Are important predictors of adverse outcome in children with symptomatic congenital cytomegalovirus infection overlooked in clinical settings?

OBJECTIVE: Congenital cytomegalovirus infection (cCMV) is a common, frequently unrecognized cause of childhood disability. The aim of the present study was to determine the symptoms that raise the suspicion of cCMV, define the neurodevelopmental outcomes, and assess their correlations. METHODS: This longitudinal observational study comprised 78 children with symptomatic cCMV who underwent neuropediatric follow-up for 4 to 17.9 years. RESULTS: Symptoms of central nervous system involvement, hearing/visual impairments, and hepatic involvement were mostly recognized. The average age of disease suspicion was 3.3 months. In terms of outcomes, 10.53% of the children developed complex minor neurological dysfunction and 23.68% developed cerebral palsy. Visual and hearing impairments occurred in 38.16% and 14.47% of patients, respectively. Intellectual disability was present in 30.26% of patients, and epilepsy in 21.05%. Microcephaly and hearing impairment was significantly associated with overall neurodevelopmental outcome. Microcephaly was also associated with poor motor outcomes, hearing impairment, and severe visual impairment. Furthermore, microcephaly and intrauterine growth restriction were significantly associated with poor cognitive outcomes. CONCLUSION: Symptoms that raised the suspicion of cCMV-especially microcephaly, hearing impairment, and intrauterine growth restriction-were important parameters that were associated with outcomes; however, their recognition was often insufficient and/or late.

COVID-19 and the Field of Intellectual and Developmental Disabilities: Where Have We Been? Where Are We? Where Do We Go?

The coronavirus (COVID-19) pandemic has affected, and will continue to affect, every aspect of the intellectual and developmental disabilities (IDD) community. We provide recommendations to (a) support people with IDD and the broader of field of IDD during the course of the pandemic, and (b) place the IDD community in a strong position when the health threats associated with the pandemic abate and post-pandemic social and policy structures are formed.

Novel CAPN1 mutations extend the phenotypic heterogeneity in combined spastic paraplegia and ataxia.

OBJECTIVE: Recessive mutations in the CAPN1 gene have recently been identified in spastic paraplegia 76 (SPG76), a complex hereditary spastic paraplegia (HSP) that is combined with cerebellar ataxia, resulting in an ataxia-spasticity disease spectrum. This study aims to assess the influence of CAPN1 variants on the occurrence of SPG76 and identify factors potentially contributing to phenotypic heterogeneity. METHODS: We screened a cohort of 240 unrelated HSP families for variants in CAPN1 using high-throughput sequencing analysis. We described in detail the clinical and genetic features of the SPG76 patients in our cohort and summarized all reported cases. RESULTS: Six unreported CAPN1-associated families containing eight patients with or without cerebellar ataxia were found in our cohort of HSP cases. These patients carried three previously reported homozygous truncating mutations (p.V64Gfs* 103, c.759+1G>A, and p.R285* ), and three additional novel compound heterozygous missense mutations (p.R481Q, p.P498L, and p.R618W). Lower limbs spasticity, hyperreflexia, and Babinski signs developed in about 94% of patients, with ataxia developing in 63% of cases. In total, 33 pathogenic mutations were distributed along the three reported functional domains of calpain-1 protein, encoded by CAPN1, with no hotspot region. A comparison of gender distribution between the two groups indicated that female SPG76 patients were significantly more likely to present with complicated HSP than male patients (P = 0.015). INTERPRETATION: Our study supports the clinically heterogeneous inter- and intra-family variability of SPG76 patients, and demonstrates that gender and calpain-1 linker structure may contribute to clinical heterogeneity in SPG76 cases.

COVID-19 outcomes among people with intellectual and developmental disability living in residential group homes in New York State.

