Inside out: Behavioral phenotyping in genetic syndromes - Supplemental materials Chapter 2

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1

Supplemental materials Chapter 2

Self-Injurious Behavior, Neurosci Biobehav Rev 2018; 84:483-491

Appendix II Results

2 Figure S1 Study flow diagram

2 Table S1 Summary data of all included studies

2 Angelman Syndrome

4 Cornelia de Lange Syndrome

5 Cri du Chat Syndrome

11 Down Syndrome

13 fragile X Syndrome

20 Lesch-Nyhan Syndrome

25 Lowe Syndrome

35 Prader-Willi Syndrome

36 Rett Syndrome

44 Smith-Magenis Syndrome

46 Tuberous Sclerosis Syndrome

50 William-Beuren Syndrome

52 ID of unknown origin

53 ID of unknown origin and ASD

69 Others

71 Legend

78 General abbreviations

78 Abbreviations assessment tools

79

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2 Appendix II Results

Figure S1. Study flow diagram

Full text of

manuscripts

assessed for

eligibility (n=80)

Potentially relevant

manuscripts

identified through

database searching

(n=1288)

Manuscripts

screened using

abstracts (n=1155)

Manuscripts excluded as no

ID population, no focus on

SIB, or no original study

(n=714)

Full text of

manuscripts

assessed for

eligibility (n=441)

Manuscripts excluded as no

original study or no focus on

SIB (n=352)

Manuscripts

included for scoping

review (n=169)

Manuscripts excluded as not

related to study objectives

(n=133)

Reference checking

for relevant

manuscripts(n=441)

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3 Appendix II Results

Table S1. Summary data of all included studies

Summary data are presented on Angelman Syndrome (AS), Cornelia de Lange Syndrome (CdLS), Cri du Chat

Syndrome (CdCS), Down Syndrome (DS), fragile X Syndrome (fraX), Lesch-Nyhan Syndrome (LNS), Lowe

syndrome (LS), Prader-Willi Syndrome (PWS), Rett Syndrome (Rett), Smith-Magenis Syndrome (SMS),

Tuberous Sclerosis Syndrome (TSC), William-Beuren Syndrome (WBS), ID of unknown origin, and those with

ID of unknown origin and ASD.

The table explains: general study information (author, year, aim and study method), characteristics of study

population (entity, acquisition, selection criteria, confirmation od the genetic diagnosis, physical

characteristics, and number, age and gender of participants), studied features behavior/cognition (including

assessment and level of abilities), SIB (definition, prevalence, phenomenology) and study appraisal (type of

publication, study design and follow-up).

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4

Angelman

General

Author / year Arron / 20111

Type of study1 _Behavioral

Aim Phenomenology

Methods Questionnaires

Study population

Entity Various known syndromes / Angelman S Acquisition Support group

Selection criteria ID + known syndrome (AS) Confirmation diagnosis n.m.

Physical exams Questionnaire

Results Disturbed vision 12.5%, hearing loss 0%

n 104

Age: mean/SD/range 13.40/7.97/? Male : Female 58:46 Behavior / Cognition

Studied features SIB, repetitie behavior,

hyperactivity/impulsivity, mood, ASD, abilities Assessment (SIB/other behavior/abilities) RBQ, TAQ, MIPQ, ASQ, Wessex

Level of abilities (ID/AF) All levels SIB

Definition Operational (RBQ)

Prevalence 45%

Age of onset n.m.

Provocative influences n.m.

Form(s)/topography2 _{OR: Hits self with body 0.83; hits self against}

object 1.60; hits self with object 2.94; bites self 0.92; pulls self 0.96; rubs/scratches self 0.91; inserts 1.26

Duration n.m.

Frequency n.m.

Intensity n.m.

Severity n.m.

SIB related results Behavioral

Physical

SIB less in AS than in CdCS, CdLS, fraX, PWS, LS and SMS.

SIB associated with repetitive and impulsive behavior.

n.m. Study appraisal

Type pub Original

Study design Cross sectional

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5

CdLS

General

Author / year Arron / 20111 _{Basile / 2007}2 _{Berney / 1999}3

Type of study1 _Behavioral _Behavioral _Behavioral

Aim Phenomenology Behavioral phenotype Behavioral phenotype Methods Questionnaires Direct assessment (hospital) Questionnaire Study population

Entity Various known syndromes / CdLS CdLS CdLS

Acquisition Support groups Support group Support group, prospected by physicians Selection criteria ID + known syndrome (CdLS) None n.m.

Confirmation diagnosis n.m. Clinical Clinical

Physical exams Questionnaire Clinical phenotype severity score Clinical phenotype severity score Results Disturbed vision 23.7%, hearing loss 34% 36/56 classical; 20/56 mild 30/49 classical; 19/49 mild

seizures 14/49; disturbed sleep 39/49; GI problems 37/49

n 101 56 49

Age: mean/SD/range 17.49/17.49/? 10.6/8.5/1-31 10.2/ 7.8/?

Male : Female 41:60 29:27 21:28

Behavior / Cognition

Studied features SIB, repetitive behavior,

hyperactivity/impulsivity, mood, ASD, abilities SIB, challenging behavior, ASD, adaptive behavior, cognition SIB, aggression, hyperactivity, ASD Assessment (SIB/other behavior/abilities) RBQ, TAQ, MIPQ, ASQ, Wessex ABC, DBC-P, VABS, CARS, Wechsler, Leiter-R,

Standford-Binet, Griffiths SSBPQ Level of abilities (ID/AF) All levels All levels All levels SIB

Definition Operational (RBQ) n.m. n.m.

Prevalence 70.3% 36% (20/56) 55% (27/49)

Age of onset n.m. n.m. n.m.

Provocative influences n.m. - Thwarting; frustration; anxiety; fear; boredom; demand avoidance Form(s)/topography2 _{OR: Hits with body 4.03; hits against object}

2.69; hits with object 4.71; bites self 2.55; pulls self 4.99; rubs/scratches self 3.04; inserts 3.83

n.m. Finger biting, head banging, scratching, wrist biting, eye poking;

70%> 1 site

Duration n.m. n.m n.m.

Frequency n.m. n.m Occasional (n.o.s.)

Intensity n.m. n.m. n.m.

Severity n.m. Scratches or picks on the skin “Severe” (n.o.s.) SIB related results Behavioral

Physical

SIB more in CdCS, CdLS, fraX, PWS, LS and SMS.

SIB associated with repetitive and impulsive behavior

n.m.

Correlation with phenotype, increased age, low cognition, communication skills, high pain threshold, autistic-like behavior, compulsive behaviors

n.m.

Correlation with increased age, ASS; low cognition; triggers thwarting or frustration (34%), anxiety or fear (18%), boredom (13%), demand avoidance (5%)

Type pub Original Original Original

Study design Cross sectional Cross sectional Cross sectional

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6 CdLS

General

Author / year Eden / 20144 _{Hall / 2008}5 _{Hyman / 2002}6

Aim SIB-aggression Health, sleep, SIB SIB, self-restraint, compulsive behavior Methods Questionnaire Interview, questionnaire Questionnaires

Study population

Entity Various syndromes / CdLS CdLS / matched control group CdLS

Acquisition Support group Support group Support group

Selection criteria CdLS Diagnostic info, age, distance n.m. (88/229, bias?)

Confirmation diagnosis n.m. n.m. Informant-based

Physical exams Questionnaire Health questionnaire, ISQ Hearing and vision questionnaire Results Disturbed vision 33.7%, disturbed hearing

42.6% Eye (36.7:36.4); GI (71.2:31.8); genitalia (28.8:4.5); hernia (25.0:2.3); problems increasing with age

45% hearing +/- vision problems

n 61 54 / 46 88

Age: mean/SD/range 10.10/3.25/? 13.88/8.58/? 12.89/8.02/1-38

Male : Female 27:34 25:29 42:46

Studied features SIB, challenging behavior, repetitive behavior, hyperactivity/impulsivity, mood, social communication, abilities

SIB, challenging behavior, abilities SIB, self-restraint, compulsive behavior, abilities

Assessment (SIB/other behavior/abilities) CBQ, RBQ, TAQ, MIPQ, SCQ, Wessex CB interview, Wessex Own questionnaire (incl. SIB, Wessex, challenging behavior), CB checklist, SR checklist

Level of abilities (ID/AF) n.m. All levels All levels

SIB

Definition n.m. Operational (CB interview) Operational (questionnaire)

Prevalence 63.9% n.m. 63.6% (56/88)

Provocative influences n.m. n.m. n.m.

