bs_bs_banner

Journal of Intellectual Disability Research doi: 10.1111/j.1365-2788.2012.01648.x

874
volume 57 part 9 pp 874–886 september 2013

Neuropsychological profile in adults with

neurofibromatosis type 1 compared to a control group
M.-J. Descheemaeker,1* E. Plasschaert,2* J.-P. Frijns1,2 & E. Legius1,2
1 Center of Human Genetics, University Hospitals of Leuven, Leuven, Belgium
2 Department of Human Genetics, Catholic University of Leuven, Leuven, Belgium

Abstract functions, except for sustained attention. However,

comparison with the IQ-matched control group
Background Neurofibromatosis type 1 (NF1) is a
showed significantly lower scores on visual-spatial
common inherited autosomal dominant condition,
abilities and memory, on auditory working memory
characterised by multiple café-au-lait macules, axil-
and on tests for cognitive flexibility in NF1 adults.
lary and/or inguinal freckling, iris Lisch nodules and
Nevertheless, as the significant difference in average
tumours of the nervous system such as neurofibro-
estimated IQ score between the NF1 group and the
mas and optic pathway gliomas. At the same time,
selected control group almost reaches the 5% sig-
NF1 is frequently associated with intellectual dis-
nificance level, further analysis is needed to include
abilities across several neuropsychological domains.
IQ as a covariate. Eventually, problems in visual-
Existing neuropsychological data in NF1 adults are
spatial skills and auditory long-term memory
limited and sometimes contradictory. Moreover,
seem to be specific NF1-related deficits, while prob-
most studies use a non-IQ-controlled norm group
lems in attention and executive functioning are par-
for comparison. This study sought to investigate
ticularly related to their general lowered intellectual
specific neuropsychological characteristics in intel-
abilities.
lectual abilities unrelated to the global intellectual
Conclusion Taking into account that primary visual
capacity.
perception problems could be part of a more
Method Twenty NF1 adults and an IQ-, age- and
general central coherence deficit while interpreting
gender-matched control group completed a compre-
auditory memory problems as possibly related
hensive neuropsychological test battery composed of
to deficits in language use and comprehension,
specific cognitive tests investigating visual-spatial
this idea also fits with the observation of several
abilities and memory, auditory memory, selective
problems in social information processing and
and sustained attention and executive functioning.
functioning of NF1 persons.
A short version of the Wechsler Adult Intelligence
Scale – III was also administered to both groups. Keywords adulthood, attention, executive function-
Results Norm comparison showed that both ing, memory, neurofibromatosis type 1, NF1
groups perform poorly on most neuropsychological

Correspondence: Dr Eric Legius, Center of Human Genetics, Introduction

University Hospital of Leuven, Herestraat 49, 3000 Leuven,
Belgium (e-mail: eric.legius@uzleuven.be). Neurofibromatosis type 1 (NF1) is a common inher-
*These authors contributed equally to the work. ited autosomal dominant condition, affecting

