MSL3 Gene, a Rare X-Linked Genetic Mutation

Rare diseases are often caused by gene mutation, but for most of these diseases the cause remains a mystery. Researchers have discovered that mutation in the Male Specific Lethal (MSL) complex responsible for bulk Histone 4 Lysine 16 acetylation (H4K16ac) in flies and mammals, causes an X-Linked syndrome which can affect both sexes. This is a case of a term male infant, delivered by uncomplicated emergency C/S for fetal bradycardia. After birth, he was noted to have hypotonia and abdominal distension. He had a normal cranial ultrasound and metabolic work up. In the first 6 months of age, he had several admissions to the paediatric ward with respiratory infections and feeding issues. He had genetic work up including CGH array and Karyotyping that came back normal. At 10 months of age, he was found to have some developmental delay and a right sided squint. He was reviewed by the neurology team, and after assessment, an underlying neurodevelopmental disorder vs developmental deviation was suspected. At 17 months of age, he was noted to have subtle dysmorphic features (long philtrum, narrow upper lip with some tenting). He was also noted to have a narrow chest wall, mild head lag, low muscle bulk, pectus carniatum and prominence of the chest wall on the right side. He also had slow developmental progression. MRI Brain was unremarkable. At 3 years of age, a diagnosis was made through exome sequencing at centogene. He was found to have a loss of function change in MSL3 gene. The list of rare diseases caused by gene mutation is endless but thanks to researchers worldwide, the diagnosis of these diseases is now made easy. Nearly all diseases are found to have a genetic component. Therefore, patients presenting with hypotonia, developmental delay, intellectual disabilities..etc should always warrant genetic testing.