Case summaries
Acronyms are used to identify the source of information provided about their level of cognitive/sensory development (e.g. IBQ, VABS). Descriptive data and scores are presented in Additional file 1: Tables S2, S3, S4, S5, and S6.
Case 1: male, diagnosis of NF1, at 10 months
Significant delays in gross motor skills (M, VABS), for example, he was not able to move from sitting to hands and knees, roll over, or pull up from supine to a sitting position. Fine motor abilities were below average for the age group, as he demonstrated a partial pincer grasp but could not take blocks in/out of a container or bang them together (M). Cognitive skills were within the average range (M). Infant demonstrated object permanence, appropriate use of objects, and understanding inhibitory commands. Expressive language was below average and consisted of voluntary babbling and consonant sounds, with no first words or jabbering with inflection (M); receptive language was adequate, but he had difficulty understanding verbal requests and questions from the examiner (M). Broader communication skills were moderately low (VABS). Social skills were a relative strength and judged at age-expected levels (VABS). Examiners reported moderate levels of eye contact and attentiveness, but relatively low levels of shared affect (SE). He showed altered sensory processing across all domains relative to age-appropriate norms (particularly auditory, vestibular, and oral processing); this mainly reflected more registration of sensory stimuli and a low threshold for noticing sensory changes (ITSP). By parent report of temperament, surgency, negative affect, and effortful control were all within one standard deviation of average values in the low-risk sample (IBQ).
Case 2: male, diagnosis of NF1, at 11 months
Gross motor skills were within the normal range by examiner observation (M), and he had strong fine motor skills (M); he had mastered balance and control of the upper/lower extremities and was gaining upright mobility. However, his overall adaptive motor skills were rated lower than average by parent report (e.g. sitting and crawling behaviours occurred lower relative to the age-matched population norm). Cognitive skills were a relative strength—he achieved object permanence and demonstrated early spatial awareness and visual memory (M). Communication skills were relatively poor, specifically in receptive language; he was able to understand simple verbal input (e.g. response to own name or familiar names/words) but failed to give a toy in response to a request and a gesture or identify an object after hearing it named (M). Expressive language was in the average range, marked by presence of first word, as well as communication of intentions through jargon combined with gestures. By parent report, his everyday communication behaviour was relatively strong, as were his social skills (e.g. responding to parent with vocalisation, engaging in games of ‘peek-a-boo’; VABS). Examiners reported frequency of eye contact, shared affect, and social responsiveness (SE). Temperamentally, his surgency and negative affect were within the normal range (though he showed high activity levels in the lab SE), but he showed relatively lower levels of effortful control than low-risk infants (IBQ). Sensory processing was considered typical for most domains, though he showed probably altered auditory processing and definitely less sensation seeking than other infants (ITSP).
Case 3: male, diagnosis of NF1, at 11 months (*)
Gross motor skills were very low (unable to sit independently), and fine motor skills were below average (M): he was able to grasp and manipulate objects, as well as display a partial pincer grasp, but was not able to use both hands together when playing with an object or turn pages in a book. Parent report suggests his use of motor skills in everyday life was adequate but gross motor skills were poorer than fine motor skills (VABS). He had marked difficulty in controlling motor behaviour, although no atypical motor/sensory behaviours specifically related to ASD were noted (AOSI). Cognitive skills were in the low-average range (M); he showed object permanence and began associating objects with functions but was unable to open/close a book or pay attention to pictures. Expressive language skills were very low; he did not babble or produce consonant sounds during the assessment (M). Receptive language was also below average; he was able to give a toy on request, but only when it was accompanied by a gesture, and was not able to understand simple questions from the experimenter (M). During the AOSI, he showed no social babbling. However, by parent report, his communication skills at home were adequate (VABS) and his social skills were strong (VABS). During the day, the child was rated as moderately socially responsive, with moderate eye contact and shared affect (SE), but he showed clearly atypical eye contact, reciprocal smiling, and social interest when probed (AOSI). Temperament was parent-rated as comparable to other groups for surgency and negative affect, but effortful control was lower than in low-risk controls (> − 1SD) (IBQ); examiners also rated him as moderately negative and quite active (SE). Sensory ratings indicated altered visual processing, and definitely ‘less’ low registration (meaning he was less likely to fail to notice sensory stimuli in the environment).