© 2012 The Authors. Journal of Intellectual Disability Research © 2012 John Wiley & Sons Ltd, MENCAP & IASSID
 Journal of Intellectual Disability Research
875
M.-J. Descheemaeker et al. • Neuropsychological profile in NF1 adults
approximately one in 3000 newborns (Friedman
1999). NF1 is characterised by multiple café-au-lait
macules (CALM), axillary and/or inguinal freckling,
iris Lisch nodules and tumours of the nervous
system such as neurofibromas and optic pathway
gliomas. The clinical diagnosis can be made based
on the diagnostic criteria, formulated by The
National Institutes of Health (NIH) in 1987
(Gutmann et al. 1997). The responsible gene, NF1,
is located on chromosome 17q and encodes the
protein neurofibromin (Cawthon et al. 1990; Visko-
chil et al. 1990; Wallace et al. 1990). Mutations in
this gene result in hyperactivation of the evolution-
ary conserved RAS-mitogen-activated protein kinase
(MAPK) signalling transduction cascade. A spo-
radic mutation is found in approximately half of the
affected persons.
The clinical manifestations of NF1 adulthood are
extremely variable, involving many of the body
systems and are unpredictable within families. A
decrease in CALM with age is reported, while
numerous benign cutaneous and subcutaneous neu-
rofibromas begin to develop around the time of
puberty and continue to develop throughout life,
particularly during pregnancy in women (Duong
et al. 2011). Approximately one half of NF1 patients
have plexiform neurofibromas, but most are internal
and not suspected clinically. In 10% of the patients
with NF1, malignant peripheral nerve sheath
tumours develop, usually in their twenties or thir-
ties. Approximately 15% of patients with NF1
develop optic pathway gliomas and these tumours
may not become symptomatic until later in child-
hood or even in adulthood. Brain tumours, which
are usually gliomas of the brain stem or cerebellum,
occur much more frequently than expected, espe-
cially in young adults. In some adults, glomus
tumours have also been described (Ferner 2010; Jett
& Friedman 2010).
Neurocognitive studies in NF1 individuals have
focused mainly on children. In NF1 children, the
mean IQ is shifted to the left compared to the
general population and sibling controls and ranges
from the high 80’s to the low 90’s (Eldridge et al.
1989; Hofman et al. 1994; Legius et al. 1994; Dilts
et al. 1996; Ferner et al. 1996; North 2000; Hyman
et al. 2005). Although the frequency of mental dis-
abilities (mean IQ <70) in NF1 is only slightly
higher than in the general population (North et al.
© 2012 The Authors. Journal of Intellectual Disability Research © 2012 John Wiley & Sons Ltd, MENCAP & IASSID
volume 57 part 9 september 2013
1997), learning disabilities occur with a prevalence
estimated between 50% and 75% (Brewer et al.
1997; North et al. 1997; Krab et al. 2008). NF1 is
associated with disabilities across different neu-
ropsychological domains. Several studies investi-
gated specific neuropsychological functions in NF1
children. Particularly, deficits in visual-spatial abili-
ties have been reported as being significantly dis-
turbed (Dilts et al. 1996; Hyman et al. 2005;
Clements-Stephens et al. 2008). Some studies found
deficits in attention (Ferner et al. 1996;
Descheemaeker et al. 2005; Hyman et al. 2005),
memory (Ferner et al. 1996; Descheemaeker et al.
2005), language (Hofman et al. 1994; Billingsley
et al. 2003; Hyman et al. 2005) and executive func-
tions, such as planning and organisation and
abstract concept formation (Descheemaeker et al.
2005; Hyman et al. 2005) in comparison with sib-
lings or with a norm population. However, these
deficits were not apparent in all studies (Hofman
et al. 1994; Dilts et al. 1996; Brewer et al. 1997;
Hyman et al. 2005). In addition, some psychiatric
disorders have been observed in NF1 children. Par-
ticularly, an increased rate of at least 30% of atten-
tion deficit hyperactivity disorder is reported
(Mautner et al. 2002; Barton & North 2004;
Descheemaeker et al. 2005; Hyman et al. 2005,
2006). Children with NF1 were diagnosed as
DAMP children, based on their Deficiency in Atten-
tion, Motor and Perception and the repercussions
on behavioural and academic performances
(Descheemaeker et al. 2005). High scores on ques-
tionnaires exploring depressive symptomatology
were also observed in NF1 children (North et al.
1995; Johnson et al. 1999).
Neuropsychological and behavioural data in NF1
adults are less frequently reported and more contro-
versial. Riccardi & Eichner (1986) reported that IQ
scores improve with age. However, Ferner et al.
(1996) found no IQ difference between children and
adults with NF1, while others found a negative cor-
relation between age and IQ (Legius et al. 1994;
Moore et al. 1996). Zöller et al. (1997) compared the
neuropsychological profile of 30 NF1 adults to 30
controls. They found NF1-related deficits in induc-
tive reasoning, visual-constructive skills, visual and
tactual short-term memory, attention, logical
abstraction, coordination and mental flexibility
while, unlike children with NF1, basic motor speed
 Journal of Intellectual Disability Research
876
M.-J. Descheemaeker et al. • Neuropsychological profile in NF1 adults
and vocabulary were not affected. No IQ data were
available in this study. Ferner et al. (1996) studied
103 persons with NF1 and 105 controls, aged
between 6 and 75 years old, matched for age, sex
and socio-economic status. In this study, the degree
of intellectual impairment was mild and NF1
patients had significantly poorer reading skills,
impaired short-term memory, impaired attention
and were slow to develop and adapt strategies for
complex and unfamiliar tasks. However, in the
results a clear distinction between the performances
in children and adults was not always made. Pavol
et al. (2006) administered a battery of neuropsycho-
logical tests to 20 adult NF1 patients and 25 con-
trols. They found that two tests for visual-spatial
skills (developmental test of visual motor integra-
tion and judgement of line orientation) and one
language test (Peabody picture vocabulary
test – revised) were the best predictors for group
membership. They suggested that patients with NF1
tend to have sparing of basic cognitive functions,
but have greater impairment in tests that use
multiple cognitive skills. Using a comprehensive
psychometric test battery, Uttner et al. (2003) com-
pared 20 NF1 adults to 20 age- and gender-
matched control subjects and the NF1 group
showed slightly lowered test scores but no specific
intellectual impairment. On a computerised test of
selective attention, the NF1 group had significantly
slower reaction times. Also, three out of four
memory tests and a test of visual-constructive
abilities showed poorer test results in the NF1
patients. Executive functions were not affected. The
findings supported the idea of a continuum between
childhood and adulthood in NF1 (Uttner et al.
2003).
As neuropsychological data in NF1 adults are
rather limited, sometimes contradictory and fre-
quently based on a non-IQ-controlled norm group
comparison, this study sought to screen for possible
neuropsychological deficits in NF1 adults correcting
for their intellectual capacity (IQ). Based on previ-
ous literature, we expected to observe a specific
neuropsychological profile in NF1 adults with spe-
cific disabilities in visual-spatial skills, memory,
attention and executive functioning. In the present
study 20 NF1 adults (10 female and 10 male) and
the control group of 20 spouses were examined by
using an extensive neuropsychological test battery.
© 2012 The Authors. Journal of Intellectual Disability Research © 2012 John Wiley & Sons Ltd, MENCAP & IASSID
volume 57 part 9 september 2013
Materials and methods
Participants
Participants were recruited from the multidiscipli-
nary paediatric NF1 outpatient clinic of the Univer-
sity Hospital of Leuven. During a period of 6
months, parents of 26 children (<18 years) with
familial NF1 were invited to participate in the
study. The diagnosis in these families was based on
NIH criteria. All children visiting the NF1 outpa-
tient clinic were referred by their primary care phy-
sician or paediatrician with a suspicion of NF1
based on the presence of multiple café-au-lait spots.
Further complications are not necessarily present at
the time of referral. Twenty couples (NF1 group:
n = 20; spouses control group: n = 20) consented to
participate (acceptance rate = 78%). Approval by
the Hospital Ethical Committee was obtained.
All adult participants are Dutch-speaking and
living in the region of Flanders, Belgium (number
of inhabitants: 5 000 000). The Leuven NF1 outpa-
tient clinic is one of four such outpatient clinics in
the region of Flanders. The mean age of the NF1
probands (n = 20) was 41.4 years compared to 41.8
years in the control group of spouses (n = 20;
P = 0.889). There was an equal gender distribution
(10 male and 10 female) and an equal educational
level in the control group compared to the NF1
group (P = 0.397). No significant differences
between sexes were found. One female out of these
20 NF1 patients (5%) suffered from epilepsy and in
another male NF1 patient (5%) a prerolandic brain
tumour in the right hemisphere was observed. No
consequences of these symptoms on neuropsycho-
logical results were noted. Furthermore, NF1
patients were taking no stimulating medication
during the period of testing.
Methods
All persons completed a comprehensive neuropsy-
chological test battery composed of specific cogni-
tive tests investigating visual-spatial abilities,
memory, attention and executive functioning
(Table 1). For some neuropsychological tests, trans-
lated versions in Dutch and Flemish normative data
were used (see Table 1; Miatton et al. 2004). A short
version of the Wechsler Adult Intelligence Scale –
III Nederlandstalige Bewerking (WAIS-III NL),
 Journal of Intellectual Disability Research volume 57 part 9 september 2013
877
M.-J. Descheemaeker et al. • Neuropsychological profile in NF1 adults

Table 1 Overview of intelligence and neuropsychological tests

Intelligence Short form of the WAIS-III NL (Wechsler 2000)

Block Design
Information
Digit Symbol-Coding
Vocabulary

Neuropsychological

Visual-spatial abilities
Block Design (BD from WAIS-III NL,Wechsler 2000)
Complex Figure of Rey: copy (CF, Miatton et al. 2004)
Digit Symbol-Coding (Co from WAIS-III NL,Wechsler 2000)
Memory
Visual-spatial memory Complex Figure of Rey: recall (CF, Miatton et al. 2004)
Auditory memory Auditory Verbal Learning Test (Dutch version) (AVLT, Miatton et al. 2004)
Digit Span (DS from WAIS-III NL,Wechsler 2000)
Attention
Selective attention Bourdon-Wiersma: average time and omissions (BW, Miatton et al. 2004)
Digit Symbol-Coding (Co from WAIS-III NL,Wechsler 2000)
Stroop Coloured-Word Test: colour factor (Dutch version) (SCWT, Hammes 1978; Miatton et al. 2004)
Trail Making Test – part A (TMT – A, Miatton et al. 2004)
Sustained attention Bourdon-Wiersma: average time variability (BW, Miatton et al. 2004)
Executive functions
Auditory Verbal Learning Test: proactive and retroactive interference (Dutch version)
(AVLT, Miatton et al. 2004)
Controlled Oral Word Association Test (Dutch version) (COWAT, Miatton et al. 2004)
Mazes (from WISC-III NL,Wechsler 2002)
Stroop Coloured-Word Test: interference factor (Dutch version) (SCWT, Hammes 1978;
Miatton et al. 2004)
Tower of London (TOL, Krikorian et al. 1994; Miatton et al. 2004)
Trail Making Test – part B (TMT – B, Miatton et al. 2004)
Wisconsin Card Sorting Test completed categories, non-perseverative and perseverative errors
(WCST, Heaton et al. 1993; Miatton et al. 2004)