Form(s)/topography2 _n.m. _n.o.s. _n.o.s.

Duration n.m. n.m. n.m.

Frequency n.m. n.m. n.m.

Intensity n.m. n.m. n.o.s.

Severity n.m. n.m.. n.o.s.

SIB related results Behavioral Physical

SIB associated with low mood, hyperactivity, impulsivity, repetitive use of language, pain-related behavior

n.m.

Correlation with skin problems; no correlation with other health problems or sleep problems

Correlation with age (>12 yrs); correlation SIB and self-restraint; correlation compulsive behaviors with SIB + self-restraint n.m.

Study appraisal

Study design Case-control Case-control Cross sectional

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7 CdLS

General

Author / year Hyman / 20017 _{Johnson / 1976}8 _{Moss / 2005}9

Aim Parents’ perspective Behavioral phenotype Environmental influence Methods Interview, questionnaire Observations Observations Study population

Entity CdLS CdLS CdLS

Acquisition Support group Tertiary (psychology) center

(human interaction laboratory) Support group, referral physicians, head teachers Selection criteria n.m. n.m. High SIB rate, school education, distance

(8/59/144)

Confirmation diagnosis Informant-based n.m. n.m.

Physical exams None None Questionnaire

Results n.a. n.a. Poor hearing 4/8 (50%); poor vision 3/8 (38%)

mild epilepsy 3/8 (38%); poor/non-ambulant 3/8 (38%)

n 86 9 8

Age: mean/SD/range 12.89/7.81/1-38 ?/?/5-25 9.83/?/4.25-14.25

Male : Female n.m. 3:9 5:3

Studied features SIB, challenging behavior Behavior (self-aversive, social, repetitive,

stereotypic behavior, autistic) SIB, adaptive behavior, abilities Assessment (SIB/other behavior/abilities) CB interview (questionnaire), PAQ (partly) Observation (videotaped) CB interview part II, VABS, Wessex Level of abilities (ID/AF) All levels n.m. Severe-profound

SIB

Definition Operational (questionnaire) Operational With reference

Prevalence 62.8% (54/86) 43% (3/7) 100% (8/8; case series)

Form(s)/topography2 _n.o.s. _{Hits self, picks chin, pulls hair} _{Hair pulling (1/8); finger biting (3/8), ear}

poking (1/8); finger picking (3/8); arm picking (1/8); body picking (2); head hitting (3/8); lip biting/chewing (1/8);

1 form (1/8); 2 forms (3/8); 3 forms (3/8); 4 forms (1/8)

Duration n.o.s. n.o.s. 1.46-75.17% time

Frequency n.m. n.o.s. n.m.

Intensity n.o.s. Hits self 0-14.9 sec/min

Picks chin 0-1.9 sec/min Pulls hair 0-2.1 sec/min

n.o.s.

Severity n.o.s. n.m. SIB severity score 14-27

According to parents correlation with ID, stereotypic behavior

n.m.

n.m. n.m.

7/8 (88%) >1 form of SIB associated with particular setting

Study design Cross sectional Case study/series Case study/series

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8 CdLS

General

Author / year Oliver / 200610 _{Oliver / 2009}11 _{Rojahn / 2013}12

Aim Environmental influence Prevalence, phenomenology Validation BPI Methods Direct assessment

(research setting) Questionnaires, observation Questionnaire Study population

Entity CdLS CdLS / matched control group CdLS

Acquisition Support group Support group Support group

Selection criteria None Age >2, distance (54/190, bias?) n.m. Confirmation diagnosis No Indirect report/informant based; 2nd_opinion

geneticist (13/54) n.m. Physical exams None Sensitivity to pain rating; ISQ n.m.

Results n.a. Pain rating (mean) 2.46:2.55;

Total sleep score (mean) 12.01:11.67 n.a.

n 16 54 / 46 180

Age: mean/SD/range 7.61/3.68/? 13.9/9.0/? 16.18/10.7/1.5-61.4

Male : Female 9:7 25:54 76:104

Studied features SIB, challenging behavior,

social interaction, adaptive behavior SIB, challenging behavior, compulsive behavior, ASD, adaptive behavior SIB Assessment (SIB/other behavior/abilities) Observation with coding, CB Interview, VABS ABC, CB Interview, CB checklist, GARS, VABS BPI Level of abilities (ID/AF) Severe-profound All levels All levels SIB

Definition With reference Operational (CB interview) Operational (BPI) Prevalence 88% (14/16) 55.6% (30/54) 85 % (154/180) >1 SIB form

Provocative influences Adult attention n.m. n.m.

Form(s)/topography2 _{Hand-picking (3/16); body-picking (3/16); face}

hitting (3/16); body hitting (2/16) Biting (31/54); body to object (15/54); skin picking (41/54); body poking (11/54); striking (15/54); body (35/54); face (37/54); head (17/54); hand (41/54); mouth (6/54)

Teeth grinding 54.0%; head hitting 44.4%; self-scratching 37.2%;

0-11 topographies/person

Duration n.m. n.o.s. n.m.

Frequency n.m. Occurring more than once Frequency scores (4.3-10)

Intensity n.m. n.o.s. n.m.

Severity n.m. n.o.s. Severity scores (3.7-8.0)

Physical

Influence adult attention; SIB variability across conditions

n.m.

Biting hand in CdLS > control group Stereotyped behavior directed towards hands, head, body, hand posturing; hyperactivity/stereotypic, compulsive behavior predicts SIB

n.m.

Correlation with ID

Study design Case study/series Case-control Cross sectional

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9 CdLS

General

Author / year Sarimski / 199713 _{Sloneem / 2009}14 _{Shear / 1971}15

Type of study1 _Behavioral _Behavioral _Combined

Aim Social-emotional factors, parental stress,

communication Environmental influence Phenotype Methods Questionnaires Interview, observations Case report Study population

Entity CdLS CdLS / matched control group CdLS

Acquisition Support group, tertiary (psychology) center Support group Tertiary (medical / psychiatry) center Selection criteria n.m. CdLS + SIB (27 of 54 invited; bias?) SIB + CdLS

Confirmation diagnosis n.m. Clinical Clinical

Physical exams SSBP n.m. Clinical phenotype, lab, X ray

Results Solid food refusal 14/27; marked feeding problems 4/27; nasogastr tubes 3/27; settling problems 7/27; night walking 8/27; sleep medication 1/27

n.a. Classical phenotype;

uric acid, hypoxanthine, xanthine, purine normal

n 27 27 / 17 2

Age: mean/SD/range 7.10/4.9/1-16 14.44/7.31/? 1-6

Male : Female 12:15 14:13 2:0

Studied features SIB, challenging behavior, communicative

behaviors, social-emotional functioning SIB, challenging behavior, adaptive behavior SIB, cognition Assessment (SIB/other behavior/abilities) SSBP, BPI, PVCS, (PSI) CB interview, VABS;

naturalistic observations Observation, Psyche Catell, Piaget Sensori Motor scale Level of abilities (ID/AF) Moderate-severe All levels Profound

SIB

Definition Operational (BPI) Coding individually n.m.

Prevalence 40.7% (11/27) 50% (27/54) 100% (2/2)

Age of onset n.m. n.m. 3 and 4 y

Form(s)/topography2 _{Self-biting 11/27; self-scratching 11/27; head}

banging/self-pitching 9/27; hair-pulling/rumination 8/27; bruxism 14/27

Picking 19/27, poking 3/27, biting 14/27, striking 5/27, body to object 4/27; body 9/27; face 10/27; head 6/27; hand 19/27; mouth 1/27; sense organ 4/27

Sucking/biting fingers, pulling/scratching chin+ chest, dislocating hips, biting shoulders, knees, lip picking chest / face

Frequency n.o.s. n.m. n.m.

Severity n.o.s. n.m. Excoriation, bleeding skin; hypertrophic

lesions, fissure SIB related results Behavioral

Physical

Correlation with ID (in age>6yr) and communication competence

n.m.

