Sensory Reactivity Symptoms Are a Core Feature of ADNP Syndrome Irrespective of Autism Diagnosis

Abstract

Background: Activity dependent neuroprotective protein (ADNP) syndrome is one of the most common single-gene causes of autism spectrum disorder (ASD) and intellectual disability, however, the phenotypes remain poorly described. Here we examine the sensory reactivity phenotype in children and adolescents with ADNP syndrome. Methods: Twenty-two individuals with ADNP syndrome received comprehensive clinical evaluations including standardized observations, caregiver interviews, and questionnaires to assess sensory reactivity symptoms. Relationships between sensory symptoms and age, sex, ASD, IQ, and adaptive behavior were examined. Genotype-phenotype correlations with the recurrent p.Tyr719* variant were also explored. Results: Sensory reactivity symptoms were observed and reported in all participants. A syndrome-specific phenotype was identified, characterized by high levels of sensory seeking across tactile, auditory, and visual domains. Tactile hyporeactivity, characterized by pain insensitivity, was reported in the majority of participants. Sensory symptoms were identified across individuals regardless of age, sex, IQ, adaptive ability, genetic variant, and most importantly, ASD status. No significant differences were identified between participants with and without the recurrent p.Tyr719* variant on any sensory measure. Conclusions: Sensory reactivity symptoms are a common clinical feature of ADNP syndrome. Quantifying sensory reactivity using existing standardized measures will enhance understanding of sensory reactivity in individuals with ADNP syndrome and will aid in clinical care. The sensory domain may also represent a promising target for treatment in clinical trials.

CHAMP1 disorder is associated with a complex neurobehavioral phenotype including autism, ADHD, repetitive behaviors and sensory symptoms

“…Additionally, regardless of DSM-5 ASD diagnosis, many individuals in our cohort presented with features of ASD. Most individuals, regardless of ASD status, presented with RRBs and sensory symptoms, a finding seen in other genetic NDDs ( 26 , 27 ). Both the SAND and the Sensory Experiences Questionnaire Version 3.0 (SEQ-3.0) indicated that individuals had high levels of sensory-seeking behaviors.…”

Sensory Reactivity Phenotype in Phelan–McDermid Syndrome Is Distinct from Idiopathic ASD

“…Using a comprehensive direct assessment of sensory symptomatology, this study established a distinct sensory reactivity phenotype in children with a PMS, characterized by global hyporeactivity across visual, tactile, and auditory modalities, and to a lesser degree, tactile and auditory sensory seeking. This sensory phenotype is distinct from iASD and other monogenic forms of ASD [ 21 , 30 ] and offers insight into the potential role of SHANK3 deficiency in sensory reactivity. Understanding sensory reactivity abnormalities in PMS in the context of known glutamatergic dysregulation may inform pharmacological treatment approaches.…”

“…The SAND is a clinician-administered observation and corresponding caregiver interview that captures sensory symptoms based on DSM-5 criteria for ASD and is appropriate for individuals with varying levels of ability, including those with few to no words [ 20 ]. The SAND has been used successfully in other genetic forms of autism [ 21 ]; however, it has yet to be examined extensively in PMS. Establishing the utility of the SAND as a clinical outcome measure may have important implications for ongoing clinical trials in PMS.…”

Sensory Processing Phenotypes in Phelan-McDermid Syndrome and SYNGAP1-Related Intellectual Disability

“…Sensory processing, meaning how sensory signals, such as light, sound, touch, taste or smell are perceived, are commonly altered in many neurodevelopmental disorders [ 1 , 2 ]. For example, sensory processing differences have been described in non-syndromic Autism Spectrum Disorders (ASDs) [ 3 ], tic disorders [ 4 ], Fragile X syndrome [ 5 ], attention deficit hyperactivity disorder [ 6 ] and a limited number of syndromic ASDs [ 7 , 8 , 9 , 10 ]. Not surprisingly, the specific sensory phenotypes and distributions of sensory differences vary across diseases.…”