WAIS-III NL, Wechsler Adult Intelligence Scale – III NL Nederlandstalige Bewerking; WISC-III NL, Wechsler Intelligence Scale for Chil-
dren – III NL.

containing Block Design, Information, Digit
Symbol-Coding and Vocabulary, was administered
to both groups. This short version consists of the
four WAIS subtests with the highest correlation with
total IQ in the general population (Kaufman et al.
1991; Crawford et al. 1992; Silverstein 1992;
Table 1), resulting in an estimated IQ score. This
score represents the mean of the four selected
subtests.
Statistics
Neurofibromatosis type 1 group and control group
are normally distributed. A sample size of 20 is suf-
ficient to show a difference of one standard devia-
tion with a minimum chance of 80% and on a 5%
significance level, as shown by power analysis.
Statistical analysis was executed using the one-
sample z-test, by comparing z-scores of the NF1
group and the control group with data from norm
groups. Secondly, means of raw scores on all tests
of the NF1 group and the control group were com-
pared using t-test comparison and a univariate
analysis of variance (F-test), the latter with IQ as a
covariate. For all statistical tests a significance level
of P = 0.05 was used. Additionally, false discovery
rate (FDR) correction for multiple testing
(Benjamini–Hochberg) was used for 31 independent

© 2012 The Authors. Journal of Intellectual Disability Research © 2012 John Wiley & Sons Ltd, MENCAP & IASSID
 Journal of Intellectual Disability Research volume 57 part 9 september 2013
878
M.-J. Descheemaeker et al. • Neuropsychological profile in NF1 adults

tests except for Auditory Verbal Learning Test
(AVLT) Sum, with a level of significance of P = 0.05
(Thissen et al. 2002).
Results
NF1 group versus control group:
a comparable IQ?
Table 2 shows the estimated intelligence score on
the short version for the WAIS-III of the NF1 group
(89.96, SD 9.23) and of the spouses (95.22, SD
8.60). Both groups perform significantly below
population average (NF1 group: P < 0.001; spouses
group: P < 0.05). Although the difference between
NF1 adults and the control group is not significant,
a marginal significant difference can be observed
(t-test: P = 0.07).
Analysis of one-sample z-tests on subtest scores
shows that NF1 adults as well as the controls
score significantly below population average on all
subtests (Table 2). Significant differences after
FDR correction for multiple testing were observed
for all subtests for both groups in comparison
to the norm. No significant differences were
observed on subtest level between NF1 adults and
the controls, after including IQ as a covariate
(F-test).
Norm group comparison: NF1 adults show
deficits in all neuropsychological domains except
for sustained attention
Table 3 shows the average z-scores of the NF1
group and the control group on several neuropsy-
chological tests next to the one-sample z-test and
P-value for comparison with norm data in both
groups.
In general, NF1 adults perform lower than con-
trols, except for the test parameter measuring selec-
tive attention (Bourdon-Wiersma average time),
where they work faster than the control group. Both
groups perform significantly lower than the norm
group on all tests for visual-spatial abilities (except
for Block Design) and for visual short- and long-term
memory. On tests for auditory short- and long-term
memory, NF1 adults score significantly below
average on all tests, while the control group only
performs weaker on some parameters of the test
(AVLT A1, AVLT Sum). In both groups, no signifi-
cant differences with normative scores are found on
a test for sustained attention. For selective attention,
however, both groups score significantly lower than
norm results on several subtests. They demonstrate
significantly lower scores on Digit Symbol-Coding,
while the NF1 group performs lower on Bourdon-
Wiersma omissions and the control group on
Bourdon-Wiersma average time.

Table 2 One-sample z-test and t-test comparison of NF1 adults and the control group for their mean estimated IQ score (estIQ) and mean
subtest scaled scores on the short form of the WAIS-III

NF1 group U P Control group U P t P

estIQ 89.96 (74–111) -4.862 <0.001* 95.22 (79–110) -2.487 0.02* -1.86 0.07

Subtests NF1 group U P Control group U P F P

Block design 6.5 -8.097 <0.001* 8.3 -2.308 0.03* 1.20 0.28
Digit symbol-coding 6.25 -6.418 <0.001* 7.05 -4.844 <0.001* 0.03 0.87
Information 7.7 -3.322 <0.01* 9.15 -2.129 0.04* 0.23 0.64
Vocabulary 7.6 -3.335 <0.01* 8.8 -2.349 0.03* 0.13 0.72

* Significant results after false discovery rate correction (P = 0.05).

Significant results are shown in bold.
NF1, neurofibromatosis type 1; WAIS-III, Wechsler Adult Intelligence Scale – III.

© 2012 The Authors. Journal of Intellectual Disability Research © 2012 John Wiley & Sons Ltd, MENCAP & IASSID
 Journal of Intellectual Disability Research volume 57 part 9 september 2013
879
M.-J. Descheemaeker et al. • Neuropsychological profile in NF1 adults

Table 3 Average z-scores of the NF1 group and control group on several neuropsychological tests next to the one-sample z-test