In 7/27 environmental influence on form of SIB; in 6/27 environmental influence on topography of SIB;

associations between environment and SIB not different between CdLS and comparison group

n.m.

Intensive operant behavior training useful

Study design Cross sectional Case-control Case study/series

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10 CdLS

General

Author / year Wulffaert / 200916 _{Menolascino / 1982}17

Type of study1 _Combined _Behavioral

Aim Phenotype, parental stress Behavioral phenotype Methods Questionnaire, interview, medical exam Observation / intervention Study population

Entity CdLS CdLS

Acquisition Support group, tertiary (medical) center Tertiary (psychology) center Selection criteria CdLS confirmed n.m.

Confirmation diagnosis Clinical + molecular n.m. Physical exams Physical severity score n.m. Results Severity 5-14 (M 9.4, SD 2.2);

Classical phenotype 70%; mild phenotype 19%; atypical 11%

n.a.

n 37 1

Age: mean/SD/range 18.1/13.0/1.4-46.2 14

Male : Female 21:16 1:0

Studied features Challenging behavior, adaptive behavior SIB Assessment (SIB/other behavior/abilities) DISCO-10, DBC-P, VABS (NPSI-S) Observation Level of abilities (ID/AF) All levels Severe SIB

Definition Operational (DISCO-10) n.m.

Prevalence 49% (18/37) 100% (case report)

Age of onset n.m. n.m.

Provocative influences n.m. n..m

Form(s)/topography2 _n.m. _{Picking back neck, chin}

Duration n.m. Persistent

Frequency Frequently 8/37 (22%), occasionally 14/37

(38%) n.o.s.

Intensity n.m. n.o.s.

Severity n.m. “Severe” (n.o.s.)

Correlation with functioning persons, ASS Correlation with physical severity score and gene

Marked obstinacy, hyperactivity, non-attending minimal tasks; influence positive behavioral programming

Type pub Original Original

Study design Cross sectional Case study/series

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11 Cri du Chat

General

Author / year Arron / 20111 _{Cornish / 1996}18 _{Ross Collins / 2002}19

Aim Phenomenology Phenotype Prevalence

Methods Questionnaires Questionnaire Questionnaire

Study population

Entity Various known syndromes / CdC CdC CdC

Acquisition Support groups Support group Support group

Selection criteria ID + known syndrome (CdC) CdC CdC

Confirmation diagnosis n.m. Cytogenetic n.m.

Physical exams Questionnaire Questionnaire n.m.

Results Disturbed vision 15.5%, hearing loss 17.2% Eating < normal 3/27; eating > normal 5/27; pica 11/27; abnormal vision 4/27 n.a.

n 58 27 66

Age: mean/SD/range 17.20/12.16/? 8.3/?/4.0-16.0 14.75/?/6-37

Male : Female 21:37 13:14 27:29

hyperactivity/impulsivity, mood, ASD, abilities SIB, other behaviors, cognition SIB, stereotypy, challenging behavior Assessment (SIB/other behavior/abilities) RBQ, TAQ, MIPQ, ASQ, Wessex SSBPQ, BPVS BPI

Level of abilities (ID/AF) All levels All levels Moderate-severe SIB

Definition Operational (RBQ) n.m. Operational (BPI)

Prevalence 76.8% 70.3% 92%

Form(s)/topography2 _{OR: Hits with body 3.05; hits against object}

2.98; hits with object 5.75; bites 2.89; pulls 10.90; rubs/scratches 4.51; inserts 2.44

n.m. Self-biting 47.0%; head to body 55.0%; body to body 31.8%; head to object 47.0%; body to object 21.2%; pulling hair 34.8%; scratching 40.9%; pinching 25.8%; fingers in cavities 33.3%; objects in cavities 19.7%; pica 27.3%; teeth grinding 43.9%; extreme drinking 19.7; vomiting/rumination 57.6%; air swallowing 4.5%.

1 topo 6%; ≥2 topo 86%; >10 topo 8%

Frequency n.m. n.m. Extremely variable

Severity n.m. n.m. n.m.

SIB more in CdCS, CdLS, fraX, PWS, LS and SMS.

SIB associated with repetitive and impulsive behavior

n.m.

Correlation between stereotypy and SIB; aggression and SIB

Study design Cross sectional Cross sectional Cross sectional

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12 Cri du Chat

General

Author / year VanBuggenhout / 200020

Type of study1 _Behavioral

Aim Changing phenotype with age

Methods Observation

Study population

Entity CdC

Acquisition n.m.

Selection criteria n.m. Confirmation diagnosis Cytogenetic

Physical exams Physical exam, molecular re-analysis Results Face signs less obvious with time.

Del(5)(p14.1) 1/7 Del(5)(p13.3) 5/7 Del(5)(p15.31) 1/7 n 7 Age: mean/SD/range 47, 45, 44, 43, 25, 16, 18 ?/?/16-47 Male : Female 4:3 Behavior / Cognition

Studied features SIB, psychomotor abilities Assessment (SIB/other behavior/abilities) Observation, Termann-Merrill Level of abilities (ID/AF) Mild 1/7, severe-profound 6/7 SIB

Definition n.m.

Prevalence 71%

Age of onset n.m.

Provocative influences Frustration (1/7)

Form(s)/topography2 _{Nail/hand biting, head banging, scratching}

Duration n.m.

Frequency n.m.

Intensity n.m.

Severity n.m.

SIB unchanged over time n.m.

Study appraisal

Type pub Original

Study design Case study/series

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13 Down

General

Author / year Ball / 197521 _{Bhattacharyya / 2010}22 _{Buono / 2010}23

Type of study1 _Behavioral _Combined _Behavioral

Aim External influences Correlation SIB-Phenotype SIB phenomenology

Methods Observation Observation Questionnaire

Study population

Entity Various etiologies / DS Various etiologies/ DS Various etiologies / DS Acquisition Tertiary (behavioral) center Tertiary (medical) center From 1040 ID persons n.o.s

Selection criteria SIB n.m. ID

Confirmation diagnosis n.o.s. Molecular n.m.

Physical exams Medical report/history Physical exam n.m. Results Decreased vision, hearing loss, heart

malformation In DS more minor anomalies n.m.

n 3 (case series)/1DS 70 25

Age: mean/SD/range 11 ?/?/3-37 15.3/10.6/?

Male : Female 1:0 n.m. 16:9

Studied features SIB SIB, challenging behavior/psychiatric

disorders SIB

Assessment (SIB/other behavior/abilities) Observation DASH-II SRCA

Level of abilities (ID/AF) Profound n.m. All levels

SIB

Definition n.m. n.m. With reference

Prevalence 100% (case study) n.m. 45.4%

Age of onset n.m. n.m. <7: 72%; 7-12:12%; 13-18: 4%; >18: 12%; not valuable: 0

Form(s)/topography2 _{Heavy blows to the Adam's apple with closed}

fist. n.m. Hitting with hand 28%; object-hitting 12%; skin-picking 8%; self-scratching 0; grinding teeth/self-pinching 4%; object-finger in cavities 12%; self-biting 12%; hair-pulling 4%; nail pulling-eating 24%; teeth grinding 32%; mouth (48%), hands (44%), head (29%), cheeks (12%), ears (8%)

Severity Prominent scars n.m. n.m.

Apparatus giving shocks successfully faded out for extended periods of time and control generalized across settings and people n.m.

n.m.

SIB negatively correlated with head circumference and positively with ear anomalies

Topographies different in various syndromes (mouth, teeth grinding)

n.m.

Study appraisal

Study design Case study/series (intervention) Case-control Cross sectional

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14 Down

General

Author / year Eden / 20144 _{Fisher / 1997}24 _{Fisher / 1998}25

Aim SIB-aggression External influences Environmental influences

Methods Questionnaire Observation Functional analysis / experimental (TENS) Study population

Entity Various syndromes / DS Various etiologies / DS DS

Acquisition Support group Tertiary (behavioral) center Tertiary (behavioral) center

Selection criteria DS ID+SIB DS+SIB

Confirmation diagnosis n.m. n.m. n.m.

Physical exams Questionnaire Medical history n.m.

