Behavioural phenotypes and genetic syndromes — structured clinical viva

Define phenotype. Probabilistic association between syndrome and behavioural/psychiatric patterns (Dykens) — not pathognomonic, not exclusive, not a DSM code.^[1]

Five-syndrome comparison. Down (trisomy 21/APP): depression and early Alzheimer risk. Fragile X (FMR1 full mutation greater than 200 CGG): ID, ASD, ADHD, anxiety. PWS (loss of paternal 15q genes): hyperphagia, OCD-like, UPD-linked psychosis. Angelman (maternal UBE3A loss): severe ID, seizures, happy affect, little speech. 22q11.2DS (microdeletion CNV): ADHD/anxiety/ASD traits and high adult psychosis risk.^{[2][3][4][5][7][8]}

PWS UPD psychosis. Boer et al. showed psychotic illness particularly in maternal uniparental disomy PWS — genotype informs risk counselling and vigilance.^[4]

22q11 evidence. Murphy: high schizophrenia rates in adult VCFS. Schneider consortium: multi-disorder burden across ages including psychosis risk rising toward adulthood.^[2][3]

Investigation. Chromosomal microarray first-tier for unexplained developmental disability/congenital anomalies; add FMR1, 15q methylation, and phenotype-driven tests; involve clinical genetics.^[6]

Prescribing. Start low, go slow; treat diagnosed psychosis/depression/ADHD after medical screen; metabolic and cardiac monitoring; food security critical in PWS; avoid diagnostic overshadowing.^[3][8]