Delineation of the clinical profile of CNOT2 haploinsufficiency and overview of the IDNADFS phenotype.

CNOT2 haploinsufficiency underlies a rare neurodevelopmental disorder named Intellectual Developmental disorder with NAsal speech, Dysmorphic Facies, and variable Skeletal anomalies (IDNADFS, OMIM 618608). The condition clinically overlaps with chromosome 12q15 deletion syndrome, suggesting a major contribution of CNOT2 haploinsufficiency to the latter. CNOT2 is a member of the CCR4-NOT complex, which is a master regulator of multiple cellular processes, including gene expression, RNA deadenylation, and protein ubiquitination. To date, less than 20 pathogenic 12q15 microdeletions encompassing CNOT2, together with a single truncating variant of the gene, and two large intragenic deletions have been reported. Due to the small number of affected subjects described so far, the clinical profile of IDNADFS has not been fully delineated. Here we report five unrelated individuals, three of which carrying de novo intragenic CNOT2 variants, one presenting with a multiexon intragenic deletion, and an additional case of 12q15 microdeletion syndrome. Finally, we assess the features of IDNADFS by reviewing published and present affected individuals and reevaluate the clinical phenotype of this neurodevelopmental disorder.

Phenotypes in adult patients with Rett syndrome: results of a 13-year experience and insights into healthcare transition.

BACKGROUND: Rett syndrome is a complex genetic disorder with age-specific manifestations and over half of the patients surviving into middle age. However, little information about the phenotype of adult individuals with Rett syndrome is available, and mainly relies on questionnaires completed by caregivers. Here, we assess the clinical manifestations and management of adult patients with Rett syndrome and present our experience in transitioning from the paediatric to the adult clinic. METHODS: We analysed the medical records and molecular data of women aged ≥18 years with a diagnosis of classic Rett syndrome and/or pathogenic variants in MECP2, CDKL5 and FOXG1, who were in charge of our clinic. RESULTS: Of the 50 women with classic Rett syndrome, 94% had epilepsy (26% drug-resistant), 20% showed extrapyramidal signs, 40% sleep problems and 36% behavioural disorders. Eighty-six % patients exhibited gastrointestinal problems; 70% had scoliosis and 90% low bone density. Breathing irregularities were diagnosed in 60%. None of the patients had cardiac issues. CDKL5 patients experienced fewer breathing abnormalities than women with classic Rett syndrome. CONCLUSION: The delineation of an adult phenotype in Rett syndrome demonstrates the importance of a transitional programme and the need of a dedicated multidisciplinary team to optimise the clinical management of these patients.

Vitamin D deficiency in a population of migrant children: an Italian retrospective cross-sectional multicentric study.

BACKGROUND: Vitamin D is a hot topic in the scientific community. Its deficiency and the implications for the children's health became increasingly discussed during the last 20 years. The main aim of this retrospective study was to determinate the prevalence of vitamin D metabolism disorders in a population of adopted children and their risk factors. METHODS: We gathered data from 2140 children observed in five different National Working Group for the Migrant Children of the Italian Society of Pediatrics centers, variously located in Italy. Serum 25-hydroxy (OH)-D concentration was used to determine every child's vitamin D status, defined as severely deficient (serum 25-OH-D < 10 ng/ml), moderately deficient (serum 25-OH-D {≥10 ng/ml U < 20 ng/ml}), mildly deficient (serum 25-OH-D {≥20 ng/ml U < 30 ng/ml}) and normal (serum 25-OH-D ≥ 30 ng/ml). RESULTS: Mean value of serum 25-OH-D was 22.7 ng/ml (SD ± 12.1). Vitamin D status was deemed as normal in 483 (22.6%) children, mildly deficient in 718 (33.6%) children, moderately deficient in 730 (34.1%) children and severely deficient in 209 (9.8%) children. CONCLUSIONS: A very high percentage of migrant children is affected by hypovitaminosis D, with a strong association with age, geographic origin, season of blood sample collection and time spent in Italy after the arrival. This finding highlights the need for corrective measures. However, these measures cannot be applied without increasing the access of migrant populations to healthcare services.

Italian multicentre study found infectious and vaccine-preventable diseases in children adopted from Africa and recommends prompt medical screening.

AIM: This study evaluated the prevalence of infectious diseases and immunisation status of children adopted from Africa. METHODS: We studied 762 African children referred to 11 Italian paediatric centres in 2009-2015. Clinical and laboratory data were retrospectively collected and analysed. RESULTS: The median age of the children (60.3% males) was 3 years and 6 months, 52.6% came from Ethiopia and 50.1% had at least one infectious disease. Parasitic infections accounted for the majority of the infectious diseases (409 of 715), and the most common were Giardia lamblia (n = 239), Toxocara canis (n = 65) and skin infections (n = 205), notably Tinea capitis/corporis (n = 134) and Molluscum contagiosum (n = 56) Active tuberculosis (TB) was diagnosed in nine children (1.2%). Latent TB infections were diagnosed in 52 (6.8%) children, and only 23 had concordant positive tuberculin skin tests and Quantiferon Gold In-Tube results. Discordant results were associated with Bacille de Calmette-Guérin vaccinations (odd ratio 6.30 and 95% confidence interval of 1.01-39.20, p = 0.011). Nonprotective antitetanus or antihepatitis B antibody titres were documented in 266 (34.9%) and 396 (51.9%) of the 762 children. CONCLUSION: The prevalence of infectious conditions and not-protective titres for vaccine-preventable diseases observed in our population underlines the need for prompt and complete medical screening of children adopted from Africa.