Results Disturbed vision 44.2%, disturbed hearing

46.5% Cataract n.a.

n 43 1 1 (case report)

Age: mean/SD/range 9.00/3.31/? 20 25

Male : Female 18:25 1:0 1:0

Studied features SIB, challenging behavior, repetitive behavior, hyperactivity/impulsivity, mood, social communication, abilities

SIB SIB

Assessment (SIB/other behavior/abilities) CBQ, RBQ, TAQ, MIPQ, SCQ, Wessex Functional analysis Functional analysis

Level of abilities (ID/AF) n.m. Profound Profound

SIB

Definition n.m. n.m. Operational

Prevalence 11.9% 100% (case study) 100% (case study)

Provocative influences n.m. n.m. Ignore (automatic reinforcement) Form(s)/topography2 _n.m. _{Punching head/face/ear, scratching}

ear/neck/scalp, eye poking Eye poking, head punching, skin pinching, scratching, head banging

Duration n.m. Continuous n.m.

Frequency n.m. Shown but n.m. Ignore 42.2%; social attention 29.9%; demand 23.7%; toy play 17.2%

Electrical nerve stimulation (TENS): 24.7/min>1.5/min

Severity n.m. “Cauliflower ears”, scars, chronic sores

forehead, ears, scalp Tissue damage, contusions, lacerations, “cauliflower ears” SIB related results Behavioral

Physical

SIB associated with low mood, hyperactivity, impulsivity, repetitive use of language, pain-related behavior

n.m.

SIB reacted to restraints and fading (decrease; different topography) n.m.

Decreased by TENS 10min; increased by TENS 20-30 min loss efficacy TENS with time n.m.

Study appraisal

Study design Case-control Case study/series (intervention) Case study/series (intervention)

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15 Down

General

Author / year Hagopian / 200526 _{Luiselli / 1986}27 _{Maatta / 2006}28

Type of study1 _Behavioral _{Behavioral/pharmacological} _Behavioral

Aim Environmental influences Efficacy treatment Mental health, behavior, ID Methods Functional analysis/ experimental Observation Record study

Study population

Entity DS DS DS

Acquisition n.m. Residential center Total DS pop survey

Selection criteria DS+SIB DS + SIB DS

Physical exams n.m. n.m. Medical records

Results n.a. n.a. Recurrent ear infections

n 1 (case report) 2 129

Age: mean/SD/range 16 10 M 29/0-61; F 35/0-67

Male : Female 1:0 1:1 76:53

Studied features SIB SIB, cognition/abilities SIB, other behaviors, mental health, cognition Assessment (SIB/other behavior/abilities) Functional analysis FA/n.m. Record study

Level of abilities (ID/AF) Profound Severe All levels

SIB

Definition Operational n.m. n.m.

Prevalence 100% 100% (case series) 3% (SIB a.o.)

Age of onset n.m. 8 n.m.

Provocative influences Stereotypy (automatic reinforcement) n.m. n.m. Form(s)/topography2 _{Eye poking} _{Face striking, body pinching, biting hands,}

banging head against fixed surfaces, pulling hair/skin.

n.m.

Duration n.m. n.m.

Frequency Stereotypy, eye poking mean 38.0% of intervals.

Blocking eye poking + response blocking: 7.7% of intervals

1-10 times per hour n.m.

Severity Retinal scarring, permanent visual

impairment Contusions, inflammation, sores, dermal irritation. Patches of baldness, excoriations.

n.m. SIB related results Behavioral

Physical

Decrease after blocking eye poking and response blocking

n.m.

Good reaction SIB on behavioral program SIB persisted under medication

n.m. n.m. Study appraisal

Study design Case study/series (intervention) Case study/series (interventions) Case study/series

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16 Down

General

Author / year Mazaleski / 199329 _{McGlynn / 1997}30 _{Moss / 2013}31

Aim External influences Environmental influences ASD Methods Functional analysis / intervention Direct observation Questionnaires Study population

Entity Various etiologies / DS DS DS / ASD

Acquisition Residential center (institution) n.m. Support group

Selection criteria ID + SIB n.a. DS

Confirmation diagnosis n.m. n.m. Cytogenetic

Physical exams n.m. Medical history n.m.

Results n.a. Deaf, blind n.a.

n 1 1 (case report) 17DS, 17DS+ASD, matched 17ASD

Age: mean/SD/range 32 40 DS: 20.5/11.7/5.0-43.0 DS+ASD: 21.1/11.8/4.0-39.0 ASD: 13.7/8.9/4.0-32.0 Male : Female 0:1 1:0 DS 6:11 DS+ASD 8:9 ASD 12:5 Behavior / Cognition

Studied features SIB SIB SIB, challenging behavior, repetitive behavior, hyperactivity/impulsivity, mood, social communication, abilities

Assessment (SIB/other behavior/abilities) Functional analysis Direct observation CBC, RBQ, TAQ, MIPQ-S, SCQ, Wessex

Level of abilities (ID/AF) Profound Profound n.m.

SIB

Definition n.m. n.m. Operational

Prevalence 100 % (case study) 0 DS 5.9%

DS+ASD 37.5% ASD 52.9%

Form(s)/topography2 _{Body/head hitting, head banging} _{Burst of face slapping} _n.m.

Frequency Fig responses / min n.m. n.m.

Severity Large wound forehead n.m. n.m.

SIB: no reaction on DRO only, good reaction on DRO + extinction

n.m.

Decrease if punishing hand raising (=precursor SIB)

n.m.

Frequency SIB: DS+ASD>ASD> DS n.m.

Study appraisal

Study design Case study/series (intervention) Case study/series (intervention) Case-control

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General

Author / year Oliver / 199832 _{O’Reilly / 2003}33 _{Pace / 1986}34

Aim External influences Environmental influences External influences Methods Observations Functional analysis, observations Observation (intervention) Study population

Entity Various etiologies / DS DS Various etiologies / DS

Acquisition n.m. n.m. n.m.

Selection criteria ID+SIB DS+SIB ID+SIB+self-restraint

Physical exams n.m. n.m. Medical history

Results n.a. n.a. Recurrent ear infections

n 1 1 (case report) 1

Age: mean/SD/range 32 27 15

Male : Female 1:0 1:0 1:0

Studied features SIB SIB, adaptive behavior SIB

Assessment (SIB/other behavior/abilities) Observation Functional analysis; VABS, observation Observation

Level of abilities (ID/AF) Severe Profound Profound

SIB

Definition Operational n.m. With reference

Prevalence 100% (case study) 100% 100% (case study)

Age of onset n.m. 3 yr <1 yr

Provocative influences n.m. Short increase during common cold n.m. Form(s)/topography2 _{Slapping face with hand, banging head onto}

hard surfaces. Head hitting Scratching

Duration Fig % duration n.m. n.m.

Frequency n.m. If alone mean 52.7% of intervals; if demands

mean 43%; if play mean 13%. Fig. % 10-sec intervals SIB

Severity Extensive swelling, cuts; bruising forehead,

face Tissue damage, cauliflower ears n.m. SIB related results Behavioral

Physical

SIB reduced during fading of restraints; increase in positive vocalizations n.m.

Increase if alone, decrease if playing or with demands, or stimulated by vibration or sound.

Increase during common cold.

Self-restraint for SIB decreased by differential reinforcement, and stimulus fading or by air splints and subsequent differential reinforcement.

Study design Case study/series (intervention) Case study/series Case study/series (intervention)

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General

Author / year Prasher / 199635 _{Richards / 2012}36 _{Singhal / 2014}37

Type of study1 _Behavioral _Behavioral _{Mix (clinical/behavioral, cytogenetic)}

Aim Behavior in DS and ASD SIB in ID + ASD Genotype-phenotype Methods Observation Questionnaires Retrospective cohort studies Study population

Entity DS (+ ASD) Various etiologies / DS DS (+SIB)

Acquisition Tertiary (behavioral) center Support groups Database

Selection criteria ID + challenging behavior Age >4 yr, complete SCQ scores All admissions and day cases in NSH hospitals England

Confirmation diagnosis Molecular Molecular/cytogenetic n.a. Physical exams Physical examination, ECG,

hematology/biochemistry / thyroid function n.m. n.m

Results No main abnormalities n.a. n.a.

n 1 (case report) 49 26DS + SIB in 23.995 cases

Age: mean/SD/range 17 15.8/12.6/4-62 n.m.

Male : Female 1:0 21:28 n.m.

