Psychiatric features and variable neurodevelopment outcome in four females with IQSEC2 spectrum disorder.

IQSEC2 is an X-linked gene highly expressed at the excitatory synapses where it plays a crucial role in α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor trafficking and synaptic plasticity. To date, several males and females with severe to profound intellectual disability have been reported harbouring frameshift and nonsense variants in this gene, whereas a milder phenotype has been recognized in females carrying missense pathogenic variants. Here, we report two novel IQSEC2 variants in four females with psychiatric features and otherwise variable cognitive impairment. A female (case 1) with severe verbal language learning disorder and a psychotic episode (precipitated by exposure to anti-contraceptive pill) harboured a de novo pathogenic frameshift variant (c.1170dupG,p.Gln391Alafs*5), whereas the female proband of family 2, displaying severe psychomotor regression and complex psychiatric features carried a missense variant of uncertain significance (c.770G[A,p.Ser257Asn) that was maternally inherited. Skewed X-inactivation was noted in the carrier mother. The maternal aunt, affected by schizophrenia, was found to bear the same IQSEC2 variant. We discuss the variable clinical presentation of IQSEC2 spectrum disorders and the challenging genotype-phenotype correlation, including the possible role of environmental factors as triggers for decompensation. Our report highlights how psychiatric features may be the main clinical presentation in subtle IQSEC2 phenotype, suggesting that the prevalence of IQSEC2 mutations in patients with psychiatric disorders may be underestimated.

The role of Afro-Canadian status in police or ambulance referral to emergency psychiatric services.

OBJECTIVE: This study tested the hypothesis that among patients admitted to a hospital with psychosis, Afro-Canadian patients would be more likely than Euro-Canadian or Asian-Canadian patients to be brought to emergency services by police or ambulance. METHODS: Data on psychotic patients admitted to the psychiatry ward in 1999 were extracted from records of a general hospital in Montreal. Logistic regression models examined the relationship between being Afro-Canadian and being brought to the emergency service by police or ambulance, while controlling for age, gender, marital status, and number of psychotic symptoms. RESULTS: Of the 351 patients with psychosis, 59 percent were Euro-Canadian, 11 percent were Afro-Canadian, and 18 percent were Asian Canadian. Most Afro-Canadian patients in the study were immigrants from the Caribbean and Africa. Being Afro-Canadian was independently and positively associated with police or ambulance referral to emergency services. CONCLUSIONS: Afro-Canadians admitted to the hospital with psychosis are overrepresented in police and ambulance referrals to emergency psychiatric services.