.com/diseases/congenital-and-genetic-conditions/