NF1 group One-sample Control group One-sample

Mean z (SD) z-test P Mean z (SD) z-test P

Visual-spatial abilities
Block Design -1.17 (0.64) -8.10 <0.001* -0.57 (1.10) -2.31 0.03
Complex Figure – copy -4.35 (3.37) -5.78 <0.001* -2.25 (2.77) -3.63 <0.001*
Digit Symbol-Coding -1.25 (0.87) -6.42 <0.001* -0.98 (0.91) -4.84 <0.001*
Memory
Visual-spatial
Complex Figure
Short recall (short-term) -1.78 (0.79) -10.14 <0.001* -1.41 (1.40) -4.49 <0.001*
Delayed recall (long-term) -1.59 (0.76) -9.44 <0.001* -1.25 (1.28) -4.38 <0.001*
Auditory
AVLT
A1 (immediate recall) -1.28 (0.99) -5.66 <0.001* -1.00 (0.77) -5.70 <0.001*
A2 (learning curve) -0.96 (0.96) -4.35 <0.001* -0.36 (0.78) -2.00 0.06
A3 (learning curve) -0.72(1.12) -2.81 0.01* -0.47 (1.24) -1.66 0.10
A4 (learning curve) -1.03 (1.47) -3.04 <0.01* -0.19 (1.00) -0.83 0.28
A5 (learning curve) -0.97 (1.62) -2.60 0.01* -0.38 (1.18) -1.41 0.15
Sum (short-term memory) -1.184 (1.256) -4.11 <0.001* -0.58 (0.95) -2.66 0.01*
A7 (long-term memory) -0.829 (1.021) -3.54 <0.01* -0.25 (1.18) -0.93 0.26
A8+ (hit rate) -0.793 (1.585) -2.18 0.04* -0.02 (1.24) -0.07 0.40
A8- (false positive) -0.116 (1.214) -0.42 0.37 0.13 (1.20) 0.48 0.36
Digit Span -0.72 (1.05) -3.05 <0.01* -0.27(0.81) -1.47 0.14
Attention
Selective
Bourdon-Wiersma
Omissions -1.38 (2.26) -2.74 0.01* -0.80 (2.36) -1.54 0.13
Average time -0.58 (1.39) -1.88 0.07 -0.79 (1.06) -3.33 <0.01*
Digit Symbol-Coding -1.25 (0.87) -6.42 <0.001* -0.98 (0.91) -4.84 <0.001*
Stroop CF 0.37 (1.04) 1.58 0.11 0.44 (0.79) 2.50 0.01*
TMT – A -0.38 (1.33) -1.29 0.17 0.12 (0.99) 0.68 0.34
Sustained
Bourdon-Wiersma
Average time variability -0.19 (1.20) -0.69 0.32 -0.04 (1.03) -0.16 0.39
Executive functioning
AVLT
B1 (proactive interference) -1.21 (0.76) -6.90 <0.001* -0.70 (0.80) -3.81 <0.001*
A6 (retroactive interference) -0.83 (0.94) -3.86 <0.001* -0.19 (1.13) -0.73 0.31
COWAT
Semantic -0.42 (1.06) -1.78 0.08 -0.36 (0.60) -2.69 0.01*
Phonetic -0.79 (1.26) -2.80 0.01* -0.16 (0.77) -0.90 0.27
Mazes -1.03 (1.26) -3.68 <0.001* -0.67 (0.89) -3.34 <0.01*
Stroop IF 0.17 (0.76) 1.02 0.24 -0.12 (0.73) -0.74 0.30
TMT – B -1.01 (2.23) -2.02 0.05 0.002 (0.95) 0.01 0.40
Tower of London -1.21 (1.30) -4.16 <0.001* -0.91(1.31) -3.08 <0.01*
WCST
Perseverative errors -0.96 (1.30) -3.29 <0.01* -0.56 (1.08) -2.31 0.03
Non-perseverative faults -1.77 (2.35) -3.36 <0.01* -0.83(1.02) -3.51 <0.001*
Categories completed -0.97 (1.48) -2.93 <0.01* -0.18 (1.40) -0.61 0.33

* Significant after false discovery rate correction for multiple testing (P = 0.05).
A negative z-score refers to a weak result; a positive z-score refers to a good result. Significant results are shown in bold.
NF1, neurofibromatosis type 1; AVLT, Auditory Verbal Learning Test; CF, colour factor; TMT – A, Trail Making Test – part A; COWAT, Controlled
Oral Word Association Test; IF, interference factor; TMT – B, Trail Making Test – part B; WCST, Wisconsin Card Sorting Test.

© 2012 The Authors. Journal of Intellectual Disability Research © 2012 John Wiley & Sons Ltd, MENCAP & IASSID
 Journal of Intellectual Disability Research
880
M.-J. Descheemaeker et al. • Neuropsychological profile in NF1 adults
Analysis of different executive functions displays in
both groups several deficits. On the AVLT, proactive
interference (= the interference of list A while asked
for list B) seems to be a problem in both groups,
while retroactive interference (= the interference of
list B while asked for list A) seems to be only a
problem in NF1 adults. Moreover, mental shifting
seems to be an overall problem in NF1 adults, as
they make non-perseverative as well as perseverative
errors (Wisconsin Card Sorting Test). As a conse-
quence, the control group is able to complete more
sequences than the NF1 group, who is performing
below average (Wisconsin Card Sorting Test: cat-
egories completed). On test for planning and organi-
sation (Mazes, Tower of London), both groups
perform significantly below average. On a test for
phonetic word flexibility (Controlled Oral Word Asso-
ciation Test), NF1 adults perform significantly
below average, while on a test for semantic word
flexibility (Controlled Oral Word Association Test),
the NF1 group has a lower average score but norm
group comparison is not significant. After FDR cor-
rection, NF1 adults perform significantly worse on
23/31 (P = 0.05) test variables in comparison to the
norm group, while the controls perform significantly
worse on only 12/31 (P = 0.05) of the tests (chi
square; P = 0.005).
Comparison between groups
Table 4 shows the average raw scores of the NF1
group and control group on several neuropsycho-
logical tests next to t-values (non-IQ-controlled)
and F-values (IQ-controlled), with their
corresponding P-value.
Between-group comparison shows NF1-related
neuropsychological deficits in visual-spatial abilities and
memory, auditory memory and shifting abilities
Significant mean differences between the NF1
group and controls are found on tests for visual-
spatial abilities (Complex Figure P = 0.01, Block
Design P = 0.04), on tests for visual-spatial short-
and long-term memory (Complex Figure P = 0.04,
P = 0.03) and on some tests of auditory short- and
long-term memory (AVLT P = 0.03, P = 0.02,
P = 0.02, P = 0.03 and P = 0.04). Test results of sus-
tained and selective attention did not significantly
© 2012 The Authors. Journal of Intellectual Disability Research © 2012 John Wiley & Sons Ltd, MENCAP & IASSID
volume 57 part 9 september 2013
differ between the NF1 adults and controls. Con-
cerning executive functioning, no significant differ-
ences were found between the NF1 and control
groups, except on a test for shifting between two cat-
egories of stimuli (Trail Making Test – part B),
where NF1 adults are performing significantly
weaker than the controls (P = 0.04). Performance
on two AVLT trials, where shifting between two lists
of words is needed, is also impaired in the NF1
group compared to the control group (P = 0.02,
P = 0.03).
IQ-controlled between-group comparison shows
NF1-related neuropsychological deficits in visual-spatial
abilities and auditory memory
Significant mean differences between the NF1
group and the control group are found on tests for
visual-spatial abilities (Complex Figure copy
P = 0.05) and on some tests for auditory short- and
long-term memory (AVLT A2 P < 0.05, A7 P = 0.05).
Furthermore, performance where shifting between a
new list of words and a previously learned list of
words is needed is impaired in the NF1 group com-
pared to the control group (P < 0.05). No signifi-
cant differences were found on test for selective and
sustained attention and on test for visual-spatial
memory. Nevertheless, no significant differences in
average raw score between the NF1 group and the
controls remain after FDR correction for multiple
testing. However, it is quite unlikely that multiple
test effects are responsible for all 12 significant dif-
ferences before correction of multiple testing.
Discussion
In the present study we investigated performance on
specific neuropsychological tests in 20 NF1 adults
and their spouses as a control group. Results reveal
a mean estimated IQ score of 89.96 in the selected
group of NF1 adults and this is comparable with
the IQ scores reported in children with NF1
(Eldridge et al. 1989; Hofman et al. 1994; Legius
et al. 1994; Dilts et al. 1996; Ferner et al. 1996;
North 2000; Hyman et al. 2005). As intelligence is
one of the factors on which the spouses’ choice is
based (Mascie-Taylor & Vandenberg 1988; Mascie-
Taylor 1989; Thienpont & Verleye 2004), it is not
surprising that the estimated IQ score of the control
 Journal of Intellectual Disability Research volume 57 part 9 september 2013
881
M.-J. Descheemaeker et al. • Neuropsychological profile in NF1 adults

