Sensory Responsiveness Research Articles

1.26 COMPARISON OF GUSTATORY SENSORY OVER-RESPONSIVITY BETWEEN PARENT-REPORT AND DIRECT ASSESSMENT IN A PEDIATRIC COHORT

Sensory overresponsivity, a subtype of sensory processing dysfunction (SPD), affects children with and without neurodevelopmental disorders. The Sensory Processing-Three Dimensions: Assessment (SP-3D:A, for estimating SP3D) is a structured performance-based measure to phenotype SPD. To date, there is a paucity of research about gustatory overresponsivity (GOR). This study aims to compare GOR using a direct measure (SP-3D:A) and a parental report (Short Sensory Profile [SSP]) in a pediatric cohort.

The child sensorium as privileged biopolitical resource: Sensory care and the burden of emotional control in middle class North American childhood

This article draws on ethnographic and archival material to examine a contemporary, neuroscience informed politics of care focused on the child sensorium (understood as an embodied neurobiological endowment and material and political resource). I frame care-taking practices focused on children’s sensory endowment, responsivity, and difference as a form of biopolitical regulation in which children, parents, therapists, and educators are implicated. As such, I examine how such care intersects with political, economic, and educational forces and circumstances that differentiate North American childhoods and reconfigure expectations of children and parents. In the process, I relate medicalized sensory difference to shifting skill demands for children that emphasize emotional control in public and educational contexts. Moreover, I highlight how privileged parental engagements with scientific knowledge and practices of therapeutic care focused on children’s sensory endowments and difference articulate with these new skill demands but also deploy embodied sensorial–neurological difference/neurodiversity as a means to transform dynamics of stigma and control within children’s and families’ lives and educational contexts. At the same time, I show how attempts to cultivate sensory capacities and engagements with medicalized sensory difference are implicated in broader biopolitical dynamic of exclusion that unevenly recognizes difference/disability.

The Secretomes of Painful Versus Nonpainful Human Schwannomatosis Tumor Cells Differentially Influence Sensory Neuron Gene Expression and Sensitivity

Schwannomatosis is a multiple tumor syndrome in which patients develop benign tumors along peripheral nerves throughout the body. The first symptom with which schwannomatosis patients often present, prior to discovery of tumors, is pain. This pain can be debilitating and is often inadequately alleviated by pharmacological approaches. Schwannomatosis-associated pain can be localized to the area of a tumor, or widespread. Moreover, not all tumors are painful, and the occurrence of pain is often unrelated to tumor size or location. We speculate that some individual tumors, but not others, secrete factors that act on nearby nerves to augment nociception by producing neuronal sensitization or spontaneous neuronal firing. We created cell lines from human SWN tumors with varying degrees of pain. We have found that conditioned medium (CM) collected from painful SWN tumors, but not that from nonpainful SWN tumors, sensitized DRG neurons, causing increased sensitivity to depolarization by KCl, increased response to noxious TRPV1 and TRPA1 agonists and also upregulated the expression of pain-associated genes in DRG cultures. Multiple cytokines were also detected at higher levels in CM from painful tumors. Taken together our data demonstrate a differential ability of painful versus non-painful human schwannomatosis tumor cells to secrete factors that augment sensory neuron responsiveness, and thus identify a potential determinant of pain heterogeneity in schwannomatosis.

Update of a Meta-analysis of Sensory Symptoms in ASD: A New Decade of Research

This meta-analysis updated evidence regarding sensory over-responsivity (SOR), under-responsivity (SUR) and seeking symptoms in individuals with autism spectrum disorders (ASDs) relative to typical controls and those with other conditions. Fifty-five questionnaire studies included 4606 individuals with ASD. Moderators tested were age, IQ, male ratio, matching group, and self-report. Compared to typical controls, effect size was large and significant for SOR, SUR, and Seeking but heterogeneous. For Seeking, age, IQ and self-report were significant moderators. Compared with developmental disorders (DDs) groups, effect size was significantly positive for SOR and Seeking; whereas compared with other clinical groups, only SOR was significant. These findings highlight the core nature of sensory symptoms in ASD and particularly SOR. Explanatory factors are yet to be revealed.

Sensory Over-Responsivity as an Added Dimension in ADHD.