Studied features SIB, ASD SIB, challenging behavior, repetitive behavior, hyperactivity/impulsivity, mood, social communication, abilities

SIB

Assessment (SIB/other behavior/abilities) Observation CBQ, RBQ, TAQ, MIPQ, SCQ, Wessex Medical records/HES

Level of abilities (ID/AF) Severe n.m. n.m.

SIB

Definition n.m. n.m. n.m.

Prevalence 100% (case study) 18% n.m.

Age of onset 15 n.m. n.m.

Provocative influences No obvious triggering factor n.m. n.m. Form(s)/topography2 _{Gouging at gums, ear banging} _{Hits with body 6.1%; hits against object 8.2%;}

hits with object 0; bites self 6.1%; pulls self 4.1%; rubs/scratches self 10.2%; inserts 10.2% n.m. Duration n.m. n.m. n.m. Frequency n.m. n.m. n.m. Intensity n.m. n.m. n.m. Severity n.m. n.m. n.m.

Physical

Co-existing DS and ASD

n.m.

SIB associated with autistic behavior within DS, higher levels of impulsivity and hyperactivity, negative affect, low levels of ability and speech.

n.m.

SIB infrequent in DS (RR = 0.11) Study appraisal

Study design Case study/series Case-control Cohort

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General

Author / year Sipes / 201138 _{Solnick / 1977}39 _{Zarcone / 1993}40

Aim Behaviors Environmental influences External influences Methods Questionnaire Functional analysis, direct observation Observation / intervention Study population

Entity Various etiologies / DS DS Various etiologies / DS

Acquisition Database Early Intervention n.m. Residential center (institution)

Selection criteria At risk for ID SIB SIB

Physical exams n.m. n.m. n.m.

Results n.a. n.a. n.a.

n 23 1 2

Age: mean/SD/range n.m. 16 39, 32

Male : Female n.m. 1:0 0:2

Studied features Challenging behavior SIB SIB

Assessment (SIB/other behavior/abilities) BISCUIT Functional analysis, observation Observation Level of abilities (ID/AF) n.m. Severe-profound Profound SIB

Definition n.m. Operational Operational

Prevalence n.m. 100% 100% (case series)

Form(s)/topography2 _{Poking him/herself in the eye 4.3%; harming}

self by hitting; pinching 4.3%; kicking objects 0; banging on objects 4.3%

n.m. Hitting face in area of cheek/temples. Head banging against stationary objects, hitting head with hand, fist, knee, foot

Frequency n.m. >100/30min; icrease when timein condition impoverished, decreasewhen time in condition enriched

Fig responses per min

Severity n.m. n.m. Tissue damage, interference with daily

training SIB related results Behavioral

Physical

SIB not significantly correlated with BISCUIT-results

n.m.

When time in environment was “enriched, timout was effectiveas a punisher n.m.

SIB maintained by negative reinforcement; SIB was reduced more by extinction alone than by extinction plus fading; however, initial increase in SIB

Study design Case-control Case study/series Case study/series (intervention)

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20 fraX

General

Author / year Arron / 20111 _{Bailey / 2008}41 _{Eden / 2014}4

Aim Phenomenology Phenotype SIB, aggression

Methods Questionnaires Questionnaires / interview Questionnaire Study population

Entity Various known syndromes / fraX FraX Various syndromes / fraX Acquisition Support groups Support groups, referral physicians Support group Selection criteria ID + known syndrome FraX carrier / full mutation FraX Confirmation diagnosis n.m. Molecular (1768/2964) n.m. Physical exams Questionnaire Questionnaire: seizures Questionnaire Results Disturbed vision 11.1%, hearing loss 2.1% Seizures: 7%

Full mut M/F: 18%/7% Premut M/F: 8%/1%

Disturbed vision 12.5%, disturbed hearing 2.7%

n 191 FraX 2964 + 57 non FraX matched controls 112

Age: mean/SD/range 16.57/8.81/? ?/?/? 10.88/2.58/?

Male : Female 191:0 1845:1117 (2 unknown) 112:0

hyperactivity/impulsivity, mood, ASD, abilities SIB, aggression, hyperactivity, anxiety, mood, ASD SIB, challenging behavior, repetitive behavior, hyperactivity/impulsivity, mood, social communication, abilities

Assessment (SIB/other behavior/abilities) RBQ, TAQ, MIPQ, ASQ, Wessex Questionnaire (4-point scale) CBQ, RBQ, TAQ, MIPQ, SCQ, Wessex

Level of abilities (ID/AF) All levels n.m. n.m.

SIB Definition Operational (RBQ) n.m. n.m. Prevalence 51.3% Overall 10% Full mut M/F: 41%/10% Premut M/F: 8%/3% 54.5% Age of onset n.m. n.m. n.m. Provocative influences n.m. n.m. n.m.

Form(s)/topography2 _{OR: Hits with body 1.85; hits self against}

object 0.87; hits self with object 0.88; bites self 3.39; pulls self 1.87; rubs/scratches 1.09; inserts 0.79 n.m. n.m. Duration n.m. n.m. n.m. Frequency n.m. n.m. n.m. Intensity n.m. n.m. n.m. Severity n.m. n.m. n.m.

Physical

SIB less in AS than in CdCS, CdLS, fraX, PWS, LS and SMS.

SIB associated with repetitive and impulsive behavior.

n.m.

ASD, SIB, and aggression clustered

n.m.

SIB associated with low mood, hyperactivity, impulsivity, repetitive use of language, pain-related behavior.

Study design Cross sectional Cross sectional Case-control

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21 fraX

General

Author / year Hall / 200842 _{Hessl / 2008}43 _{Langthorne / 2012}44

Type of study1 _Behavioral _Physical _Behavioral

Aim Compulsive behavior, SIB, ASD Correlation markers with SIB External influences Methods Questionnaires, interview Genotyping serotonin transporter (5-HTTLPR)

and monoamine oxidase A (MAOA- VNTR) polymorphisms

Functional analysis, interview, questionnaire Study population

Entity FraX FraX Various etiologies / FraX

Acquisition From longitudinal study Tertiary (neurobehavioral) center Support groups, genetic centers Selection criteria FraX + SIB same gender without fraX +

mother carrier FraX SIB, aggression, destruction

Confirmation diagnosis Molecular Molecular Molecular

Physical exams Salivary cortisol measurements n.m. n.m. Results Cortisol levels declining throughout the day

(M=F) n.a. n.a.

n 60 50 34

Age: mean/SD/range M: mean13.21/SD3.16

F: mean13.06/SD3.93 15.6/4.3/8-24 ?/?/5-21

Male : Female 31:29 50:0 31:3

Studied features SIB, compulsive behavior, ASD, cognition SIB, challenging behavior, cognition SIB, challenging behavior, behavioral function, adaptive behavior Assessment (SIB/other behavior/abilities) SIB-C, CBC, ADOS-G, WISC-III, WAIS-III BPI, WISC-III, WAIS-III, WASI ABC-CV, QABF, VABS-SV Level of abilities (ID/AF) Borderline-moderate Borderline-severe Moderate

SIB

Prevalence M:F 58%:17% ( ≥1 form) 79% 63.3%

Form(s)/topography2 _{Hitting self M/F: 1 %/0%}

Biting self M/F: 45%/7% Pulling hair / skin M/F: 3%-3% Rubbing / scratching M:F: 23%:14%

Self-hitting (50%)

Self-biting (30%) n.m.

Frequency n.m. Mean weekly, mode daily n.m.

Severity n.m. In fig log severity*freq index n.m.

No correlation with SIB of age, cognitive level, compulsive behaviors or ASD

No correlation SIB with FMRP, cortisol level n.m.

SIB associated with 5-HTTLPR genotype, not with MAOA-VNTR

Possibly influence SSRI or SNRI medication

SIB related to less attention n.m.

Study appraisal n.m.

Study design Cross sectional Cross sectional Case-control

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22 fraX

General

Author / year Levitas / 198345 _{Machalicek / 2014}46 _{Pegoraro / 2014}47

Aim Phenotype, ASD Challenging behavior/ext influences Phenomenology

Methods Questionnaires, observation Functional analysis Questionnaire, psychiatric assessment Study population

Entity FraX FraX Various etiologies / FraX

Acquisition Tertiary (developmental) center Support group Tertiary (medical, psychiatry) center Selection criteria FraX + ASD Male + full mutation + verbal ID

Confirmation diagnosis Molecular Molecular Molecular

Physical exams History, physical exam n.m. n.m.

