Clinical Management of Children and Adolescents with Neurofibromatosis Type 1 Like Phenotypes and Complex Behavioural Manifestations: A Multidisciplinary and Dimensional Approach

Table 1

Clinical profile of NF1 patients with an intellectual deficiency.

	Patient 1	Patient 2	Patient 3	Patient 4
Sex, age	Male, 12 years	Male, 13 years	Male, 15 years	Female, 8 years
Main reasons for referral	Increasing puberty-onset aggressiveness	ASD assessment	Psychiatric assessment in the context of sexual assault	Suspicion of ADHD
	Suspicion of ADHD	Suspicion of ADHD	Outpatient unit	Social problems (foster care)
	Inpatient unit	Outpatient unit		Outpatient unit
NF1 diagnosis	Familial NF1 (including intellectual disability)	Sporadic NF1	Familial NF1	Familial NF1
		Additional genetic research was negative: karyotype, x fragile
NF1 complications	Dystrophic thoracic scoliosis	Sphenoid bone dysplasia	Bilateral optic pathway tumor, remission	Optic pathway tumor, remission
	Sphenoid bone dysplasia	Orbicular-facial plexiform neurofibroma (surgically removed)		Precocious puberty
	Labile renovascular hypertension	UBOs: basal ganglia, cerebellum		Epilepsy
	Intermittent claudication			UBOs: left pallidum, white matter
	Several complicated surgical interventions/hospitalisations
	Absence of pheocromocytoma or precocious puberty
	UBOs: bilateral temporal; right lentiform nucleus; cerebellum/protuberance
			Blindness
Developmental delay (early history)	Vineland (age 4): developmental delays ranging from 7–39 months	Hypoxia at birth	?? (family poorly informative)	Prematurity
	(Repeated gastroenteritis during childhood)	(Repeated gastroenteritis during childhood)		PEP-R (age 3): Average developmental delay 11–13 months
Cognitive assessment	TERMAN–MERRILL	PEP-3: mild intellectual disability	Assessment not available	BRUNET-LEZINE (age 3): Developmental delays ranging from 8–14 months
	Moderate intellectual disability	Divided attention TEA-Ch: −2.6SD
		Unimodal attention TEA-Ch −2.6SD
		Language EXALANG: delays in all domains (oral/written) (average: −1.7SD)
		Flexibility NEPSY-II: −1.4SD
		Working memory NEPSY-II: −1.4SD
ASD assessment	CARS (age 4) = 30.5 (mild autism)	Clinical evaluation: repetitive behaviors and perseverant thoughts	No clinical suspicion	ADOS
	ADI-R: stereotypies = 9 (threshold 3)	Deficits in social cognition/pragmatics: −1.3SD ^EMOTION COMPREHENSION TEST		Communication domain = 6 (threshold 4)
	Communication domain = 14 (threshold 8)			Social interaction = 14 (threshold 7)
	Other: anxiety
Psychiatric diagnosis	Moderate intellectual disability	Mild intellectual disability	Mild intellectual disability	Moderate intellectual disability
	Autism	Autism		Autism
	Dyspraxia	Dyspraxia		Dyspraxia
	NF1 related stress (comorbidities)	ADHD-hyperkinetic type		NF1 related stress (comorbidities)
	No criteria for ADHD			ADHD-hyperkinetic type ^CONNERS; clinical assessment
Medication	Aripiprazole	Methylphenidate	None	Levetiracetam
	Melatonin	Melatonin		Enantone
	Labetalol			Methylphenidate
	Clonidine			Risperidone
				Melatonin
Nonpharmacological treatment	Full time school for disabled adolescents, including remediation to improve attention, speech, motricity	Full time school for autistic adolescents	Full time school for disabled adolescents	Full time school for disabled children, including remediation to improve attention, speech, motricity.
	Regular follow-up	Adapted school activities, including remediation to improve attention	Regular psychiatric follow up	Foster family
	Regular multidisciplinary discussion	Speech remediation in the past
Outcome	Clinical improvement	Stable	Improvement	Improvement (less than expected due to social difficulties)
	Balancing day-to-day life with the ongoing co-morbidities of NF1 is a challenge to him and his family			Balancing day-to-day life with the ongoing co-morbidities of NF1 is a challenge to her

ADHD, attention deficit hyperactivity disorder; ADI-R, autism diagnostic interview-Revised [15]; ADOS, autism diagnostic observation schedule [16]; ASD, autism spectrum disorder; BRUNET-LEZINE, First childhood psychomotor developmental schedule [18]; CARS, The childhood autistic rating scale [19]; CONNERS, Conner’s continuous performance test [20]; EMOTION COMPREHENSION TEST, Test of emotion comprehension [27]; EXALANG, language evaluation for children 8–11 years [21]; NEPSY-II, Neuropsychological test for children [22]; NF1, Neurofibromatosis type 1; PEP, Psychoeducational profile: Revised (PEP-R) and third edition (PEP-3) [23]; TEA-Ch, test of everyday attention for children [24]; TERMAN-MERRILL, Stanford-Binet intelligence scale [25]; UBOs, unidentified bright objects; VINELAND, adaptive behaviour scales [28].