Years of research have added to our understanding of Attention Deficit Hyperactivity Disorder (ADHD). None-the-less there is still much that is poorly understood. There is a need for, and ongoing interest in, developing a deeper understanding of this disorder to optimally identify risk and better inform treatment. Here, we present a compilation of findings examining ADHD both behaviorally and using neurophysiologic markers. Drawing on early work of McIntosh and co-investigators, we examined response to sensory challenge in children with ADHD, measuring HPA activity and electrodermal response (EDR) secondary to sensory stressors. In addition, we have examined the relationship between these physiologic measures, and reports of behavioral sensory over-responsivity and anxiety. Findings suggest that sensory responsivity differentiates among children with ADHD and warrants consideration. We link these findings with research conducted both prior to and after our own work and emphasize that there a growing knowledge supporting a relationship between ADHD and sensory over-responsivity, but more research is needed. Given the call from the National Institute of Health to move toward a more dimensional diagnostic process for mental health concerns, and away from the more routine categorical diagnostic process, we suggest sensory over-responsivity as a dimension in the diagnostic process for children with ADHD.

Acute/Subacute and Sub-Chronic Oral Toxicity of a Hidroxytyrosol-Rich Virgin Olive Oil Extract.

The objective of this study was to determine the acute (one single dose), subacute (14 days), and sub-chronic (90 days) toxicity of an aqueous virgin olive oil (VOO) extract rich in hydroxytyrosol in rats. For acute/subacute toxicity, rats were divided into three groups. The control group received distilled water (n = 9), another experimental group received a single dose of 300 mg/kg (n = 3), and a third group received one dose of 2000 mg/kg (n = 4) during 14 days. The sub-chronic study included 60rats distributed in three groups (n = 20: 10 males and 10 females) receiving daily different three doses of the VOO extract in the drinking water during 90 days: (1) 100 mg/kg, (2) 300 mg/kg, and (3) 1000 mg/kg. In parallel, a fourth additional group (n = 20: 10 males and 10 females) did not receive any extract (control group). Clinical signs, body weight, functional observations of sensory and motor reactivity, hematological and biochemical analyses, and macroscopic and microscopic histopathology were evaluated. No adverse effects were observed after the administration of the different doses of the hydroxytyrosol-rich VOO extract, which suggests that the enrichment of VOO in its phenolic compound is safe, and can be used as functional foods for the treatment of chronic degenerative diseases.

Thermal Perceptual Thresholds are typical in Autism Spectrum Disorder but Strongly Related to Intra-individual Response Variability

Individuals with autism spectrum disorder (ASD) are often reported to exhibit an apparent indifference to pain or temperature. Leading models suggest that this behavior is the result of elevated perceptual thresholds for thermal stimuli, but data to support these assertions are inconclusive. An alternative proposal suggests that the sensory features of ASD arise from increased intra-individual perceptual variability. In this study, we measured method-of-limits warm and cool detection thresholds in 142 individuals (83 with ASD, 59 with typical development [TD], aged 7–54 years), testing relationships with diagnostic group, demographics, and clinical measures. We also investigated the relationship between detection thresholds and a novel measure of intra-individual (trial-to-trial) threshold variability, a putative index of “perceptual noise.” This investigation found no differences in thermal detection thresholds between individuals with ASD and typical controls, despite large differences between groups in sensory reactivity questionnaires and modest group differences in intra-individual variability. Lower performance IQ, male sex, and higher intra-individual variability in threshold estimates were the most significant predictors of elevated detection thresholds. Although no psychophysical measure was significantly correlated with questionnaire measures of sensory hyporeactivity, large intra-individual variability may partially explain the elevated psychophysical thresholds seen in a subset of the ASD population.

Sensory Features in Autism Spectrum Disorder (ASD)—Core Characteristic or Comorbid Factor?