Results Macroorchidism 4/6 Macrocephalia 3/6 Sleep problems 4/6

n.a. n.a.

n 6 12 13

Age: mean/SD/range mean 13.0/?/2.3-23.5yr 3.15/?/1.4-4.3 12.0/3.0/?

Male : Female 6:0 12:0 12:1

Studied features SIB, ASD, cognition SIB, challenging behavior, ASD, cognition SIB, cognition Assessment (SIB/other behavior/abilities) ASIEP, CARS, Rimland,

Leiter SB, Yale Developmental RBI, QABF, ADOS, Mullen, PSL-5 Psychiatric assessment, WISC-III Level of abilities (ID/AF) Moderatie-severe n.o.s. Borderline-moderate SIB

Prevalence 83% 50% 23%

Age of onset 1: noticed at age 5 yrs, marked at age 9-10 yrs

2: age 9 n.m. n.m.

Form(s)/topography2 _{Biting body parts 5/6}

Hair pulling 1/6 Hitting head 3/12; head banging 3/12; biting hand 3/12 n.m.

Severity n.m. n.m. n.m.

Physical

n.m.

8/12 negatitvely reinforced challenging behavior in the form of escape from demands and/or escape from social interactions. 9/12 reinforced challenging behavior in the form of obtaining access to highly preferred item

n.m.

Study design Case study/series Case study/series Case study/series (intervention)

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23 fraX

General

Author / year Richards / 201236 _{Symons / 2003}48 _{Symons / 2010}49

Aim SIB in ID + ASD SIB, phenomenology SIB

Methods Questionnaires Questionnaires Questionnaires, interview Study population

Entity Various etiologies/fraX FraX FraX

Acquisition Support groups Support groups, referral physicians Support groups, referral physicians Selection criteria Age >4 yr, complete SCQ scores Male + full mutation Full mutation + SIB

Confirmation diagnosis Molecular/cytogenetic Molecular Molecular

Physical exams n.m. n.m. Questionnaire

Results n.a. n.a. Males sleep problems; Females sensitive to

pain, seizures

n 123 55 (response 82%)+ matched pairs (SIB :

non SIB) : (31:20)

489: matched SIB/no SIB (n=296 pairs) Age: mean/SD/range 15.3/8.7/6-47 6,7/?/1.7-12 15.9/10.9/?

Male : Female 123:0 55:0 440:49

Studied features Challenging behavior, repetitive behavior, hyperactivity/impulsivity, mood, social communication, abilities

SIB, adaptive behavior, ASD SIB

Assessment (SIB/other behavior/abilities) CBQ, RBQ, TAQ, MIPQ, SCQ, Wessex SIB questionnaire (CBCL, VABS, CARS) Questionnaires (incl. pain checklist, RBS, SIB) Level of abilities (ID/AF) n.m. Borderline-severe n.m.

SIB

Prevalence 55% 58% (lifetime), 81% (past month); 56% ≥ 1

forms; 88% ≥ 1 locations M/F: 41%/16.7 % (lifetime); M/F: 32%/11.4% (past month)

Age of onset n.m. M2.6/?/0.6-7 M: <1yr 11.5%; 1-3yr 52%; 4-10yr: 31%;>10yr 6%; F: <1yr 8%; 1-3yr 50%, 4-10yr: 32%; >10yr 10%.

Provocative influences n.m. Change routine 87%; difficult commands 65%; to gain adult attention 3% n.m. Form(s)/topography2 _{Hits with body 25.2%; hits self against object}

11.4%; hits self with object 3.3%; bites 48.0%; pulls 14.6%; rubs/scratches self 14.6%; inserts 8.1%

Forms mean 2/?/range 1-6;

biting 72%, hitting head 41%, picking skin/hair 34%; head banging 17%; scratching 19%, fingers in body cavities 6%;

Head 63%, palm 59%, back of hands 50%, arm 41%,leg 18%, torso 15%

Hitting self M/F 39%/52%; biting self M/F 70%/50%; picking skin M/F 26%/42%; scratching M30%, F32%; Head M/F 46%/51%; arm/hand M/F 80%/76%; torso M/F 20%/18%; leg/foot M/F 16%/31% Duration n.m. n.m. n.m.

Frequency n.m. n.m. Daily M/F 39%/31%; weekly M/F 32%/21%,

monthly M/F 10%/19%, less freq M/F 19%/29%

Severity n.m. n.m. Mild M/F 65%/76%, moderate M/F 30%/26%,

severe M/F 5%/2% SIB related results Behavioral

Physical

SIB associated with autistic behavior within FraX, higher levels of impulsivity and hyperactivity, negative affect, low levels of ability and speech.

n.m.

No correlation with age, topographies; correlation with FMRP. Hazard of onset increased from 12–25 months. No linear increase in risk with age past 25 months. n.m.

Correlation SIB with gender, sleep problems, attention problems, food-sensibilities, autism, anxiety.

Medication effective: some 38%, marked 29%; no gender difference

Rewards/ behavior effect 54%; some 44%, marked 19%

Study appraisal

Study design Case-control Case-control Case-control

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24 fraX

General

Author / year Wolff / 201350

Type of study1 _Clinical

Aim MRI signs correlated with SIB

Methods MRI

Study population

Entity FraX / ASD

Acquisition Tertiary (medical) center Selection criteria FraX / ASD + MRI Confirmation diagnosis Molecular

Physical exams MRI caudate nuclei volumetrics

Results See below

n FXS 41/FXA+ASS 16/ASS 30

Age: mean/SD/range 4.6/0.8/3-6; 4.8/0.8/?; 4.7/0.7/?

Male : Female 41:0

Studied features SIB, repetitive behavior, ASD, adaptive abilities/cognition

Assessment (SIB/other behavior/abilities) RBS-R, ADOS-G, ADI-R, MSEL Level of abilities (ID/AF) Borderline-moderate SIB

Definition With reference

Prevalence n.m. Age of onset n.m. Provocative influences n.m. Form(s)/topography2 _n.o.s. Duration n.m. Frequency n.m. Intensity n.m. Severity n.m.

n.m.

SIB in ASD associated with left caudate volume.

SIB (number topographies) in FraX correlated with bilateral caudate nuclei volumes. Study appraisal

Type pub Original

Study design Case-control

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25 LNS

General

Author / year Adler / 199651 _{Anderson / 1994}52 _{Anderson 1978}54_/197753

Type of study1 _Physical _Behavioral _Behavioral

Aim Phenotype SIB phenomenology SIB contingencies

Methods Observation, lab Questionnaires, photos, video Observation/procedures Study population

Entity Atypical LNV LNS LNS

Acquisition Tertiary (medical) center n.m. Tertiary (medical) center Selection criteria n.m. LNS + SIB (40 selected out of 60) LNS + SIB + inpatients

Confirmation diagnosis Molecular Metabolic Metabolic

Physical exams Lab, neuro exam Questionnaire n.m.

Results Normal tone, brisk deep tendon reflexes, spasticity, dystonia, ataxia, atrophy lower limb muscles.

Absent HPRT activity, HPRT mutation, spontaneously reverted to normal in part of cells (mosaicism)

(Unspecified) physical problems detected at

1-12m n.a.

n 1 40 5

Age: mean/SD/range 22 13.9/?/2-32 8.80/?/3-13

Male : Female 1:0 40:0 5:0

Studied features SIB SIB SIB

Assessment (SIB/other behavior/abilities) Observation, IQ test (n.o.s.) n.m. Observation/procedures Level of abilities (ID/AF) Borderline n.m. Bordeline-mild SIB

Definition n.m. Items questionnaire Operational/descriptive (baseline and intervention scores)

Prevalence Absent 100% (case series) 100% (case series)

Age of onset n.a. 3.0/1.96/1-10 n.m.

Provocative influences n.a. Stress, removal restraints Removal restraints Form(s)/topography2 _n.a. _{Biting any body part 37/40; biting fingers}

29/40; biting lip 33/40; head banging 30/40; neck snapping 34/40; arm/leg in doorway 35/40; feet under wheelchair 23/40; fingers in spokes 17/40; eye poking 13/40

Biting fingers 5/5; biting lip 5/5; head banging 5/5; neck snapping 5/5

Duration n.a. Days-weeks

No change over time once fully expressed n.m.

