Behavior Problems and Attention Deficit Hyperactivity Disorder in Children and Adolescents with Neurofibromatosis Type 1
Ornella Piscitelli1, Alice Monda1, Maria C Digilio2, Rossella Capolino2 and Vincenzo Di Ciommo2*
1Child Psychiatry Unit, Department of Neuroscience, Bambino Gesù Children’s Hospita, Italy
2Clinical Genetics, Department of Pediatrics, Bambino Gesù Children’s Hospital, Italy
Submission: June 16, 2017; Published: August 03, 2017
*Corresponding author: Vincenzo Di Ciommo, Bambino Gesù Children’s Hospital, Professiona Developmental, Piazza S. Onofrio 4, Roma 00165, Roma, Italy.
How to cite this article: Ornella P, Alice M, Maria C D, Rossella C, Vincenzo D C. Behavior Problems and Attention Deficit Hyperactivity Disorder in
Children and Adolescents with Neurofibromatosis Type 1. Acad J Ped Neonatol. 2017; 5(2): 555716. DOI:10.19080/AJPN.2017.05.555716
Aim:To estimate the prevalence of Attention Deficit Hyperactivity Disorder (ADHD) and of behavioral disorders in children and adolescents with Neurofibromatosis Type 1 (NF1), evaluating possible associations between them
Methods: Patients with NF1 were consecutively enrolled from the outpatient clinic of a pediatric hospital, with their parents as informants. To assess behavior disorders Child Behavior Check List (CBCL) was administered, and parents inattention disease scale (SDAG) with teachers inattention disease scale (SDAI) were used to identify ADHD according to the criteria of the DSM-IV.
Results: Sixty-eight patients with NFI were investigated (mean age 9 years 6 months). Twenty-nine of them fulfilled the criteria of ADHD, with a prevalence of 42.6%. Thirty-one of the patients disclosed problems of behavior (45.6%), with an higher prevalence of internalizing problems in comparisons of externalizing behaviors. Scores of behavior problems were significantly higher in patients with inattentive or combined ADHD than in patients without. Combined ADHD was associated to externalized behavioral problems while the inattentive type was associated to internalized problems.
Interpretation: Behavioral problems and ADHD are common in children and adolescents with NF1 and a link between ADHD and psychological problems can be suggested, but the origins of this relationship remain to be elucidated.
Neurofibromatosis, type 1 (NF1) is a rare, autosomal dominant genetic disorder. It is associated with a mutation on the long arm of chromosome 17, and has highly variable phenotypic expression. Children and adolescents with NF1 have a high incidence of neuropsychological and learning impairments . In 1988 the Conference of the National Institutes of Health established the diagnostic criteria of Neurofibromatosis 1 that were subsequently reconfirmed in 1997 .
In addition to the somatic manifestations, the features of the syndrome have been recognized as including neuropsychological and cognitive problems. The psychological aspects have only
recently become of interest of clinicians and other professional
figures . In spite of the self-concept of children and adolescents appears to be normal, children with NF1 may disclose behavioral and social problems . A study conducted with the Children Behavior Checklist (CBCL)  showed that children and adolescents with NF1 reported high scores on scales of anxiety / depression and social problems in comparison of their healthy siblings . Other studies show the presence of internalizing problems in 39% of children with NF1 and externalizing in 24%. Children with NF1 have greater difficulty interacting with peers. Parents describe them as being loners, shy or awkward with peers .
Compared with their unaffected siblings, children with NF1
showed higher scores on the total problems, internalization and
other domains (social problems, thought problems, and somatic
complaints) . It has been hypothesized that the presence of
high scores in the scale of externalizing is related to attention
problems . The personality profile of children and adolescents
with NF1 differs markedly from the control group. Compared to
the latter, youngsters with NF1 are perceived by their parents
as equally agreeable, but less conscientious in task situations,
less emotionally stable, less open to new ideas, less physically
active, and more extravert, more irritable, and over-reacting to
frustrations, and more dependent on others .
No relation was detected between individual differences in
the personality profiles of patients with NF1 and the severity
of medical problems, the presence versus absence of cosmetic
disfigurement, the mode of inheritance of the syndrome (familiar
versus new mutation) and the Intelligence Quotient . The
somatic manifestations and aesthetic disfigurement commonly
associated with this syndrome may contribute to psychological
and behavioral problems of children and adolescents with NF1,
and may negatively affect their quality of life .
