[TS1-4D-2] Neurogenetics: How to apply genetic tests
The advancement in genetic testing methodology has revolutionized the clinical practice particularly in the diagnostic algorithm, and the research in identifying genes responsible for neurogenetic disorders. Prerequisites before genetic testing can be applied efficiently include detailed clinical evaluation and precise definition of neurologic problems with the help of neurophysiologic testing, neuroradiologic testing, and multidisciplinary assessment. If a clinical diagnosis is strongly suspected specific genetic analysis should be done, e.g. Fluorescent in Situ Hybridization (FISH) for patients with microdeletion syndromes such as William syndrome, methylation studies for Prader Willi syndrome/Angelmann syndrome. In patients with chronic encephalopathy or cognitive delay, karyotyping or SNP microarray is indicated if the affected individual also has growth delay, dysmorphic features or organ malformation. Multi-gene panels using next generation sequencing have been increasingly performed to identify the underlying cause of various neurogenetic problems such as intractable epilepsy, dystonia or movement disorders, autistic spectrum disorders, mental retardation, microcephaly/macrocephaly, brain malformation,, myopathy or muscular dystrophies, neuropathy, hearing loss and retinitis pigmentosa. Biochemical genetic testing such as lactate, ammonia, amino acids, organic acids, acylcarnitine, neurotransmitters and etc. should be performed particularly in a patient presented with acute encephalopathy prior to any therapeutic interventions. In certain neurodegenerative disorders such as lysosomal disorders, enzymatic confirmation is needed to arrive at a final diagnosis. Lastly, whole exome sequencing may be useful in diagnosis of difficult neurogenetic cases.