Neurodevelopmental profile of HIVEP2-related disorder

Abstract

Aim: To characterize the neurodevelopmental profile and systemic features of HIVEP2-related disorder.

Method: This study used retrospective medical history and standardized assessment data from Simons Searchlight to describe the clinical characteristics of 12 individuals (eight males, four females; age range 3y 3mo-12y 8mo; mean age [SD] 7y 7mo [2y 11mo]) with pathogenic HIVEP2 variants, focusing on their levels of adaptive functioning, autism symptomology, and emotional and behavioral characteristics.

Results: Common features included neonatal complications, hypotonia, developmental delay, intellectual disability, language impairment, gastroesophageal reflux, and strabismus. A minority of individuals had epilepsy, microcephaly, or a movement disorder. Based on the Vineland Adaptive Behavior Scales, Second Edition, affected individuals showed impairments in adaptive behavior (mean composite standard score [SD] 56.4 [10.2]; n=8). The cohort also had significant impairments in social problems, as measured by the Social Responsiveness Scale, Second Edition (mean total score [SD] 76.4 [11.3]; n=10) and clinically significant emotional and behavioral difficulties, as measured by the Child Behavior Checklist for ages 6-18 (mean total T score [SD] 66.9 [8.2]; n=8).

Interpretation: These results show that individuals with HIVEP2-related disorder have impairments in adaptive and social-related behaviors as well as difficulties in emotional and behavioral symptoms.

Figure 1:

Schematic of variants in HIVEP2 in the Simons Searchlight project.

Figure 2.

Box-and-whisker plots of (a) the Vineland Adaptive Behavior Scales, Second Edition (VABS-II) standard scores (overall composite and individual subdomains), (b) the Social Responsiveness Scales, Second Edition (SRS-2) T scores (total and individual subscales), (c) the Child Behavioral Checklist for ages 6–18 (CBCL/6–18) T scores for total score, internal broadband scale, and external broadband scale, and (d) CBCL/6–18 T scores for individual syndrome scales in the cohort. The black dot indicates the mean score in each category. VABS-II scores are standardized to a mean of 100 (SD 15). Lower scores indicate greater impairment. For the SRS-2, scores ≤59 are considered normal and higher scores indicate greater impairment. CBCL/6–18 scores are scaled to a mean of 50 (SD 10). Higher scores indicate greater impairment. The mean value for each score is listed, followed by the number of individuals included in the analysis in parentheses. (e) Relationship between autism spectrum disorder symptom severity (SRS-2 total T score) and adaptive functioning (VABS-II composite and subdomain standard scores). Seven individuals had available SRS-2 scores together with VABS-II composite, communication, daily living skills, and socialization scores; only four individuals had available SRS-2 scores together with VABS-II motor scores. DLS, daily living skills.