Behavioral problems are an important issue for people with CHARGE syndrome. The similarity of their behavioral traits with those of people with autism raises questions. In a large national cross-sectional study, we used specific standardized tools for diagnosing autism (Autism Diagnostic Interview-Revised and Diagnostic and Statistical Manual of Mental Disorders, 5th edition, DSM-5) and evaluating behavioral disorders (Developmental Behavior Checklist-Parents, DBC-P) to investigate a series of individuals with CHARGE syndrome, defined by Verloes\'s criteria. We evaluated their adaptive functioning level and sensory particularities and extracted several data items from medical files to assess as potential risk factors for autism and/or behavioral disorders.
We investigated 64 individuals with CHARGE syndrome (35 females; mean age 10.7 years, SD 7.1 years). Among 46 participants with complete results for the Autism Diagnostic Interview-Revised (ADI-R), 13 (28%) had a diagnosis of autism according to the ADI-R, and 25 (54%) had a diagnosis of autism spectrum disorder (ASD) according to the DSM-5 criteria. The frequency of autistic traits in the entire group was a continuum. We did not identify any risk factor for ASD but found a negative correlation between the ADI-R score and adaptive functioning level. Among 48 participants with data for the DBC-P, 26 (55%) had behavioral disorders, which were more frequent in patients with radiological brain anomalies, impaired adaptive functioning, later independent walking, and more sensory particularities.
ASD should be considered to be an independent risk requiring early screening and management in children born with CHARGE syndrome.

Amyotrophic Lateral Sclerosis and CHARGE syndrome are complex neurological disorders, which never occurred together in the same family and, to date, no putative correlation between them has been described on PubMed Central. Due to our aim was to evaluate the presence of different genetic variants involved in these pathologies, we reported a clinical and genetic description of two sisters affected by these two different disorders. In the CHARGE patient, molecular analysis of the CHD7 gene revealed the c.8016G >A de novo variant in exon 37. The ALS patient had been screened negative for mutations in SOD1, TARDBP, FUS/TLS, C9orf72 and KIF5A genes. Anyway, targeted next generation sequencing analysis identified known and unknown genetic variations in 39 ALS-related genes: a total of 380 variants were reported, of which 194 in the ALS patient and 186 in the CHARGE patient. To date, although the results suggest that the occurrence of the two syndromes in the same family is co-incidental rather than based on a causative genetic variant, we could hypothesize that other factors might act as modulators in the pathogenesis of these different phenotypes.

BACKGROUND: Atopic disorders have been reported in CHARGE syndrome, but the prevalence and underlying mechanisms are not known.
METHODS: We performed a retrospective study of atopic disorders in 23 individuals with CHARGE syndrome, and reviewed other published reports of atopic disorders in CHARGE syndrome. We assayed for enrichment of atopic disorders in CHARGE syndrome based on gender and presence of a CHD7 pathogenic variant.
RESULTS: In our cohort, 65% (15/23) of individuals with CHARGE syndrome were found to have a pathogenic CHD7 variant. Overall, 65% (15/23) of individuals with CHARGE had atopic disorders. Among the 23 individuals with CHARGE, 22% (5/23) had food allergy, 26% (6/23) exhibited drug allergy, 22% (5/23) had contact allergy, 9% (2/23) had allergic rhinitis, and 22% (5/23) had asthma. In our cohort, the proportion of males to females with CHARGE and atopic disorders was 11:4 (P < 0.01), and there was no significant difference between atopic disorders in individuals with CHD7 pathogenic variants and those without CHD7 pathogenic variants (P > 0.05).
CONCLUSIONS: In our cohort of 23 individuals with CHARGE syndrome, 15 (65%) exhibited atopic disorders, with a slight male predominance.