Frequency n.a. n.m. n.m.

Intensity n.a. n.m. Finger in mouth/min 1-7/min;

head banging/min=6-7/min

Severity n.a. Severity index 7.6/2.91/1-14

Permanent physical damage 36/40 “Severe” (n.o.s.) SIB related results Behavioral

Physical

n.m.

Mosaic HPRT reversion explanation of absent SIB?

Correlation with age of onset; relation to stress; no association with abilities. General health: no correlation Physical discomfort>increase

Punishment no effect; positive reinforcement of non-SIB and time-outs effective. n.m.

Study appraisal

Study design Case study/series Cross sectional Case study/series (intervention)

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26 LNS

General

Author / year Arhakis / 201055 _{Benke / 1972}56 _{Bergen / 2002}57

Type of study1 _Physical _Physical _Behavioral

Aim Oral device Phenotype and biology SIB contingencies

Methods Open trial Observation and cell studies Observation/procedures Study population

Entity LNS LNV LNS

Acquisition Tertiary (medical) center Tertiary (medical) center Residential center (institution)

Selection criteria n.m. n.m. n.a.

Confirmation diagnosis Metabolic Metabolic n.m.

Physical exams Lab, renal imaging Lab, renal imaging, neuro exam n.m. Results Hyperuricaemia nephrocalcinosis.

Renal size normal Hyperuricaemial nephrocalcinosis; hydronephrosis; brisk deep tendon reflexes, increased tone; mild choreoathetosis hands; Cell studies: normal HPRT activity

n.a.

n 1 1 1

Age: mean/SD/range 14 18 28

Assessment (SIB/other behavior/abilities) Observation, intervention Observation Observation/procedures

Level of abilities (ID/AF) n.m. Borderline n.m.

SIB

Definition n.m. n.m. Operational/descriptive (baseline and

intervention scores) Prevalence 100% (case report) 100% (case report) 100% (case report)

Age of onset n.m. 18 n.m.

Provocative influences n.m. Physical discomfort n.m.

Form(s)/topography2 _{Biting lips, tongue} _{Pulling hair} _{Eye gouging (target symptom)}

Severity Permanent damage lip/tongue Large areas alopecia areata n.m. SIB related results Behavioral

Physical

n.m.

Oral device: effective healing

n.m.

Correlation with physical discomfort

Highest rates of precursory behavior at continuous attention and reinforced incompatible behavior.

Social attention is discriminative SIB stimulus. n.m.

Study appraisal

Study design Case study/series (intervention) Case study/series Case study/series (intervention)

(27)

27 LNS

General

Author / year Bigio / 200758 _{Cif / 2007}59 _{Deon / 2012}60

Type of study1 _Combined _Physical _Physical

Aim Phenomenology / Neuropathology Effect bilat pallidal DBS Effect bilat pallidal DBS Methods Autopsy Observation / DBS surgery Observation / DBS surgery Study population

Entity LNS LNS LNS

Acquisition Tertiary (medical) center Tertiary (medical) center Tertiary (medical) center

Selection criteria n.m. LNS + SIB LNS + SIB

Confirmation diagnosis Molecular Molecular n.m.

Physical exams Autopsy n.m. n.m.

Results Cerebellar multifocal internal granular layer

atrophy with sparing of the Purkinje layer n.a. n.a.

n 2 1 1

Age: mean/SD/range 15.9/?/10.8-21 16 10

Assessment (SIB/other behavior/abilities) Observation BPI-01, observation Observation Level of abilities (ID/AF) Borderline-moderate n.m. n.m. SIB

Prevalence 100% (case series) 100% (case report) 100% (case report)

Age of onset 2: 2nd_year _n.m. _{4 yr}

Form(s)/topography2 _{Biting lips, cheeks; picking ear} _{Tongue, lip and hand biting, eye poking} _{Biting finger, lower lip}

Duration n.m. Continuously n.m.

Severity Damage ear (n.o.s.) Lip amputation Painful injuries, constant bleeding for oral injuries

n.m.

Relation with cerebellar anomalies?

n.m.

DBS: in 1st_{week SIB decreased, neuroleptics}

could be decreased, attaching patient to bed / wheelchair became unneeded. Motor symptoms decreased

When DBS was stopped, SIB with teeth grinding recurred after 6 d, and after 3 weeks SIB was as before. When DBS was restarted, control of SIB was obtained in 3 days.

n.m.

< 3 m after DBS improvement in dystonia, complete SIB remission.

Study appraisal

Study design Case study/series Case study/series (intervention) Case study/series (intervention)

(28)

28 LNS

General

Author / year Evans / 199361 _{Fardi / 2003}62 _{Guidera / 1990}63

Type of study1 _Physical _Physical _Physical

Aim Effect lower lip guard Effect palatal plate Orthopedic manifestations in congenitally insensate patients

Methods Observation Observation/treatment Charts/Xray review (14 yr) Study population

Entity LNS LNS LNS (and insensate patients)

Acquisition Tertiary (medical) center Tertiary (medical) center Tertiary (medical) center Selection criteria LNS + SIB LNS + SIB Insensitivity + orthopedic problems

Confirmation diagnosis Metabolic Metabolic n.m.

Physical exams Dental inspection Dental examination Review med records, X-rays Results Marked caries Malocclusion; deep overbite Hip dislocation, osteomyelitis, auto

amputation, scoliosis, oral mutilation

n 1 1 (case report) 2 LNS/8 (case series)

Age: mean/SD/range 11 10 ?/?/1.5-20

Studied features SIB SIB SIB, orthopedic manifestations

Assessment (SIB/other behavior/abilities) Observation Observation Review

Level of abilities (ID/AF) Normal n.m. n.m.

SIB

Prevalence 100% (case report) Biting lip, fingers, hands n.m.

Form(s)/topography2 _{Cheek biting, hand and head banging} _{Lower lip biting} _n.m.

Frequency Off and on n.m. n.m.

Severity Injuries oral tissues, lip trauma, defect lower

lip Ulcer, scarring, missing tissue of lower lip Auto / oral amputation SIB related results Behavioral

Physical

n.m.

Healing lower lip for 9 months, then dribbling causing inflammation and chin damage necessitating removal of appliance and extracting remaining teeth

Foreign objects put in mouth were bitten involuntarily

Appliance reduced damage lower lip

n.m.

Insensitivity caused orthopedic problems and complications

Study appraisal

Study design Case study/series (intervention) Case study/series (intervention) Case study/series

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29 LNS

General

Author / year Hall / 200164 _{Jeong / 2006}65 _{Kale / 2008}66

Type of study1 _Behavioral _{Physical / pharmacological} _Clinical

Aim SIB phenomenology Effect soft mouth guard plus pharmacologic

therapy Effect teeth extraction Methods Interviews, observations Observation/treatment Observation Study population

Entity LNS LNS LNS

Acquisition Tertiary (psychology) center Tertiary (medical) center Tertiary (medical) center

Selection criteria LNS + < 3 y LNS + SIB LNS + SIB

Confirmation diagnosis Metabolic Molecular Metabolic

Physical exams n.m. Oral examination n.m.

Results n.a. Spontaneous tonic biting trapping lower lip between upper and lower anterior teeth n.a.

n 3 1 (case report) 1 (case report)

Age: mean/SD/range 1.4;1.0;1.4 y 4 6

Studied features SIB, adaptive functioning SIB SIB

Assessment (SIB/other behavior/abilities) VABS Observation Observation Level of abilities (ID/AF) VABS equivalent 6-8 months n.m. n.m. SIB

Definition Operational n.m. n.m.

Prevalence 100% (case series) n.m. 100% (case study)

Age of onset 1,2;1.75;1.25 n.m. 2 yr

Provocative influences Constipation, discomfort Frustration, anxiety, aggression n.m. Form(s)/topography2 _{Self-scratching 3/3; head banging 3/3; biting}

body part 1/3; pinching self 1/3 Lip biting Lip biting, biting/chewing thumb and figures hand, toes

Duration <10% of time n.m. n.m.