Table 4 Average raw scores of the NF1 group and control group on several neuropsychological tests next to t-test values and F-test values
(IQ-controlled)

NF1 group Control group

Mean (SD) Mean (SD) t P F P

Visual-spatial abilities
Block Design 6.50 (1.93) 8.30 (3.29) -2.11 0.04 1.20 0.28
Complex Figure – copy 28.35 (3.70) 31.33 (3.07) -2.77 0.01 4.04 0.05
Digit Symbol-Coding 6.25 (2.61) 7.05 (2.72) -0.95 0.35 0.03 0.87
Memory
Visual-spatial
Complex Figure
Short recall (short-term) 12.53 (4.98) 16.40 (6.25) -2.17 0.04 2.35 0.13
Delayed recall (long-term) 12.58 (3.92) 16.13 (5.93) -2.23 0.03 2.23 0.14
Auditory
AVLT
A1 (immediate recall) 5.05 (1.67) 5.70 (1.63) -1.25 0.22 1.25 0.27
A2 (learning curve) 7.30 (2.13) 8.95 (2.16) -2.43 0.02 5.42 0.03
A3 (learning curve) 8.95 (2.44) 10.30 (2.43) -1.75 0.09 2.27 0.14
A4 (learning curve) 9.70 (3.03) 11.75 (2.38) -2.38 0.02 3.39 0.07
A5 (learning curve) 10.35 (3.44) 11.95 (2.48) -1.69 0.10 1.74 0.20
Sum (short-term memory) 41.35 (10.53) 48.50 (9.43) -2.26 0.03 3.62 0.07
A7 (long-term memory) 7.90 (2.97) 10.15 (3.30) -2.26 0.03 4.17 0.05
A8+ (hit rate) 12.45 (2.27) 13.70 (1.35) -2.12 0.04 3.63 0.07
A8- (false positive) 2.15 (2.85) 1.40 (2.94) -0.82 0.42 0.66 0.42
Digit Span 7.85 (3.15) 9.20 (2.44) -1.52 0.14 0.61 0.44
Attention
Selective
Bourdon-Wiersma
Omissions 20.75 (11.67) 14.15 (11.03) -1.84 0.07 1.59 0.22
Average time 14.57 (3.40) 15.04 (2.60) 0.49 0.63 1.24 0.27
Digit Symbol-Coding 6.25 (2.61) 7.05 (2.72) -0.95 0.35 0.03 0.87
Stroop CF -3.06 (10.30) -3.82 (7.87) 0.26 0.80 0.02 0.88
TMT – A 39.90 (14.58) 33.10 (6.98) -1.88 0.07 2.44 0.13
Sustained
Bourdon-Wiersma
Average time variability 1.44 (0.72) 1.32 (0.50) -0.64 0.53 0.30 0.59
Executive functioning
AVLT
A6 (retroactive interference) 8.05 (3.02) 10.40 (2.87) -2.52 0.02 4.71 0.04
B1 (proactive interference) 4.10 (1.25) 5.15 (1.66) -2.26 0.03 3.56 0.07
COWAT
Semantic 18.63 (5.27) 19.43 (2.86) -0.60 0.55 0.000 0.99
Phonetic 9.60 (4.77) 12.05 (3.34) 1.07 0.31
Mazes 6.90 (3.77) 8.00 (2.68) -1.88 0.07 0.37 0.55
Stroop IF -3.53 (15.98) 2.67(15.39) 1.25 0.22 0.90 0.35
TMT – B 123.65 (88.40) 80.55 (24.72) -2.10 0.04 2.58 0.12
Tower of London 30.65 (2.74) 31.30 (2.75) -0.75 0.46 0.00 0.99
WCST
Perseverative errors 18.25 (11.80) 14.7 (10.21) -1.02 0.32 0.50 0.49
Non-perseverative errors 23.95 (18.61) 15.95 (10.01) -1.69 0.10 1.31 0.26
Categories completed 4.35 (1.81) 5.30 (1.63) -1.74 0.09 2.25 0.14

Significant results are shown in bold.

NF1, neurofibromatosis type 1; AVLT, Auditory Verbal Learning Test; CF, colour factor; TMT – A, Trail Making Test – part A; COWAT, Controlled
Oral Word Association Test; IF, interference factor; TMT – B, Trail Making Test – part B; WCST, Wisconsin Card Sorting Test.