Moreover, children and adolescents with NF1 show higher
prevalence of Deficit Attention / Hyperactivity Disorder (ADHD)
than in the general population [1,11,12]. Using a questionnaire
completed by the parents some authors were able to identify
ADHD in 33% of patients with NF1 in children . An even
higher percentage of this disorder has been documented by a
study in which about 23 children with NF1, almost 50% had been
diagnosed as “hyperactive” or ADHD, but these subjects were
selected from patients a clinic for learning difficulties . One
third of NF1 population of 36 children qualified for a diagnosis
of ADHD by DSM IV criteria . Similarly, studies reported that
49.5% of their 93 child and adolescent patients had ADHD, as
did 36% of their adult patients . With regard to the behavioral
aspects related to ADHD data obtained from questionnaires given
to parents and teachers suggest that problems with concentration
, attention, hyperactivity  and impulsivity  are more
common in children with NF1 than in comparison subjects.
We hypothesized that children with NF1 could have ADHD
associated with emotional disorders, so the aim of the study
was to estimate the prevalence of both disorders in children
and adolescents with NF1, in order to evaluate the associations
between internalizing and externalizing behavior disorders and
types of ADHD.
A cross-sectional design was adopted. Sixty-eight patients
were recruited consecutively from the outpatient Genetics
Clinic of the Bambino Gesù Children’s Hospital in Rome, Italy.
All were diagnosed with NF1 according to the criteria of the
National Institute of Heaslth . Exclusion criteria included
central nervous system lesion or other medical conditions
affecting test performance (e.g. epilepsy/seizures, brain tumors,
hydrocephalus). Social class was classified in five categories
from the highest (professionals and entrepreneurs) to the lowest
(handworkers – housewives).
Child Behavior Checklist (CBCL) – Achenbach  is a
questionnaire developed to measure, in a standardized format,
emotional and behavioral problems in children until 18 years was
used for children and adolescents. It is completed from a parent
and it includes 113 items describing a wide range of emotional
and behavioral problems, to be answered on a three point scale
from 0 (“not true”) to 2 (“very true” or “very often true”) over the
last six months. Eight sub-scales are scored: anxious/depressed,
depressed, somatic complaints, social problems, thought
problems, attention problems, rule-breaking behavior, aggressive
behavior, other problems Summary scores are obtained for
Internalizing behaviors (sum of scores of first three subscales) and
for Externalizing (sum of scores of the subscales: social problems,
thought problems, attention problems, other problems).
Measures consistent with the diagnostic categories of the
American Psychiatric Association Diagnostic and Statistical
Manual of Mental Disorders (Affective, Anxiety, Somatic,
Attention/Hyperactivity, Oppositional and Conduct problems) are
derived from the scores.
Parents inattention disease scale (SDAG) and Teachers
inattention disease scale (SDAI)  are Italian scales for teachers
and parents, to detect children inattention and hyperactivity
behaviors, based on DSM IV diagnostic criteria. Each scale
is composed by 18 items, and their scores are summed and
transformed in scores on a scale of 0 (no problem) to 3 (worst
condition). The odd items amount is related to in attention,
instead impulsiveness and hyperactivity are related to all squared
The patients and their parents were consecutively enrolled;
they completed the questionnaires through three sessions
lasting one hour each, comprising a clinical history, cognitive,
neuropsychological and emotional-behavioral evaluation, ending
with a final report including diagnosis and therapy.
A sample size of 60 total patients was calculated as necessary
to show a significant difference (p < 0.05) of at least 10 points
on a psychometric scale between two groups of patients (e.g.
affected versus not affected) with a power of 0.9. Continuous data
were firstly checked with Kolmogorov-Smirnov test to assess the
normal distribution; they were summarized as means±sfemales
and in children < 11 years, but none of the differences by sex
and age was Standard Deviations (SD) and categorical data as
frequencies. Inferences for comparisons were performer with
t- test for continuous data and chi-square for categorical ones.
Statistical Package for Social Sciences (SPSS, version 12) was used.
The mean of total scores was higher than normal (56.9±11.2
versus 50.0±10) especially for internalizing behaviors (56.4±10.5)
in comparison of externalizing ones (54.7±10.1). The Attention
problems showed the highest score (60.7±9.0) and the Conduct
problems the lowest (56.4±6.4).