Severity Open wounds; otherwise n.m. Significant, repeated soft tissue trauma and

infection of lips Lip lacerations, amputations of all fingers/ toes; wounds, gangrene; part lip missing SIB related results Behavioral

Physical

Influence low social interaction

Co-occurrence constipation, discomfort

SIB and anxieties decreased with Sertraline and risperidone After 15 d SIB was markedly reduced, interaction with mother improved; after 1 m SIB was <1attempt/week; after 4 m SIB disappeared completely.

SIB reduced in 2 w of mouth guard and pharmacotherapy. In 1 m biting lip had stopped At 1-yr the patient was very comfortable, and less agitated

n.m.

Central incisors extraction to prevent SIB and assist healing

Study appraisal

Study design Case study/series Case study/series (interventions) Case study/series (intervention)

(30)

30 LNS

General

Author / year Kesiktas / 20067 _{LaBanc / 1981}68 _{Letts / 1975}69

Type of study1 _Physical _Physical _Physical

Aim Reconstruction calcaneal defect Effect teeth extraction Effect seating devices

Methods Observation Observation Observation

Study population

Entity LNS LNS LNS

Acquisition Tertiary (medical) center Tertiary (medical) center Tertiary (medical) center Selection criteria LNS + SIB LNS + SIB + admission LNS + SIB

Confirmation diagnosis n.m. Metabolic n.m.

Physical exams n.m. n.m. n.m.

Results n.a. n.a. n.a.

n 1 (case report) 1 (case report) 2

Age: mean/SD/range 10 5 14, 11

Assessment (SIB/other behavior/abilities) Observation Observation Observation

Level of abilities (ID/AF) n.m. n.m. n.m.

SIB

Prevalence 100% (case study) 100% (case study) 100% (case series)

Provocative influences n.m. Eruption teeth n.m.

Form(s)/topography2 _{Heel battering} _{Finger, lip chewing} _{Hand biting, head banging, flexing knees up}

and flailing them out

Frequency n.m. Repeated episodes n.m.

Severity Ulcers calcaneal region with osteomyelitis;

lacerations of tongue, lips, and fingers Several facial injuries n.m. SIB related results Behavioral

Physical

n.m.

Successful distal pedunculated sural fasciocutaneous flap

n.m.

Successful extraction mandibular incisors n.m.

Seating device reduced SIB Study appraisal

Study design Case study/series (intervention) Case study/series (intervention) Case study/series

(31)

31 LNS

General

Author / year Maramattom / 200570 _{Mizuno / 1979}71 _{Obi / 1997}72

Type of study1 _Physical _Pjysical _Behavioral

Aim Phenomenology Sleep stage (correlation SIB) Behavioral interventions Methods Observation Observation/polygraphy Various behavior strategies Study population

Entity LNS LNS LNS

Acquisition Clinic Tertiary (medical) center Residential center (institution)

Selection criteria LNS + SIB LNS LNS + SIB + restraints

Confirmation diagnosis Metabolic n.m. n.m.

Physical exams CT head, abdominal ultrasound, nerve

conduction studies EOG, EEG, EMG n.m. Results Normal CT; renal calculi; normal conduction

velocities Disturbed sleep, decreased REM density with low DQ n.a.

n 1 5 LNS/3 controls 1

Age: mean/SD/range 12 ?/?/3.5-13.1 24

Studied features SIB SIB SIB, adaptive behavior, cognition

Assessment (SIB/other behavior/abilities) Observation Observation VABS, SIT

Level of abilities (ID/AF) n.m. n.m. Moderate

SIB

Definition n.m. Without reference Operational

Prevalence 100% (case report) 100% (case series) 100% (case study)

Provocative influences n.m. Upon relief restraints n.m. Form(s)/topography2 _{Chewing lips, tongue, arm biting, rubbing}

nose on floor Chewing lips, arms during sleep Head banging, biting fingers, flipping out wheelchair

Duration n.m. n.m. ? (constant restraint)

Severity Missing parts lips and tongue, eroded nose n.m. n.m. SIB related results Behavioral

Physical

n.m. n.m.

n.m.

SIB in stages 1, 2, and REM in 2 cases; No correlation between body movement and SIB.

Restraint fading combined with skill-shaping procedures decreased restraint time (from 22.75 to 12hrs/24hrs) in 2 y

-Study appraisal

Study design Case study/series Case study/series Case study/series (intervention)

(32)

32 LNS

General

Author / year Roach / 199673 _{Robey / 2003}74 _{Schepis / 1996}75

Type of study1 _Combined _Behavioral _Physical

Aim Phenomenology/Neuropathology/Physiology Phenomenology Phenomenology Methods Nerve / muscle biopsies Questionnaire Examinations Study population

Entity LNS LNS LNS

Acquisition Tertiary (medical) center Matheny Int. LND registry Tertiary (medical) center

Selection criteria LNS + SIB n.m. LNS + SIB

Confirmation diagnosis Metabolic n.m. Molecular

Physical exams Neurophysiology, pathology n.m. Neurological exam, MRI, renal ultrasound Results Neurophysiology normal

Light microscopy normal n.a. Choreoathetoid movements, hypotonia, with bouts of hypertonia and opisthotonus, brisk deep tendon reflexes, renal stones

n 4 64 1 (case report)

Age: mean/SD/range 3, 18, 5, 6 16.7/11.1/1-40 9

Male : Female 4:0 63:1 1:0

Assessment (SIB/other behavior/abilities) Observation, videotaping, fam report Questionnaire Observation

Level of abilities (ID/AF) n.m. n.m. Moderate

SIB

Prevalence 100% (case series) 91% (58/64) (all no SIB <4y) 100% (case study)

Age of onset n.m. 2.5y/2.1y/5m-10y 2.5yr

Form(s)/topography2 _{Biting lips, tongue, hands 4/4} ₁st_{SIB: biting lips/fingers}

Biting lips 20/64; biting fingers 24/64; head banging 27/64; arms in doorways 34/64; rubbing head 15/64; eye poking 14/64; fingers in spokes 10/64

Finger and lip biting

Severity n.m. 31/64 facial/oral damage

16/64 damage to hands

Lip, finger injuries, scarring SIB related results Behavioral

Physical

n.m.

With medication/restraint SIB stopped in 3/4 SIB and resumed in 2/4 when carbamazepine was discontinued

Sensory neuropathy not confirmed

Association of particular SIB forms with one another (i.e. biting lips and biting fingers; using external objects as instruments) n.m.

n.m. n.m.

Study appraisal

Study design Case study/series Cross sectional Case study/series

(33)

33 LNS

General

Author / year Schretlen / 200576 _{Scully / 1981}77 _{Smith / 1994}78

Type of study1 _Behavioral _Physical _Physical

Aim Behavior / emotions Phenomenology Phenomenology / effect dental extraction Methods Questionnaire Observation, examinations Observation

Study population

Entity LNS / LNV**/ HC LNS LNS

Acquisition Patient registry, clinics, physicians, school Residential center Emergency room

Selection criteria n.m. LNS + SIB LNS + SIB

Confirmation diagnosis Molecular, metabolic Metabolic Molecular Physical exams Neuro imaging, neurological exam, somatic

questionnaire Physical exam Oral exam

Results n.m. Choreoathetosis, chronic periodontitis Biting pattern analysis: maxillary incisors can remain

n 22 / 11 / 11 1 (case report) 2 (case report twins)

Age: mean/SD/range 22.9/7.7/12-38 12 7

Male : Female 21:1 1:0 2:0

Studied features SIB, challenging behavior, adaptive behavior SIB SIB Assessment (SIB/other behavior/abilities) CBCL, ABS-RC2 Observation Observation

Level of abilities (ID/AF) n.m. Severe n.o.s.

SIB

Definition Operational (ABS-RC2) n.m. n.m.

Prevalence n.m. 100% (case study) 100% (case study)

Age of onset n.m. n.m. 4yr

Form(s)/topography2 _{Biting self, head banging, slapping self/}

striking self, hair pulling Lip and hand biting Thumb, lip and tongue biting

Severity n.m. Loss of tissue lip and tongue, distal limbs

mutilated, scarred Lip and tongue lacerations SIB related results Behavioral

Physical

Correlation with aggression, anxiety, distractibility, stereotypies, disturbing, interpersonal behaviors

n.m.

n.m. n.m.

n.m.

SIB decreased after mandibular teeth extraction

Study appraisal

Type pub Original Original original

Study design Case-control Case study/series Case study/series