Table 2. .
Description of Clinical Features of Probands with ASD and SHANK3 Mutations or CNVs[Note]
| Results for Family and Index Patient |
||||
| Characteristic | MM0109 (ASD1) | NA0039 (ASD2) | 3524 (ASD3) | SK0007 (ASD4) |
| Sex | F | F | M | F |
| Exon | 277-kb deletion; 1.4-Mb gain | 3.2-Mb deletion | 4.36-Mb deletion | Q321R mutation |
| Delay: | ||||
| Speech | Nonverbal; no use of gestures or pointing | Vocabulary of 50 words at age 16 years, but uses mainly nonverbal communication | Nonverbal | Stopped using language at age 2–2.5 years; regained some words at age 3.5 years |
| Development | Global developmental delay; poor self-help skills | Global developmental delay; sat at age 13 mo; walked at age 17 mo | Yes | |
| Social interactions/hyperactivity/aggressive behavior | Score of 29 on ADI social reciprocity; no joint attention; not interested in peers; poor use of eyes and facial expression to interact socially | No eye contact; aversion to physical contact | Profound impairment in social interaction; hyperactivity and attention deficits, treated with methylphenidate and risperidone; aggression toward affected sister; mild self-injurious behavior | No eye contact; very limited use of gestures; social withdrawal; currently one friend with developmental delay; severe inattention and irritability, treated successfully with methylphenidate and atomoxetine; mild self-injurious behaviors (biting and hair pulling) |
| Restricted/repetitive behaviors and interests | Carries an object around all the time; score of 4 on ADI repetitive behaviors, Pica, sensitive to sensory stimuli | Self-stimulatory behaviors, such as rubbing clothes and sucking toys | Yes | Fascination with window blinds; understands complex instructions; limited reciprocal conversation about narrow interests; verbal repetitive behaviors; no motor stereotypes; hair pulling |
| Dysmorphic signs | Small head size; hypertelorism | Obesity; soft facial dysmorphism with low frontal hairline; submucous cleft palate with bifid uvula | No | |
| EEG results and seizures | Generalized slowing | Normal CT scan and EEG; history of febrile seizures | Abnormal EEG, with bilateral epileptiform discharges but no seizures; severe sleep disorder; normal CT scan | |
| Instrument scores | At age 7–8 years on Vineland, Communication SS=30, AE=0–11; Daily Living SS=19, AE=1–9; Social SS=41, AE=0–7 | ADI-R = 23 (cutoff 10); ADOS-1=15 (autism cutoff 12); WISC-IV nonverbal subtests + TONI−2: IQ <50 | ADI Social = 24; Communication = 13; Repetitive = 6; Early Abnormal Development = 5; ADOS scores: Communication = 6; Social = 14; Play = 4; Stereotyped Behaviors and Restricted Interests = 5 | Above cutoff in all domains on ADI; borderline ADOS; <1st percentile on old Leiter |
| Comments | Born at 34 wk; birth weight 2,282 g | Single umbilical artery; hand tremor; joint laxity | Sensory defensiveness toward loud noises; no self-injurious behaviors | Conceived by in vitro fertilization; parents are first cousins |
| Family history | Siblings unaffected; no family history of ASD | Sister has ADHD | One affected sister, family history otherwise negative. The affected sister has only a few words. She is noncompliant, with daily temper tantrums when shifted from a preferred to a nonpreferred activity | No family history of ASD |
Note.— AE = age equivalent; EEG = electroencephalogram; IQ = intelligence quotient; SS = standard score; TONI = test of nonverbal intelligence.