Abstract Date Presented 04/06/19 There has been a lasting debate over whether sensory features are a core characteristic or comorbid phenomenon of ASD. This study explores whether sensory reactivity (hyper and hypo reactivity) may be a distinguishing characteristic of ASD. Understanding these phenotypic characteristics of ASD can help inform personalized OT intervention for sensory features as well as aid in early diagnosis. Primary Author and Speaker: Carly Rosenthal Additional Authors and Speakers: Roseann Schaaf, Rachel Dumont, Rachel Kim, Margaret Ryan, Lauren Santoro, Taylor Sivori Contributing Authors: Judith Ross

Sensory Profiles, Functional Magnetic Resonance Imaging, and Temporal Binding Windows: A Comparison of Data of Autistic Individuals

Abstract Date Presented 04/04/19 This study examined sensory profile scores of 17 individuals with autism spectrum disorder and 15 neurotypical individuals’ sensory profile scores compared to temporal binding window and functional magnetic resonance imaging data to determine a relationship. There were significant differences between groups that could guide treatments for autism. This benefits OTs to assist individuals to overcome the neuronal deficits impacting sensory and behavioral responsiveness. Primary Author and Speaker: Kelsey Long Additional Authors and Speakers: Amy Kurowski-Burt Contributing Authors: Paula Webster, James Lewis

Sensory Processing Predicts Social Responsiveness in Adults With Autism

Abstract Date Presented 04/04/19 This study evaluated the relationship between sensory processing and social responsiveness in young adults with ASD and age-matched neurotypical controls. Compared to controls, young adults with ASD had significant differences on all four quadrants of the sensory profile. However, low registration and sensory gating (the ability to filter irrelevant information) appear to be key predictors of social responsiveness. Primary Author and Speaker: Jewel Crasta Additional Authors and Speakers: Patricia Davies Contributing Authors: William Gavin

Sensory Modulation Disorder (SMD) and Pain: A New Perspective.

Sensory modulation disorder (SMD) affects sensory processing across single or multiple sensory systems. The sensory over-responsivity (SOR) subtype of SMD is manifested clinically as a condition in which non-painful stimuli are perceived as abnormally irritating, unpleasant, or even painful. Moreover, SOR interferes with participation in daily routines and activities (Dunn, 2007; Bar-Shalita et al., 2008; Chien et al., 2016), co-occurs with daily pain hyper-sensitivity, and reduces quality of life due to bodily pain. Laboratory behavioral studies have confirmed abnormal pain perception, as demonstrated by hyperalgesia and an enhanced lingering painful sensation, in children and adults with SMD. Advanced quantitative sensory testing (QST) has revealed the mechanisms of altered pain processing in SOR whereby despite the existence of normal peripheral sensory processing, there is enhanced facilitation of pain-transmitting pathways along with preserved but delayed inhibitory pain modulation. These findings point to central nervous system (CNS) involvement as the underlying mechanism of pain hypersensitivity in SOR. Based on the mutual central processing of both non-painful and painful sensory stimuli, we suggest shared mechanisms such as cortical hyper-excitation, an excitatory-inhibitory neuronal imbalance, and sensory modulation alterations. This is supported by novel findings indicating that SOR is a risk factor and comorbidity of chronic non-neuropathic pain disorders. This is the first review to summarize current empirical knowledge investigating SMD and pain, a sensory modality not yet part of the official SMD realm. We propose a neurophysiological mechanism-based model for the interrelation between pain and SMD. Embracing the pain domain could significantly contribute to the understanding of this condition’s pathogenesis and how it manifests in daily life, as well as suggesting the basis for future potential mechanism-based therapies.

Behavioral response to tactile stimuli relates to brain response to affective touch in 12-month-old infants.

Affective touch activates a brain network responsible for processing social-emotional stimuli in infants, children, and adults, with a core node in the superior temporal sulcus (STS). STS is known to be a region highly susceptible to individual variability, including for tactile stimuli processing. However, little is known about how this region is recruited to process affective touch in infancy. The aim of this study was to examine brain activity to affective touch in the temporal region (STS) and understand if it relates to behavioral patterns of sensory-over responsivity (SOR) to touch. Twelve-month-old infants (n=24) were given affective and discriminative stimuli to the forearm while they were watching a silent movie. Brain activation was recorded in the STS for measures of oxy-hemoglobin (HbO2 ) and deoxy-hemoglobin (Hbb) using functional near infra-red spectroscopy (fNIRS). Aversive responses to tactile stimuli were measured using the Infant-Toddler Sensory Profile. A significant hemodynamic response increase in HbO2 to affective touch was observed in the STS for infants with less aversive behavioral responses to tactile stimuli. The findings suggest that brain activity in the STS for affective touch might be related to individual differences in the affective reaction toward touch.

Distinct Patterns of Neural Habituation and Generalization in Children and Adolescents With Autism With Low and High Sensory Overresponsivity.