BACKGROUND: People with intellectual and developmental disabilities (IDD) may be at higher risk of severe outcomes from COVID-19. OBJECTIVE: To describe COVID-19 outcomes among people with IDD living in residential groups homes in the state of New York and the general population of New York State. METHODS: Data for people with IDD are from a coalition of organizations providing over half of the residential services for the state of New York, and from the New York State Department of Health. Analysis describes COVID-19 case rates, case-fatality, and mortality among people with IDD living in residential group homes and New York State through May 28, 2020. RESULTS: People with IDD living in residential group homes were at greater risk of severe COVID-19 outcomes: case rates - 7,841 per 100,000 for people with IDD compared to 1,910 for New York State; case-fatality - 15.0% for people with IDD compared to 7.9% for New York State; and mortality rate - 1,175 per 100,000 for people with IDD compared to 151 per 100,000 for New York State. Differences in cases and mortality rate were confirmed across regions of the state, but case-fatality rate was only higher for people with IDD in and around the New York City region. CONCLUSIONS: COVID-19 appears to present a greater risk to people with IDD, especially those living in congregate settings. A full understanding of the severity of this risk will not be possible until US states begin publicly sharing all relevant data they have on COVID-19 outcomes among this population.

Secondary congenital aphakia.

UNLABELLED: Abstract PURPOSE: We present the clinical, paraclinical and therapeutic features in a patient with secondary congenital aphakia. METHODS: A 2-year-old patient, diagnosed with congenital rubella syndrome including sensorineural deafness, congenital heart disease, intellectual disability, microcephaly, microphthalmia, and congenital cataract, presented to our clinic for the surgical treatment of cataract. RESULTS: During the surgery, the absence of the lens' cortex was observed, hence, the final diagnose was of secondary congenital aphakia. Surgery was then continued with a posterior capsulorhexis and an anterior vitrectomy, deciding to postpone the implantation of the posterior chamber intraocular lens.

[Three cases of human herpesvirus-6 encephalopathy showing hyperperfusion in the acute phase on SPECT].

Brain hypoperfusion observed on single-photon emission computed tomography (SPECT) is a typical finding in the acute phase of human herpesvirus-6 (HHV-6) encephalopathy. However, from 2004 to 2010, we encountered three cases of HHV-6 encephalopathy in which hyperperfusion in the area of the brain lesion was observed on SPECT performed within 48 hours after disease onset. The hyperperfusion in the brain was followed by hypoperfusion in the recovery phase. These cases suggest that hyperperfusion may appear in damaged areas prior to the hypoperfusion that is normally associated with HHV-6 encephalopathy.

Congenital cytomegalovirus infection: new prospects for prevention and therapy.

Cytomegalovirus is the commonest congenital viral infection in the developed world, with an overall prevalence of approximately 0.6%. Approximately 10% of congenitally infected infants have signs and symptoms of disease at birth, and these symptomatic infants have a substantial risk of subsequent neurologic sequelae. These include sensorineural hearing loss, mental retardation, microcephaly, development delay, seizure disorders, and cerebral palsy. Antiviral therapy for children with symptomatic congenital cytomegalovirus infection is effective at reducing the risk of long-term disabilities and should be offered to families with affected newborns. An effective preconceptual vaccine against CMV could protect against long-term neurologic sequelae and other disabilities.

Cochlear implantation in children with congenital cytomegalovirus infection accompanied by psycho-neurological disorders.

CONCLUSION: Cochlear implantation was effective for deaf children with congenital cytomegalovirus (CMV) infection, but their cochlear implant (CI) outcomes were often impaired, depending on the types of CMV-associated psycho-neurological disorders. Evaluation of cognitive development and autistic tendency of implantees might be useful to predict their CI outcomes. OBJECTIVES: To reveal the influence of CMV-associated psycho-neurological disorders on CI outcomes. METHODS: This was a retrospective evaluation of 11 implantees with congenital CMV infection (CMV-CIs) and 14 implantees with autosomal recessive hearing loss (genetic-CIs). RESULTS: Nine of 11 CMV-CIs suffered from psycho-neurological disorders; one from attention deficit hyperactivity disorder, two from pervasive developmental disorder, and six from mental retardation. Aided hearing thresholds with CIs in the two groups did not differ, but two autistic and two mentally retarded CMV-CIs showed significantly low scores in speech discrimination tests. Language-Social (L-S) developmental quotients (DQs) evaluated by the Kyoto Scale of Psychological development were improved after the implantation in both groups, but the postoperative increase of L-S DQs was significantly smaller in the CMV-CIs than that of genetic-CIs. Interestingly, the postoperative L-S and Cognitive-Adaptive (C-A) DQs showed statistically significant correlation in all cases except for two autistic CMV-CIs whose L-S DQs were much lower than those expected from their C-A DQs.