Clinical and behavioural features of SYNGAP1-related intellectual disability: a parent and caregiver description

Family, perinatal, and past medical history

All parents reported being non-consanguineous, with 16 parents reporting no previous cases of ID, ASD, ADHD or epilepsy in the first-degree family. Eleven reported that they had extended members of the family (e.g., cousin, uncle, distant relative) who had displayed some form of ID, ASD, or developmental delay.

In regard to perinatal history, all pregnancies proceeded to full-term with the average gestational age being 39 weeks. None of the parents reported a preterm birth prior to 37 weeks. Of the 27 cases, 23 were vaginal births, with five of these being induced, and another three being ventouse deliveries. The remaining four births were via caesarean section. Only one child was reported to have had a very low birth weight (less than 1.5 kg), with the average birth weight being 3.25 kg (min 1.3 kg; max 4.9 kg). Twenty-four parents reported having no exposure to any known teratogens. Those that did reported exposure to flu, listeria infection and the rubella vaccine.

Parents highlighted a range of different conditions that had been experienced by their child including hayfever (4 individuals), reflux (4), dry skin (2), hip dysplasia (2), pneumonia (2), coughs and colds (2), kyphosis (2), and glue ear (2). There were also a number of conditions that were mentioned just once these included febrile convulsion, asthma, ear infections, focal cortical dysplasia, nystagmus, gastrostomy, mycobacteria abscess, hyperinsulinaemia, early menstruation, precocious puberty, depression, anxiety, chest infections, and food-protein induced enterocolitis syndrome. Five parents reported that their child had no previous medical history of note to report.

Epilepsy

Epileptic seizures were reported in 19 out of 27 of our participants, with the average age of onset being 4 years old. Two parents reported that their child had displayed some seizure-like behaviour (e.g., paroxysmal spasms) but they had not received a diagnosis of epilepsy.

Of those children that had received an epilepsy diagnosis, they experienced a range of different seizure types. The most prevalent were absence, followed by atonic, myoclonic, and tonic seizures, and Lennox-Gastaut syndrome. In order to treat their epileptic seizures they had been prescribed a range of different treatments including Sodium Valproate (10), Clobazam (6), Levetiracetam (5), Lamotrigine (4), Ethosuximide (3), Cannabidiol (CBD) oil (1), and the Ketogenic diet (1). Two families who had received a diagnosis of epilepsy reported that their child was currently unmedicated for their seizures.

Developmental history

Developmental history examined language development along with fine and gross motor skills.

In terms of normal development, it would be expected that fine motor skills, particular grasping ability would be developed between 6 and 12 months of age, whilst for gross motor skills by 19–24 months most toddlers would be able to walk unassisted. For language, first words would be produced by the age of 2. However, almost all parents reported that their SYNGAP1 child had some form of developmental difficulty. Fine motor skills varied amongst respondents with five using a fist grip and fourteen using a pincer grip to pick up objects.

For gross motor skills, 21 parents reported that their child was able to walk. However, 12 parents stated that they were unsteady and would stumble when performing this action, which may be the result of ataxia and gait abnormalities which were present for 17 children. Of the children who could walk, six reported that they were also capable of running. All of our samples were aged over three years of age and so these skills (walking, running, and picking up objects) were expected to be present in a typically developed age equivalent cohort. Other gross motor deficits highlighted included low muscle tone (9), hypermobility (3), and dyspraxia/poor coordination (14).

Language abilities were mixed with twelve children reported as being nonverbal (only used gestures, facial expressions, and eye contact to express themselves), whilst seven had better language skills and so were able to articulate either single or multiple words. Of those that were nonverbal or only able to express single words, nine were still able to demonstrate understanding and were able to express what they wanted either through signing or via communicating physically.

Behavioural phenotypeDiagnoses

In total, 52% had received a diagnosis of ASD whilst 7% reported having received a diagnosis of ADHD. One child had received a diagnosis of both ASD and ADHD.