Case 4: male, diagnosis of NF1, at 12 months
Gross motor skills were very low for his age group (M, VABS). He was unable to pull up on furniture or get into a sitting position from hands and knees (M). Fine motor abilities were age-appropriate—he was able to use both hands to manipulate an object and displayed finer coordination of movement (M). Cognitive scores were a relative strength; he obtained object permanence and early spatial awareness and could associate an object and its function (M). Expressive language was very low—he was unable to voluntarily babble or produce any consonant sounds (M). He also showed below-average receptive language ability and was unable to identify an object or respond to a verbal request (M). By parent report, his communication skills were just in the average range. Daily living and social skills were adequate (VABS); examiners also rated his eye contact, affect, and social responsiveness as frequency (SE). Surgency and effortful control were within one standard deviation of the typical range (IBQ), and examiners rated his temperament as very positive (SE); however, by parent report, he showed elevated negativity relative to low-risk controls (IBQ). Sensory sensitivity was within the typical range for all scores, apart from probably altered sensitivity to vestibular sensations (items include needs support for sitting, enjoying physical play, and resists having head tipped back).
Case 5: female, diagnosis of NF1, at 9 months (*)
Gross motor skills were below average in the lab (M) and low in everyday contexts (VABS). Fine motor skills were below average; she was able to use a partial pincer grip, but not both hands together, or turn pages in a book sequentially (M). During the AOSI, she showed marked difficulty controlling motor behaviour, as well as atypical sensory and motor behaviours (AOSI). Cognitive skills were very delayed, with partial object tracking, no object permanence, and failure to associate objects with functions (M). However, by parent report, her daily living skills were typical (VABS). Communication skills were delayed (VABS); during testing, her receptive language skills were rated as below average, while expressive language was a relative strength and age-appropriate, with voluntary babbling and production of several words (M). Everyday social skills were below average (VABS); however, during the testing day, the child maintained relatively frequent eye contact and shared affect with the experimenter (SE) and showed good social skills on the AOSI. Temperamentally, her surgency (e.g. expression of pleasure) and negativity were within expected levels but effortful control was rated lower than low-risk controls (< − 1SD; IBQ). The child showed pervasive atypicalities in the sensory domain, with atypical auditory, visual, tactile, and oral sensory behaviours; these were likely related to more low registration (reduced attention towards environmental cues; ITSP).
Case 6: female, diagnosis of NF1, at 10 months
Gross motor abilities were at floor level in the lab (M), equivalent to a 3-month-old (M). Child was able to bear weight on forearms and hold her head steady in a supported seated position but was not able to roll over or grasp fingers and pull up from a supine into a sitting position. However, she performed at an ‘above average’ level on fine motor skills (M); adaptive fine motor skills were low but in the average range (VABS), showing evidence of the development of more precise coordination of movement. Visual reception skills were age-appropriate, for example, she achieved object permanence and was able to associate objects with functions (M). Expressive language was within the average range; she produced varied and controlled vocalisations and was able to say one recognisable word (M); receptive language skills were below average (M). Parent ratings also indicated moderately low communication abilities (VABS) but relatively strong social skills. During the testing day, she showed frequent eye contact, moderate shared affect, and social responsiveness. Temperamentally, she was rated during the testing day as showing a highly positive temperament though with low attentiveness (SE), and by parent report, surgency, negativity, and effortful control scores were within the average range of control groups (IBQ). Finally, she showed no overt atypicalities in sensory behaviours across all domains (ITSP).