© 2012 The Authors. Journal of Intellectual Disability Research © 2012 John Wiley & Sons Ltd, MENCAP & IASSID
 Journal of Intellectual Disability Research
882
M.-J. Descheemaeker et al. • Neuropsychological profile in NF1 adults
group is situated in the same range with a score of
95.22. Both groups score significantly lower than
population norms and comparison between groups
displays no significant difference. As a consequence,
spouses could be considered as an IQ-matched
control group. However, as this difference nearly
reaches the 5% significance level, further analysis is
needed to include IQ as a covariate.
In general, specific neuropsychological testing
shows that (1) NF1 adults perform weaker than
controls on most tests and (2) both groups score
significantly weaker than population norms, except
for the average time variability of the Bourdon-
Wiersma. A possible explanation for these low per-
formances in both groups could be that most of the
neuropsychological tests are normed using individu-
als with an average IQ of 100 (SD = 15). Although
current research suggests that specific cognitive
functions are related to overall intelligence, certainly
for people with an average or lower IQ, separate
norms in relation to IQ are unfortunately not avail-
able (Diaz-Asper et al. 2004; Sternberg & Pretz
2005).
Several research groups showed significantly
impaired performances on tests for attention in
adults with NF1 (Ferner et al. 1996; Zöller et al.
1997; Uttner et al. 2003; Pavol et al. 2006). Atten-
tion, as a precursor for all higher cognitive func-
tions, is a complex function. Two different kinds of
attention are studied in this survey: selective and
sustained attention. Norm group comparison reveals
a problem on selective attention tests in the NF1
group as well as in the control group. Although they
have a lower average IQ, their performances on
sustained attention (Bourdon-Wiersma) are still
within normal population range. When evaluating
their working method (Bourdon-Wiersma), a dis-
tinction between the two groups can be made based
on their tactical approach; NF1 adults work faster,
but less accurate. Additionally, no statistically sig-
nificant difference in selective attention is noticed
when NF1 individuals are compared to the control
group, with and without IQ as a covariate. Never-
theless, attention deficits are observed in NF1
children (Ferner et al. 1996; North et al. 2002;
Descheemaeker et al. 2005) and moreover an over-
representation of attention deficit hyperactivity dis-
order is observed in this population (Mautner et al.
2002; Barton & North 2004; Descheemaeker et al.
© 2012 The Authors. Journal of Intellectual Disability Research © 2012 John Wiley & Sons Ltd, MENCAP & IASSID
volume 57 part 9 september 2013
2005; Hyman et al. 2005, 2006; Noll et al. 2007).
Nonetheless, further research, preferably prospective
longitudinal studies, has to exclude a maturation
process in attention functions.
Although visual-spatial abilities and visual
short- and long-term memory are impaired in
both groups, the NF1 group performs significantly
lower on a robust test for measuring visual-
constructive skills in comparison with the control
group, even after including IQ as a covariate. This
deficit has been considered as a hallmark for chil-
dren and adults with NF1 (Dilts et al. 1996;
Zöller et al. 1997; Schrimsher et al. 2003; Uttner
et al. 2003; Descheemaeker et al. 2005; Hyman et al.
2005; Pavol et al. 2006; Clements-Stephens et al.
2008). A possible hypothesis could be that visual
perception problems are part of a more general
central coherence deficit, with a heightened focus
on details rather than the whole picture and difficul-
ties in the integration of separate features (Plaisted
et al. 2003; Pellicano et al. 2005). As several research
groups have confirmed motor difficulties in NF1
children, it should be noted that these Complex
Figure of Rey results may comprise a motor
response deficit (Zöller et al. 1997; Feldmann et al.
2003). However, qualitative analysis of drawn
complex figures shows an average motor response
with most of the time a detail-focused strategy. As
these deficits are a hallmark deficit in NF1 children
and adults, it needs to be emphasised that particu-
larly the nature, the severity as well as the strategy
in visual perceptual and visual-constructive skills
have to be taken into account in further cognitive
NF1 research.
Concerning long-term auditory memory, a sig-
nificant difference is observed in NF1 adults com-
pared to the control group, even after controlling for
IQ. With regard to short-term auditory memory,
tested by the AVLT, an immediate memory compo-
nent and a learning component can be distin-
guished. This last component is processed by
working memory (the evolution in memorising
consecutive trials A1–A5). There is no significant
difference between the performances of the NF1
group and the control group concerning immediate
memory of meaningful (A1) and non-meaningful
information (digit span). However, in contrast to
the control group, NF1 persons are presumably less
able to develop a learning curve (A2). As a conse-
 Journal of Intellectual Disability Research
883
M.-J. Descheemaeker et al. • Neuropsychological profile in NF1 adults
quence, this deficit does not favour the long-term
memory storage of meaningful information. In
summary, auditory working memory impairment
seems to be an important characteristic of the cog-
nitive problems in NF1 adults. Immediate auditory
memory recall is not impaired in NF1 adults com-
pared to the control group, but the control group
benefits more from repetition of information and
from the possibility to make sense of given informa-
tion. As neuropsychological tests including auditory
information as a specific sensory test modality are
absent in NF1 research, future research needs to
consider this.
Deficits in executive functioning have been
reported in NF1 individuals (Zöller et al. 1997;
Uttner et al. 2003; Descheemaeker et al. 2005;
Hyman et al. 2005; Pavol et al. 2006; Krab et al.
2008; Rowbotham et al. 2009; Huijbregts et al.
2010b). Executive functioning is a collective term
for several higher-order cognitive functions targeting
goal- and future-oriented planning and regulation
of thoughts and actions. According to norm group
comparison, NF1 adults and controls encounter
severe impairments on several components of
executive functioning. However, after including IQ
as a covariate, NF1 adults score significantly lower
on only one test for shifting (interference testing
AVLT). We define shifting as the ability to switch a
behavioural response according to the context of
the situation. This finding is possibly a consequence
of the earlier mentioned impairment in imprinting
of auditory information. A more general remark is
the broader and highly important link between
executive functioning and intelligence; as there is a
left shift in the IQ of NF1 patients, obviously execu-
tive functioning will be impaired (Arffa 2007). Addi-
tionally, in future research it will be highly
important to understand and explain the difference
between neuropsychological deficits in executive
function and the everyday executive behavioural
difficulties that may originate from them.
Conclusion
In summary, even in a selected group of adaptive
