2024-04-182024-04-182024-03-21https://hdl.handle.net/20.500.12503/32756Background: Lysine N-Methyltransferases (KMTs) play a crucial role in regulating chromatin modification. Specifically, deleterious heterozygous variants in Lysine N-Methyltransferase 5B (KMT5B) are linked to intellectual disability (ID) and/or autism spectrum disorder (ASD). Pathogenic variants in several of these genes have been identified in autosomal- dominant or X- linked neurodevelopmental disorders. Additional symptoms include seizures, crossed eyes, flexible joints, and low muscle tone. However, little is known about the effects of the KMT5B mutation on other organ systems as there are fewer than 50 reported cases in the literature. Case Information: This case report follows a 4-year-old male patient seen in the pediatric clinic for a well child visit. Data obtained from the electronic medical records through authorized providers showed the patient was previously diagnosed with a 17p12 deletion, hereditary neuropathy with pressure palsies (HNPP), and KMT5B de Novo mutation. During infancy, the patient had a history of staring off and eye rolling. Developmental delays prompted a genetic evaluation which revealed a maternally inherited 17p12 deletion involving the PMP22 gene, predisposing the patient to hereditary neuropathy with liability to pressure palsies and a de novo pathogenic variant in the KMT5B gene. The KMT5B mutation predisposed the patient to ID and ASD which manifested as missed developmental milestones. At 33 months, the patient began walking and at 36 months the patient exhibited limited speech (only 7-8 words). Additionally, the patient has a history of possible seizure activity, macrocephaly, hypotonia, and possible craniosynostosis although his last head CT scan did not confirm it. Currently, the patient has bilateral eustachian tube dysfunction requiring tympanostomy tube placement, pes planus requiring ankle foot orthotics, and recurrent croup infections with 6 episodes in the last 2 years. The patient is currently monitored by neurology, ENT, physical therapy, and speech therapy and attends special education at his public school. We are in the process of acquiring the patient's follow-up records from the specialty clinic to evaluate the ongoing status of the patient. Conclusions: The influence of the KMT5B mutation on human embryonic development beyond the brain remains poorly understood, as the existing studies emphasize its impact on intellectual disability. Mouse studies of the mutation have implicated its involvement in the embryonic development of organs such as the lungs, liver, heart, skin, and bone. The recurrent croup infections and eustachian tube dysfunction in our patient emphasizes the need to investigate potential developmental consequences in humans. Recurrent croup infections often stem from secondary causes such as congenital and acquired airway abnormalities. We propose that the KMT5B mutation may have contributed to our patient's eustachian tube dysfunction and potentially caused a congenital airway abnormality, increasing susceptibility to croup infections. This case offers unique insights into the potential association of airway and eustachian tube dysfunction with the KMT5B mutation, which is not previously documented. Given the limited number of reported cases and the demonstrated impact on the embryonic development of various organs in mice, further investigation is warranted to comprehensively assess potential complications associated with the KMT5B mutation in humans.enposter