Sensory overresponsivity (SOR), an atypical negative reaction to sensory stimuli, is highly prevalent in autism spectrum disorder (ASD). Previous work has related SOR to increased brain response in sensory-limbic regions. This study investigated where these atypical responses fall in three fundamental stages of sensory processing: arousal (i.e., initial response), habituation (i.e., change in response over time), and generalization of response to novel stimuli. Different areas of atypical response would require distinct intervention approaches. Functional MRI was used to examine these patterns of neural habituation to two sets of similar mildly aversive auditory and tactile stimuli in 42 high-functioning children and adolescents with ASD (21 with high levels of SOR and 21 with low levels of SOR) and 27 age-matched typically developing youths (ages 8-17). The relationship between SOR and change in amygdala-prefrontal functional connectivity across the sensory stimulation was also examined. Across repeated sensory stimulation, high-SOR participants with ASD showed reduced ability to maintain habituation in the amygdala and relevant sensory cortices and to maintain inhibition of irrelevant sensory cortices. These results indicate that sensory habituation is a dynamic, time-varying process dependent on sustained regulation across time, which is a particular deficit in high-SOR participants with ASD. However, low-SOR participants with ASD also showed distinct, nontypical neural response patterns, including reduced responsiveness to novel but similar stimuli and increases in prefrontal-amygdala regulation across the sensory exposure. The results suggest that all children with autism have atypical brain responses to sensory stimuli, but whether they express atypical behavioral responses depends on top-down regulatory mechanisms. Results are discussed in terms of targeted intervention approaches.

Repetitive transcranial magnetic stimulation recovers cortical map plasticity induced by sensory deprivation due to deafferentiation.

Key points Partial sensory deprivation (deafferentation) by removing whiskers from the rat snout resulted in a reduced responsiveness of related cortical representations.Repetitive transcranial magnetic stimulation (three blocks of intermittent theta‐burst) applied for 5 days in combination with sensory exploration restored the normal responsiveness level of the deafferented barrel cortex.However, intracortical inhibition (lateral and recurrent) appeared to be reduced after repetitive transcranial magnetic stimulation, probably as the cause of improved responsiveness.Repetitive transcranial magnetic stimulation also reduced the asymmetry of the lateral spread of sensory activity. Repetitive transcranial magnetic stimulation (rTMS) modulates human cortical excitability. It has the potential to support recovery to normal cortical function when the excitation–inhibition balance is altered (e.g. after a stroke or loss of sensory input). We tested cortical map plasticity on the basis of sensory responses (local field potentials, LFPs) and expression of neuronal activity marker proteins within the barrel cortex of rats receiving either active or sham rTMS after selective unilateral deafferentation by whiskers plucking. Rats received daily rTMS [intermittent theta‐burst (iTBS), active or sham] for 5 days before exploring an enriched environment. Our previous studies indicated a disinhibitory effect of iTBS on cortical activity. Therefore, we also expected disinhibitory effects if deafferentation causes depression of sensory responses. Deafferentation resulted in an acute general reduction of sensory responsiveness and enhanced expression of inhibitory activity markers (GAD67, parvalbumin) in the deafferented hemisphere. Active but not sham‐iTBS‐rTMS normalized these measures. The stronger caudal‐to‐frontal horizontal spread of activity across barrels was reduced after deafferentation but not restored after active iTBS, despite generally increased responses. Fitting the LFP data with a computational model of different strengths and types of excitatory and inhibitory connections further revealed an iTBS‐induced reduction of lateral and recurrent inhibition as the most probable scenario. Whether the disinhibitory effect of iTBS for the restoration of normal cortical function in the acute phase of depression after deafferentiation is also beneficial in humans remains to be demonstrated. As recently discussed, disinhibition appears to be required to open a window for neuronal plasticity.

Co-occurrence of Sensory Overresponsivity with Obsessive-Compulsive Symptoms in Childhood and Early Adolescence.