General description

Parents were separately asked to give a general description of their child’s behaviour and then to outline the three main behaviours that caused them or their child the most difficulty. The behavioural phenotype of SYNGAP1 was found to relate to themes of daily living skills, distress-related behaviours, emotional regulation, difficulties with change, a lack of danger awareness, and sensory differences (Fig. 1).

Fig. 1figure 1

Themes and sub-themes of the behavioural phenotype of SYNGAP1-related ID

Daily living skills

A common theme that emerged was difficulties with daily living skills. These quite often concerned eating, sleeping, toileting and social. Sleep was an issue that was often reported by the parents/carers. These sleep issues concerned not only the bedtime routine which for some would take an extended period, but parents reported also that their children would wake repeatedly during the night: ‘Sleep is a huge problem. Very irregular and needs to stick to extremely strict bedtime routine, which takes about an hour and a half’. Another parent commented ‘Sleep is a problem—isn’t on melatonin or anything and usually okay to fall asleep—but wakes during the night and can be wide awake.’ Quite often sleep patterns of SYNGAP1 children were reported to be irregular: ‘Sleep patterns comes and goes in waves—worse when she was baby and still naps in afternoon’. However, some reported that medication seemed to help to ease these difficulties with sleeping: ‘Sleep is better since being on melatonin but will wake around 3/4am and may go back to sleep or be awake for the rest of the night’.

Despite having no or limited language abilities many of the children were still reported to be receptive and keen to have social interactions with others. For example: ‘Enjoys other children. Follows other children in active activities. Will approach other children’. However, this social interaction could sometimes be selective to certain individuals: ‘Has some social interaction with a couple of children in his class. Will ask for one particular child if they are absent and initiates interaction with them’ and ‘he communicates and plays well with his sister. Doesn’t play with others well due to a lack of understanding’ whilst others commented that their child ‘prefers older children and adults’. However, this interest was not universal with other parents highlighting that their child was shy, uninterested in interactions with others or lacking in social skills. Further, many parents reported that their child had good eye contact and would often use it to get attention.

Toileting and eating were two other daily living skills that parents commented on. Some reported that their child had no response to toileting or they had difficulty in going: ‘No sensory response for toileting’ and ‘knows how to go but sometimes doesn’t’ whilst some highlighted that constipation was a problem. Feeding was another issue mentioned by parents. For example, one commented that their child was ‘not a great eater—will try everything but just doesn’t eat a lot. Also has a very sweet tooth’.

Distress-related behaviours

Behaviours consisting of frustration and aggression were a common theme mentioned by the majority of parents. The behaviours demonstrated by those with SYNGAP1 involved being frustrated and aggressive and parents noted this was often due to them being denied something, unable to get their own way or unable to understand the situation. For example, one parent commented that their child: ‘gets anger meltdowns if he doesn’t get his own way’. Quite often this frustration and aggression would result in violence towards other individuals but also towards themselves as illustrated by some parents comments that included ‘tends to swipe at other children and adults in an aggressive way’ and ‘bites herself when she gets frustrated and can scratch others’. This self-injurious behaviour often consisted of them biting their hands, head-banging, and face-hitting.

Emotional regulation

When the parents were prompted about the general mood of their child, they often expressed that they were happy; however, this could change and vary quite quickly to them being upset and frustrated: ‘Gets very upset if fails at something’ and ‘changes from happy to upset quickly’. Anxiety was also mentioned as a concern by a number of parents.

