PERCHING syndrome: Clinical presentation in the first African patient confirmed by clinical whole genome sequencing.

PERCHING syndrome is a rare multisystem developmental disorder caused by autosomal recessive (AR) variants (truncating and missense) in the Kelch-like family member 7 gene (KLHL7). We report the first phenotypic and molecular description of PERCHING syndrome in a patient from Central Africa. The patient presented multiple dysmorphic features in addition to neurological, respiratory, gastroenteric, and dysautonomic disorders. Clinical Whole Genome Sequencing in the proband and his mother identified two novel heterozygous variants in the KLHL7 gene, including a maternally inherited intronic variant (NM_001031710.2:c.793 + 5G > C) classified as Variant of Uncertain Significance and a frameshift stop gain variant (NM_001031710.2:c.944delG; p.Ser315ThrfsTer23) of unknown inheritance classified as likely pathogenic. Although the diagnosis was only evoked after genomic testing, the review of published patients suggests that this disease could be clinically recognizable and maybe considered as an encephalopathy. Our report will allow expanding the phenotypic and molecular spectrum of Perching syndrome.

Williams-Beuren syndrome: pitfalls for diagnosis in limited resources setting.

Patients with Williams-Beuren Syndrome can be recognized clinically, given the characteristic dysmorphism, intellectual disability, and behavior. We report on a Congolese boy with typical WBS facial characteristics. He suffered meningitis and coma at the age of 2 years then subsequently presented with profound intellectual disability and atypical behavior. The WBS was only made at age 8.2 years and confirmed with FISH testing and microarray-CGH. The present report aims to warn clinicians that infections may associate and/or modify a genetic disease as this may be observed in developing countries given the prevalence of infectious diseases.

Neurodevelopmental trajectory of HIV-infected children accessing care in Kinshasa, Democratic Republic of Congo.

OBJECTIVE: To assess the effect of HIV care (including highly active antiretroviral therapy if eligible) on neurodevelopment. DESIGN: Prospective cohort study. METHODS: Motor and mental development of 35 HIV-infected children (aged 18-71 months) was assessed at entry into care and after 6 and 12 months using age-appropriate tools. Developmental trajectory was compared with 35 HIV-uninfected, affected, and 90 control children using linear mixed-effects models. Effects of age (29 months) and timing of entry into care (before or after highly active antiretroviral therapy eligibility) were explored in secondary analyses. RESULTS: At baseline, HIV-infected children had the lowest, control children the highest, and HIV-uninfected affected children intermediate mean developmental scores. After 1 year of care, HIV-infected children achieved mean motor and cognitive scores that were similar to HIV uninfected, affected children although lower compared with control children. Overall, HIV-infected children experienced accelerated motor development but similar gains in cognitive development compared with control children. Exploratory analyses suggest that younger children and those presenting early may experience accelerated greater gains in development. CONCLUSIONS: HIV-infected children accessing care experience improved motor development, and may, if care is initiated at a young age or an early stage of the disease, also experience gains in cognitive development.

Impact of the HIV/AIDS epidemic on the neurodevelopment of preschool-aged children in Kinshasa, Democratic Republic of the Congo.

OBJECTIVES: Pediatric HIV infection is a growing problem in most regions of the world. Data on the effects of HIV on the neurodevelopment of children in resource-poor settings are scarce but necessary to guide interventions. The purpose of this study was to compare the neurodevelopment of preschool-aged HIV-infected, HIV-affected (HIV-uninfected AIDS orphans and HIV-uninfected children whose mother had symptomatic AIDS), and healthy control children in Kinshasa, Democratic Republic of Congo. METHODS: Thirty-five HIV-infected, 35 HIV-affected, and 90 control children aged 18 to 72 months were assessed by using the Bayley Scales of Infant Development II, Peabody Developmental Motor Scales, Snijders-Oomen Nonverbal Intelligence Test, and Rossetti Infant-Toddler Language Scale, as appropriate for age. RESULTS: Overall, 60% of HIV-infected children had severe delay in cognitive function, 29% had severe delay in motor skills, 85% had delays in language expression, and 77% had delays in language comprehension, all significantly higher rates as compared with control children. Young HIV-infected children (aged 18-29 months) performed worse, with 91% and 82% demonstrating severe mental and motor delay, respectively, compared with 46% and 4% in older HIV-infected children (aged 30-72 months). HIV-affected children had significantly more motor and language expression delay than control children. CONCLUSIONS: The impact of the HIV pandemic on children's neurodevelopment extends beyond the direct effect of the HIV virus on the central nervous system. AIDS orphans and HIV-negative children whose mothers had AIDS demonstrated significant delays in their neurodevelopment, although to a lesser degree and in fewer developmental domains than HIV-infected children. Young HIV-infected children were the most severely afflicted group, indicating the need for early interventions. Older children performed better as a result of a "survival effect," with only those children with less aggressive disease surviving.