Sensory overresponsivity (SOR) is characterized by challenges in integrating and responding to everyday sensory experiences. Obsessive-compulsive disorder (OCD) is characterized by intrusive thoughts, ritualistic behaviors, and sensory phenomena. There is some evidence that individuals with co-occurring symptoms of SOR and OCD experience more severe anxiety than those with symptoms of OCD alone, but most studies employed small numbers of participants (typically with an OCD diagnosis) assessed at a single time point. Our 2-fold objective was to replicate previous research showing an association between OCD symptoms and SOR symptoms concurrently and to extend these analyses longitudinally in a large, birth-register-based sample. Twins (N = 1613) and their primary caregivers participated in a multimodal, multimethod, longitudinal study. Primary caregivers completed the SOR inventory for their offspring at the age of 8 years, and twins completed the adult sensory profile at the age of 13 years. Parents completed the OCD module of the Diagnostic Interview Schedule for Children-IV when twins were 8 years; twins completed the same module at 13 years. Linear regression models tested for the concurrent and longitudinal associations between SOR and OCD controlling for socioeconomic status. Concurrently, participants' likelihood of exhibiting OCD symptoms increased with each symptom of tactile or auditory overresponsivity at 8 years and 13 years (odds ratio = 1.1-2.7). However, SOR measured at age 8 years was unrelated to adolescent OCD symptoms at 13 years and vice versa. SOR symptoms, although significantly related to concurrent OCD symptoms, do not appear to precede OCD symptoms, suggesting that SOR symptoms may reflect another type of OCD sensory phenomenon rather than a comorbid condition.

DOZ047.50: Patterns of sensory processing in children with esophageal atresia

Abstract Esophageal atresia (EA) is a congenital anomaly requiring neonatal surgery, medical treatment, extended hospitalization, and rehabilitation. Occupational therapists offer a unique perspective on the sensory aspects of behavior. From a sensory processing and integrative perspective, the behaviors are related either to generate or avoid sensory stimulation. Determining the child's threshold for tolerating sensory stimuli helps families and professionals to understand the child's reaction to life experiences additionally help to develop skills such as learning, attention, and somatosensory awareness of the body. The aim of this study is to assess and compare the sensory responses of children with EA and typically developing children (TDC). Sensory Profile is a parent-reporting measure, which assesses children's sensory responses in daily life. Parents response the frequency of their child responds to 125 commonly occurring experiences. Items assess eight categories: auditory, visual, activity level, taste/smell, body position, movement, touch, and emotional/social and nine factors as sensory seeking, emotional reactive, low endurance/tone, oral sensory sensitivity, inattention/distractibility, poor registration, sedentary, fine motor/perceptual. The measure is determined by a Likert scale. Parents of 12 children (5.60 ± 2.07 years/min: 3; max: 8) with EA and parents of 12 TDC (4.23 ± 1.14 years/min: 3; max: 8) matched by age and gender completed the Sensory Profile. The results were analyzed with the SPSS 18. Children with EA differed significantly from TDC children in their sensory responsiveness based on Sensory Profile results in the areas of auditory, tactile, vestibuler, taste and smell processing (P < 0.05) and sensory seeking, emotional reactive, low endurance/tone, oral sensory sensitivity, inattention/distractibility, poor registration factors (P < 0.05). The Sensory Profile can contribute to diagnostic and rehabilitation planning processes and increase understanding of the nature of sensory problems of children with EA. Further studies should be designed with extended groups to generate the results and the effects of interdisciplinary rehabilitation programmes including sensory- based occupational therapy must be analyzed on children diagnosed with EA.

Differentiating between sensory sensitivity and sensory reactivity in relation to restricted interests and repetitive behaviours.

Recent studies have suggested that individuals who exhibit heightened sensitivity also exhibit higher rates and severity of restricted interests and repetitive behaviours. This line of research has been conducted almost exclusively through caregiver reports of sensitivity. Here, a more rigorous psychophysics paradigm was applied to assess sensory sensitivity and relate hypersensitivity to restricted interests and repetitive behaviours. In addition, commonly used questionnaire measures of sensory sensitivity were collected to determine if self-reported measures accurately reflect behavioural measures of sensory sensitivity. In all, 90 typically developing participants completed a visual detection task, a questionnaire measure of sensory processing and a measure of restricted interests and repetitive behaviours. Visual sensitivity, measured both behaviourally and with questionnaires, is positively related to restricted interests and repetitive behaviours. Surprisingly, visual sensitivity as measured behaviourally and through self-report are unrelated. Furthermore, a regression analysis suggests that while restricted interests and repetitive behaviours can be predicted based on both behavioural and self-reported sensitivity, these two predictors account for different portions of the variance in restricted interests and repetitive behaviours. Thus, while these results provide evidence supporting the contribution of sensory sensitivity to restricted interests and repetitive behaviours, these results also indicate that behavioural and questionnaire measures of sensory sensitivity are measuring two distinct constructs. We hypothesize that behavioural measures are measuring sensory sensitivity, while questionnaires measures are in fact measuring sensory reactivity.