According to the CBCL profile-syndrome scale, about a half
of them (31 patients, the 45.6%) disclosed problems of behavior
(either 11 border-line, the 16.2%, or 20 with definite clinical
disorder), with an higher prevalence of internalizing problems in
comparisons of externalizing behaviors (26, the 38.2% versus 19,
When the patients were evaluated according to the CBCL DSMoriented
scale, there was no significant difference between males
and females by number of patients in the clinical or border-line
range, except for a marginally significant higher prevalence of
Somatic Complaints in females (Table 1); similarly no significant
difference was observed between children (<11 years of age) and
adolescents (> 11 years, data not shown).
Twenty-nine children and adolescents with NF1 were affected
by ADHD (42.6%) (Table 2). ADHD inattentive type showed the
highest prevalence in males and >11 years of age and ADHD
impulsive type the lowest, while ADHD combined seems to be
more frequent in males than in significant except an higher
prevalence of ADHD, inattentive type, in males vs females (26.2 vs
11.5, p = 0.02).
In children, 6-11 years, ADHD combined type is the most
frequent, while among the adolescents the largest prevalence was
that of the inattentive type (37.5%) (Table 2).
Attention Deficit Syndrome - Teachers version- could be
obtained only for 31/68 patients, with an high prevalence of
inattentive deficit (20/31, the 64.5%) and of hyperactive deficit
(12/31, the 38.7%).
When we investigated the behavioral scores in patients with
and without ADHD we found that patients with combined ADHD
disclosed higher scores of behavior disorders because a striking
difference of externalizing problems, as patients with inattentive
type of ADHD, while in these last patients this was due mainly to
internalizing problems (Table 3). A lower difference was shown
in impulsive patients versus unaffected patients; in these patients
externalizing scores were higher but did not attained significance,
possibly for low statistical power (Table 3).
In this study we found an high prevalence of children and
adolescent with NF1 satisfying the DSM IV criteria for ADHD
(42.6%) and an high prevalence of behavioral problems (45.6%).
Attention deficits and behavior problems in children with NF1
have been recognized by several studies. Recent papers [3,9,13]
report similar results in children and adolescents affected by NF1.
Furthermore, previous works have pointed out that attention
problems are a matter of preeminent importance in children
with NF1 [17,18]. Specifically, Hyman and Pride  studies
showed more difficulties in switching and sustained attention in
patients with NF1, while other investigators  found deficit in
selective attention too.
With regard to the social component, some researchers
assume that deficits in perception of others emotional expressions
could cause the difficulties shown by children with NF1. According
to Huijbregts , these emotional problems could be explained
by their general cognitive ability, considering processing speed,
social and cognitive control information processing performances.
Furthermore, conduct problems too could be explained by social
information processing deficits. The general cognitive ability
significantly contributes to social responsiveness, while social
information processing is important for problems that individuals
with NF1 have with their peers.
An high prevalence of behavioral disorders was found in our
series, especially for internalizing problems and, as expected, in
the subscale of attention problems. We found approximately the
same results for total scores described in 46 Swiss patients . In
an American series all the subscales were found higher in patients
with NF1, especially for Social Problems, Attention and Thought
 while no difference of internalizing symptoms was found in 54
patients compared with peers in Texas . In 17 Belgian children
the highest scores of CBCL were found for Attention and Social
Problems . We could demonstrate that the psychological
problems may arise in most patients with ADHD, except in those
with impulsive type and these problems show different patterns,
internalizing or externalizing, depending if ADHD is inattentive,
associated with the first ones, or combined, associated with the
second one, a fact not previously assessed to our knowledge.
There are some limitations of this study, such as the absence of
control group of the same sex and age, or that emotional difficulties
weren’t correlated with neuropsychological and cognitive aspects.
Furthermore, we didn’t analyzed the relationship between the
behavioral difficulties showed by our sample and aesthetic and
physical problems commonly associated with this syndrome,
aspects that could be useful for future investigations to better
understand NF1 impact on patients’ life. Due to the crosssectional
design of our study we cannot firmly define the direction
of the cause-effect relationship we found between behavior and
attention deficit, that is, whether internalizing or externalizing
disorders adversely influence ADHD or vice versa.
Finally, our results cannot be necessarily true in other cultural
environments, even assuming that no potential difference could
be attributed to the language of questionnaires.
In summary, there are two important conclusions that can
been drawn from this study. First, we showed an high prevalence
of behavioral problems and of ADHD in our sample, suggesting
that systematic screenings should be part of the clinical approach
to the all the patients with NF1. Second, we found that different
types of behavior disorders are associated with different types of
ADHD, thus suggesting different approaches to interventions.