functioning NF1 adults and based on norm group
comparison, a continuum of several neuropsycho-
logical deficits from childhood to adulthood was
© 2012 The Authors. Journal of Intellectual Disability Research © 2012 John Wiley & Sons Ltd, MENCAP & IASSID
volume 57 part 9 september 2013
observed. These deficits include problems in visual-
spatial abilities and memory, auditory memory,
selective attention and several components of execu-
tive functioning. Remarkably, no deficits in sus-
tained attention were observed.
However, as IQ scores are generally lowered in
NF1 patients, we sought to compare NF1 adults
with an IQ-, age- and gender-matched control
group. The resulting deficits deal with severe prob-
lems in visual-spatial abilities and memory, auditory
working memory and as a consequence problems in
auditory long-term memory function. Also, difficul-
ties in executive functioning are observed, while
unexpectedly no immediate recall and attention
deficits were observed anymore.
Nevertheless, as the difference in average esti-
mated IQ score between the NF1 group and the
selected control group almost reaches the 5% sig-
nificance level, further analysis is needed to include
IQ as a covariate. Eventually, problems in visual-
spatial skills and auditory long-term memory
seem to be specific NF1-related deficits. Problems
in visual-spatial skills are a hallmark deficit in NF1
neuropsychological research, while very little is
known about auditory memory functions.
Taking into account that primary visual percep-
tion problems could be part of a more general
central coherence deficit (Plaisted et al. 2003; Pelli-
cano et al. 2005) while interpreting auditory
memory problems as possibly related to deficits in
language use and comprehension, this idea also fits
with the observation of several problems in social
information processing and functioning of NF1
persons (Dilts et al. 1996; Johnson et al. 1999;
Barton & North 2004; Huijbregts & De Sonneville
2010; Huijbregts et al. 2010a; Descheemaeker &
Plasschaert, unpublished data).
Limitations of this study
As all of the studied NF1 persons are married and
have children, this could have caused a selection
bias towards better adaptive functioning NF1
adults. At the same time, these NF1 adults are
the parents of NF1 children visiting the NF1 outpa-
tient clinic. Also, this latter group is not a repre-
sentative patient group, as children that have no
problems or children that were never referred are
not included.
 Journal of Intellectual Disability Research
884
M.-J. Descheemaeker et al. • Neuropsychological profile in NF1 adults
Regarding intelligence testing, a short form of the
WAIS was administered, while recently more rel-
evant and representative short forms are used
(Crawford et al. 2008; Schrimsher et al. 2008).
Although these four subtests have the highest corre-
lation with total IQ in the general population, this
correlation may not be as high and consistent as in
a NF1 population. Furthermore, IQ is generally an
important factor in influencing scores and interpre-
tations of neuropsychological strengths and weak-
nesses, suggesting that in future NF1
neuropsychological studies, it would be relevant to
compare with IQ-controlled groups, next to norm-
based comparison. Besides, the control group in this
study is not representative for the normal popula-
tion, as their IQ was significantly lower. Altogether,
we believe that characteristics of the two groups in
question produce an underestimation of the actual
group differences between NF1 adults and controls.
Secondly, it is assumed that impaired brain proc-
esses which lead to poor performance on a neu-
ropsychological test can reflect poor performance in
situations outside the test context. In other words, it
is assumed that neuropsychological tests have eco-
logical validity. However, the higher mentioned neu-
ropsychological results are often classified as in
normal range, while several problems in daily life
are noticed (e.g. planning, shifting). As a result,
these neurocognitive measurements should be com-
pleted with additional behavioural measurements,
including self-report and significant other informant
report, as self-insight is rather low in NF1 patients
(Zöller & Rembeck 1999; Barton & North 2007).
Thirdly, in our sample of tests, some conclusions on
neuropsychological components are based on the
results of only one test (e.g. sustained attention).
Upcoming research should include several tests to
draw clear conclusions on broader neuropsychologi-
cal concepts. Finally, it would be interesting to use a
longitudinal approach in further research to evalu-
ate a neuropsychological continuum from childhood
to adulthood, and to have a closer look on how
maturation processes in NF1.
Acknowledgements
We thank Liesje Mertens for her participation in the
neuropsychological assessment and Thomy de Ravel
© 2012 The Authors. Journal of Intellectual Disability Research © 2012 John Wiley & Sons Ltd, MENCAP & IASSID
volume 57 part 9 september 2013
for providing helpful insights and advice on this
study. Financial support was provided by a grant of
the Marguerite-Marie Delacroix Foundation.
References
Arffa S. (2007) The relationship of intelligence to execu-
tive function and non-executive function measures in a
sample of average, above average, and gifted youth.
Archives of Clinical Neuropsychology 22, 969–78.
Barton B. & North K. (2004) Social skills of children with
neurofibromatosis type 1. Developmental Medicine and
Child Neurology 46, 553–63.
Barton B. & North K. (2007) The self-concept of children
and adolescents with neurofibromatosis type 1. Child:
Care, Health and Development 33, 401–8.
Billingsley R. L., Jackson E. F., Slopis J. M., Swank P. R.,
Mahankali S. & Moore B. D. (2003) Functional mag-
netic resonance imaging of phonologic processing in
neurofibromatosis 1. Journal of Child Neurology 18, 731–
40.
Brewer V. R., Moore B. D. & Hiscock M. (1997) Learning
disability subtypes in children with neurofibromatosis.
Journal of Learning Disabilities 30, 521–33.
Cawthon R. M., Weiss R., Xu G. F., Viskochil D., Culver
M., Stevens J. et al. (1990) A major segment of the neu-
rofibromatosis type 1 gene: cDNA sequence, genomic
structure, and point mutations. Cell 62, 193–201.
Clements-Stephens A. M., Rimrodt S. L., Gaur P. &
Cutting L. E. (2008) Visuospatial processing in children
with neurofibromatosis type 1. Neuropsychologia 46,
690–7.
Crawford J. R., Allan K. M. & Jack A. M. (1992) Short-
forms of the UK WAIS-R: regression equations and
their predictive validity in a general population sample.
British Journal of Clinical Psychology 31, 191–202.
Crawford J. R., Allum S. & Kinion J. E. (2008) An index-
based short form of the WAIS-III with accompanying
analysis of reliability and abnormality of differences.
British Journal of Clinical Psychology 72, 215–37.
Descheemaeker M. J., Ghesquiere P., Symons H., Fryns
J. P. & Legius E. (2005) Behavioural, academic and neu-
ropsychological profile of normally gifted Neurofibroma-
tosis type 1 children. Journal of Intellectual Disability
Research 49, 33–46.
Diaz-Asper C. M., Schretlen D. J. & Pearlson G. D.
(2004) How well does IQ predict neuropsychological
test performance in normal adults? Journal of the Inter-
national Neuropsychological Society 10, 82–90.
Dilts C. V., Carey J. C., Kircher J. C., Hoffman R. O.,