Difficulties with change

Many of the parents highlighted that they were also prone to issues involving transitions and repetitive behaviours. The repetitive behaviours involved various different stimuli or actions, for example one parent commented that their child had ‘many repetitive behaviours like walking up and down stairs and switching on and off lights’, whilst others highlighted repetitive behaviour to sounds, play and the repeating of phrases. Transitions and changes in routines were also issues for the SYNGAP1 individuals: ‘Doesn’t like change from routine’, ‘doesn’t understand now and next’, ‘has around 5-10 outbursts a day, often related to transitions or having to do something she doesn't want to’ and ‘difficult when there is a change in routine’. One parent reported that if the change in routine was small then their child was able to cope with this, however they had issues when it came to transitions: ‘copes well with small changes if well managed but doesn't like transitions’. Also, one parent reported that their child had shown signs of regression with their interests: ‘Has regressed to toddler TV and gets angry and upset with TV for older children. Obsessed with shopping trolleys and fixated on routine’.

Lack of danger awareness

Some of the parents described their child as lacking an awareness of potential dangers in the world. In particular, one parent commented that their child would try to pull away from the parent when out in the community: ‘Lack of danger awareness and bolting behaviour – will try to pull away and escape when out and about and has escaped from buildings’.

Sensory differences

This theme emerged as parents described difficulties stemming from sensory sensitivities such as ‘bothered by loud noises’ and ‘obsessed with gloves’. Some highlighted that their child had strong sensory responses with comments including ‘requires very high stimulation’ and ‘can get overstimulated easily’. Parents brought these issues up spontaneously when discussing behavior, but sensory differences were also explored in more detail through a specific enquiry (see below).

Sensory profile

Many parents and carers reported that their child seemed to respond either particularly positively or negatively to sensory stimuli. In some cases there were specific sensory sensitivities, whereas in other cases parents and caregivers noted that their child seemed to particularly like or be soothed by particular sensory stimuli. These centered on visual, tactile, proprioceptive, gustatory, and auditory modalities (Fig. 2).

Fig. 2figure 2

Themes and sub-themes of the sensory profile of SYNGAP1-related ID

Tactile

Parents highlighted that many children responded particularly to textures, touch, and messy play. In particular, water was frequently reported to be a texture that the children were fixated with and found to be pleasurable to experience: ‘loves running water and bubbles—used to have to cover the sinks at nursery—has to stay in bath until water is drained and if shower is running can get into a tantrum if try to turn it off’. It was also mentioned that textures could be sensations that the children found quite pleasurable whilst others found them aversive. For example, one parent highlighted that their child liked a range of textures: ‘Loves water/swimming, slime and shaving foam’. However, other parents said that textures were sensations that were not particularly liked: ‘dislikes textures (e.g., sand/paint/wet things/soft/sticky)’, whilst messy play was an activity that was particularly disliked by those with SYNGAP1: ‘doesn’t particularly enjoy messy foods or messy play’ and ‘hates being dirty or anything messy’.

Auditory

Parents often reported that their child had sensitivities to auditory stimuli. This sensitivity was predominantly to loud noises and was particularly aversive to those individuals with SYNGAP1. This was emphasised by comments such as ‘hates tannoys and loud speakers’, ‘doesn’t like fire alarms and sounds of people walking’ and ‘hates loud noises and wears ear defenders’.

Visual

Some parents highlighted that their child had visual sensitivities such as to bright lights, with these being a stimulus that they either liked or showed no particular aversive behaviour towards: ‘ok with lights/visual’ and ‘loves bright lights’.

Gustatory

The parents also highlighted that their child with SYNGAP1 exhibited sensitives to particular foods and the act of eating. It was commented that some children had a desire to excessively chew and grind their teeth whilst others disliked food textures: ‘doesn’t like food textures’ and ‘orally sensitive and has need to chew, bite, and grind teeth’.

Proprioceptive

Another sensory sensitivity that was often commented on by parents/carers concerned the environment and in particular experiences that involved motion. For example, it was often mentioned that the children loved watching objects in motion, or that they enjoyed activities such as being in car or being on a swing which involved the sensation of motion. Comments from parents included: ‘Loves rolling things on floor, dropping things, watching cars and being in cars’ and ‘loves motion and wants to have some sort of movement all the time, loves the trampoline and swing and would stay on them all day’.

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