A double-blind, placebo-controlled, randomised-designed GABA tea study in children diagnosed with autism spectrum conditions: a feasibility study clinical trial registration: ISRCTN 72571312

ABSTRACT Objective: The research has shown an association with sensorimotor integration and symptomology of Autism Spectrum Conditions (ASC). Specific areas of the brain that are involved in sensorimotor integration, such as the cerebellum and basal ganglia, are pathologically different in individuals with ASC in comparison to typically developing (TD) peers. These brain regions contain GABAergic inhibitory neurons that release an inhibitory neurotransmitter, γ-Aminobutyric acid (GABA). Brain GABA levels are decreased in ASC. This study explored the effect of introducing a non-invasive GABA substitute, in the form of GABA Oolong tea, on sensorimotor skills, ASC profiles, anxieties and sleep of children with ASC. Methods: Nine children took part: (5 male, 4 female). Each child participated in three tea conditions: high GABA, high L-Theanine (a compound that increases GABA), placebo with low GABA. A double-blind, repeated measures design was employed. Measures were taken after each tea condition. Sensory and ASC profiles were scored using parental questionnaires. Motor skills were assessed using a gold standard coordination assessment. Sleep was monitored using an actiwatch and anxiety measured through cortisol assays. Subjective views were sought from parents on ‘best’ tea. Results: The results showed significant improvement in manual dexterity and some large individual improvements in balance, sensory responsivity, DSM-5 criteria and cortisol levels with GABA tea. Improvements were also seen in the L-Theanine condition although they were more sporadic. Conclusions: These results suggest that sensorimotor abilities, anxiety levels and DSM-5 symptomology of children with ASC can benefit from the administration of GABA in the form of Oolong tea.

Sensory Overresponsivity as a Predictor of Amplitude Discrimination Performance in Youth with ASD

Previous studies have suggested that sensory overresponsivity in youth with autism spectrum disorder (ASD) may be due to a failure to habituate to stimuli. We examined the relationship between performance on three tactile psychophysical tasks and the construct of sensory overresponsivity in children with and without ASD. Sensory overresponsivity predicted amplitude discrimination with an adapting stimulus, as well as the effect of adaptation, for ASD youth. Results replicate previous research that children with ASD are less affected by the presence of an adapting stimulus as compared to typically developing children, and further suggest that sensory overresponsivity may be the mechanism underlying the observed lack of an adaptation effect in children with ASD.

An exploratory study of parent-child association in sensory modulation disorder involving ADHD-related symptoms.

Sensory modulation disorder (SMD) and attention deficit hyperactivity disorder (ADHD) can co-occur and have overlapping symptoms, thus challenging practitioners. This study aimed to phenotypically explore parent-child associations in SMD, and the interplay between SMD- and ADHD-related symptoms in children with SMD and their parents. A cross-sectional study examined 70 parents (n = 35 mothers; n = 35 fathers) and their 35 children with and without SMD, aged 4-6 years. Parents completed care-giver reports: The Short Sensory Profile (SSP) and the ADHD Rating Scale, and self-reports: The Sensory Responsiveness Questionnaire (SRQ) and the ADHD Self-Report Scale (ASRS). In the entire sample, we found a mother-offspring correlation between SSP and SRQ-Aversive scores (rs = -0.68; p < 0.001), but no such father-offspring correlation. However, when testing the ADHD Rating Scale and ASRS scores, we found correlations between mothers and offspring (rs = 0.54, p = 0.0008), and between fathers and offspring (rs = 0.34, p = 0.0494). In the entire sample a high correlation was found between SSP and ADHD Rating Scale scores (rs = -0.837, p < 0.001). We further found a high correlation in mothers (rs = 0.70, p < 0.001), and a moderate correlation in fathers (rs = 0.40, p = 0.019) between SRQ-Aversive and ASRS scores. Novel findings reveal that parents-offspring heritability patterns differ in both these related conditions. These may contribute to familial practice and research.