Case 7: female, diagnosis of NF1, at 10 months (*)
Gross motor skills and adaptive motor behaviours were below average for the age range, but fine motor skills were typical (M, VABS) and she showed no motor atypicalities on the AOSI. She had good cognitive ability, including object permanence, early spatial awareness and visual memory (M). Language skills were poor, with low expressive language; she showed voluntary babbling and production of consonants but was unable to vocalise two-syllable sounds or produce first words as expected for the age group (M). She showed very poor receptive language (the 5-month level); she did not respond to her name or understand simple verbal input. Adaptive communication skills were considered strong by parent report (VABS). Social skills in everyday contexts were also typical by parent report (VABS); during testing, she showed frequent eye contact, moderate shared affect, and social responsiveness but became distressed when without her parents. She showed some evidence of diminished social responsiveness to an unfamiliar examiner when promoted (A). Temperamentally, surgency and effortful control were low (< − 1SD) and negative affect was high (> + 2SD) relative to typical controls, although was rated as relatively active and attentive (SE). Sensory responses were altered for auditory and visual domains, likely because she is more likely to notice less sensory cues from the immediate environment (ITSP).
Case 8: female, diagnosis of NF1, at 10 months (*)
Gross motor functioning was poor; she was unable to pull herself to stand or move from sitting position to hands and knees (M); this was accompanied by atypical motor control and behaviours, such as hand waving (AOSI). She also showed poor fine motor skills and was unable to manipulate objects or demonstrate a pincer grasp (M); adaptive motor function was also rated low by parents (VABS). Cognitive skills were below average (although an area of relative strength), with partial object permanence (M), and poor disengagement (AOSI). Language skills were also significantly delayed in both expressive and receptive domains (M) and in everyday contexts (VABS). She was unable to voluntarily babble or produce consonant sounds and showed absent responses to sound or voice/face of the experimenter (M). Social skills in an everyday context were also delayed (VABS). In the lab, she showed moderate to poor eye contact but poor shared affect and social responsiveness (AOSI; SE). Temperamentally, her levels of surgency were relatively low (> − 1SD), as was her effortful control (IBQ). During the testing day, she showed low attentiveness and activity level (SE). Parent-rated reports indicated atypical sensory behaviours across auditory and visual/vestibular and oral sensory domains, mainly related to higher levels of failing to notice sensory stimuli as well as a higher likelihood to have a low threshold for distress reactions (ITSP).
Case 9: female, diagnosis of NF1, at 11 months
Gross motor function was poor; she could sit independently but was not able to walk with one hand held or stand up independently (M). Fine motor skills were typical, including using both hands together and coordinated movements (M); composite motor skills in an everyday context were low to average (VABS). Cognitive skills were below average—she was able to show object permanence and appropriate use of objects but failed to pay attention to pictures shown by experimenter (M). Expressive language skills were very low, with no voluntary babbling or consonant sounds (M). Receptive language was just below average, including giving a toy in response to a verbal request and understanding actions (i.e. waving goodbye or clapping). Overall adaptive communication was rated as adequate (VABS). Social skills were also rated as adequate (VABS), and during the day, she showed frequent eye contact, shared affect, and generally positive temperament (SE). Temperamentally, she showed low surgency and negative affect (< 1SD) relative to low-risk controls; effortful control was high (> 1SD). In the sensory domain, she showed a broadly typical profile, with altered visual processing, probably less likelihood of failing to notice sensory stimuli and probably more sensation seeking (ITSP).
Case 10: female, diagnosis of NF1, at 11 months (*)
Gross motor abilities were low, though she was able to sit independently and turn to reach a toy placed on the side (M). Fine motor skills were also below average, including a partial pincer grasp and object manipulation; however, she was unable to use both hands together or turn pages in a book (M). Adaptive motor skills at home were in the normal range by parent report (VABS), but she showed atypical motor control and behaviours during interaction with an examiner (AOSI). Her visual reception skills were low-average, though she understood object permanence and simple problem solving (M). Expressive language was below average; she is able to babble voluntarily but could not produce consonant sounds and first words or engage in a gesture/language game such as ‘peek-a-boo’ (M). She was functioning at a very low range on receptive language; she did not respond to own name or understand simple verbal input (M). Adaptive communication skills were moderately low by parent report (VABS). Social skills were within the typical range; in the lab, she showed relatively frequent eye contact, but limited shared affect and social responsiveness and social babbling (SE, AOSI). Temperamentally, she showed relatively high levels of negative affect (> 2SD), low effortful control (< 2SD), and high surgency (> 1SD) (IBQ). Sensory behaviours were within the typical range (ITSP).