Congenital Zika virus (ZIKV) infection may present with a broad spectrum of clinical manifestations. Some sequelae, particularly neurodevelopmental problems, may have a later onset. We conducted a prospective cohort study of 799 high-risk pregnant women who were followed up until delivery. Eighty-three women and/or newborns were considered ZIKV exposed and/or infected. Laboratory diagnosis was made by polymerase chain reaction in the pregnant mothers and their respective newborns, as well as Dengue virus, Chikungunya virus, and ZIKV serology. Serology for toxoplasmosis, rubella, cytomegalovirus, herpes simplex virus, and syphilis infections were also performed in microcephalic newborns. The newborns included in the study were followed up until their third birthday. Developmental delay was observed in nine patients (13.2%): mild cognitive delay in three patients, speech delay in three patients, autism spectrum disorder in two patients, and severe neurological abnormalities in one microcephalic patient; sensorineural hearing loss, three patients and dysphagia, six patients. Microcephaly due to ZIKV occurred in three patients (3.6%). Clinical manifestations can appear after the first year of life in children infected/exposed to ZIKV, emphasizing the need for long-term follow-up.

Tuberous sclerosis complex (TSC) is an autosomal dominant neurodevelopmental disorder and multisystem disease caused by pathogenic DNA alterations in the TSC1 and TSC2 tumor suppressor genes. A molecular genetic diagnosis of TSC confirms the clinical diagnosis, facilitating the implementation of appropriate care and surveillance. TSC1 and TSC2 encode the core components of the TSC1/2 complex (TSC1/2), a negative regulator of the mechanistic target of rapamycin (MTOR) complex 1 (TORC1). Functional analysis of the effects of TSC1 and TSC2 variants on TORC1 activity can help establish variant pathogenicity. We searched for pathogenic alterations to TSC1 and TSC2 in DNA isolated from 116 individuals with a definite clinical diagnosis of TSC. Missense variants and in-frame deletions were functionally assessed. Pathogenic DNA alterations were identified in 106 cases (91%); 18 (17%) in TSC1 and 88 (83%) in TSC2. Of these, 35 were novel. Disruption of TSC1/2 activity was demonstrated for seven TSC2 variants. Molecular diagnostics confirms the clinical diagnosis of TSC in a large proportion of cases. Functional assessment can help establish variant pathogenicity and is a useful adjunct to DNA analysis.