Creel D., Ward K. et al. (1996) Children and adoles-
cents with neurofibromatosis 1: a behavioral phenotype.
Journal of Developmental and Behavioral Pediatrics 17,
229–39.
 Journal of Intellectual Disability Research
885
M.-J. Descheemaeker et al. • Neuropsychological profile in NF1 adults
Duong T. A., Bastuji-Garin S., Valeyrie-Allanore L.,
Sbidian E., Ferkal S. & Wolkenstein P. (2011) Evolving
pattern with age of cutaneous signs in neurofibromatosis
type 1: a cross-sectional study of 728 patients. Dermatol-
ogy 222, 269–73.
Eldridge R., Denckla M. B., Bien E., Myers S., Kaiser-
Kupfer M. I., Pikus A. et al. (1989) Neurofibromatosis
type 1 (Recklinghausen’s disease). Neurologic and cog-
nitive assessment with sibling controls. American Journal
of Diseases of Children 143, 833–7.
Feldmann R., Denecke J., Grenzebach M., Schuierer G. &
Weglage J. (2003) Neurofibromatosis type 1: motor and
cognitive function and T2-weighted hyperintensities.
Neurology 61, 1725–8.
Ferner R. E. (2010) The neurofibromatoses. Practical Neu-
rology 10, 82–93.
Ferner R. E., Hughes R. A. & Weinman J. (1996) Intellec-
tual impairment in neurofibromatosis 1. Journal of the
Neurological Sciences 138, 125–33.
Friedman J. M. (1999) Epidemiology of neurofibromatosis
type 1. American Journal of Medical Genetics 89, 1–6.
Gutmann D. H., Aylsworth A., Carey J. C., Korf B.,
Marks J., Pyeritz R. E. et al. (1997) The diagnostic
evaluation and multidisciplinary management of neu-
rofibromatosis 1 and neurofibromatosis 2. JAMA 278,
51–7.
Hammes J. G. W. (1978) De Stroop Kleur-woord Test. Han-
dleiding. Swets & Zeitlinger, Lisse.
Heaton R. K., Chelune G. J., Talley J. L., Kay G. G. &
Curtiss G. (1993) Wisconsin Card Sorting Test Manual:
Revised and Expanded. Psychological Assessment
Resources, Odessa, FL.
Hofman K. J., Harris E. L., Bryan R. N. & Denckla M. B.
(1994) Neurofibromatosis type 1: the cognitive pheno-
type. Journal of Pediatrics 124, S1–8.
Huijbregts S. & De Sonneville L. (2010) Does cognitive
impairment explain behavioral and social problems of
children with Neurofibromatosis Type 1? Behavior Genet-
ics 41, 430–6.
Huijbregts S., Jahja R., De Sonneville L., de Breij S. &
Swaab-Barneveld H. (2010a) Social information
processing in children and adolescents with neurofi-
bromatosis type 1. Developmental Medicine and Child
Neurology 52, 620–5.
Huijbregts S., Swaab H. & De Sonneville L. (2010b) Cog-
nitive and motor control in Neurofibromatosis Type 1:
influence of maturation and hyperactivity-inattention.
Developmental Neuropsychology 35, 737–51.
Hyman S. L., Shores A. & North K. N. (2005) The nature
and frequency of cognitive deficits in children with neu-
rofibromatosis type 1. Neurology 65, 1037–44.
Hyman S. L., Arthur S. E. & North K. N. (2006) Learn-
ing disabilities in children with neurofibromatosis type 1:
© 2012 The Authors. Journal of Intellectual Disability Research © 2012 John Wiley & Sons Ltd, MENCAP & IASSID
volume 57 part 9 september 2013
subtypes, cognitive profile, and attention-deficit-
hyperactivity disorder. Developmental Medicine and Child
Neurology 48, 973–7.
Jett K. & Friedman J. M. (2010) Clinical and genetic
aspects of neurofibromatosis type 1. Genetics in Medicine
12, 1–11.
Johnson N. S., Saal H. M., Lovell A. M. & Schorry E. K.
(1999) Social and emotional problems in children with
neurofibromatosis type 1: evidence and proposed inter-
ventions. Journal of Pediatrics 134, 767–72.
Kaufman A. S., Ishikuma T. & Kaufman-Packer J. L.
(1991) Amazingly short forms of the WAIS-R. Journal of
Psychoeducational Assessment 9, 4–15.
Krab L. C., Aarsen F. K., Goede-Bolder A., Catsman-
Berrevoets C. E., Arts W. F., Moll H. A. et al. (2008)
Impact of neurofibromatosis type 1 on school perform-
ance. Journal of Child Neurology 23, 1002–10.
Krikorian R., Bartok J. & Gay N. (1994) Tower of London
procedure: a standard method and developmental data.
Journal of Clinical and Experimental Neuropsychology 16,
840–50.
Legius E., Descheemaeker M. J., Spaepen A., Casaer P. &
Fryns J. P. (1994) Neurofibromatosis type 1 in child-
hood: a study of the neuropsychological profile in 45
children. Genetic Counseling 5, 51–60.
Mascie-Taylor C. G. (1989) Spouse similarity for IQ and
personality and convergence. Behavior Genetics 19,
223–7.
Mascie-Taylor C. G. & Vandenberg S. G. (1988) Assorta-
tive mating for IQ and personality due to propinquity
and personal preference. Behavior Genetics 18, 339–45.
Mautner V. F., Kluwe L., Thakker S. D. & Leark R. A.
(2002) Treatment of ADHD in neurofibromatosis
type 1. Developmental Medicine and Child Neurology 44,
164–70.
Miatton M., Wolters M., Lannoo E. & Vingerhoets G.
(2004) Updated and extended Flemish normative data
of commonly used neuropsychological tests. Psychologica
Belgica 44, 189–216.
Moore B. D., Slopsis J. M., Schomer D., Jackson E. F. &
Levy B. M. (1996) Neuropsychological significance of
areas of high signal intensity on brain MRIs of children
with neurofibromatosis. Neurology 46, 1660–8.
Noll R. B., Reiter-Purtill J., Moore B. D., Schorry E. K.,
Lovell A. M., Vannatta K. et al. (2007) Social, emo-
tional, and behavioral functioning of children with NF1.
American Journal of Medical Genetics 143A, 2261–73.
North K. (2000) Neurofibromatosis type 1. American
Journal of Medical Genetics 97, 119–27.
North K., Joy P., Yuille D., Cocks N. & Hutchins P. (1995)
Cognitive function and academic performance in chil-
dren with neurofibromatosis type 1. Developmental Medi-
cine and Child Neurology 37, 427–36.
 Journal of Intellectual Disability Research
886
M.-J. Descheemaeker et al. • Neuropsychological profile in NF1 adults
North K., Hyman S. & Barton B. (2002) Cognitive defi-
cits in neurofibromatosis 1. Journal of Child Neurology
17, 605–12.
North K. N., Riccardi V., Samango-Sprouse C., Ferner R.,
Moore B., Legius E. et al. (1997) Cognitive function and
academic performance in neurofibromatosis. Consensus
statement from the NF1 Cognitive Disorders Task
Force. Neurology 48, 1121–7.
Pavol M., Hiscock M., Massman P., Moore I. B., Foorman
B. & Meyers C. (2006) Neuropsychological function in
adults with von Recklinghausen’s neurofibromatosis.
Developmental Neuropsychology 29, 509–26.
Pellicano E., Gibson L., Maybery M., Durkin K. &
Badcock D. R. (2005) Abnormal global processing along
the dorsal visual pathway in autism: a possible mecha-
nism for weak visuospatial coherence? Neuropsychologia
43, 1044–53.
Plaisted K., Saksida L., Alcántara J. & Weisblatt E. (2003)
Towards an understanding of the mechanisms of weak
central coherence effects: experiments in visual config-
ural learning and auditory perception. Philosophical
Transactions of the Royal Society of London. Series B,
Biological Sciences 358, 375–86.
Riccardi V. M. & Eichner J. E. (1986) Neurofibromatosis:
Phenotype, Natural History and Pathogenesis. Johns
Hopkins University Press, Baltimore, MD.
Rowbotham I., Pit-ten Cate I. M., Sonuga-Barke E. J. &
Huijbregts S. C. (2009) Cognitive control in adolescents
with neurofibromatosis type 1. Neuropsychology 23,
50–60.
Schrimsher G. W., Billingsley R. L., Slopis J. M. & Moore
B. D. (2003) Visual-spatial performance deficits in chil-
dren with neurofibromatosis type-1. American Journal of
Medical Genetics 120A, 326–30.
Schrimsher G. W., O’Bryant S. E., O’Jile J. R. & Sutker
P. B. (2008) Comparison of tetradic WAIS-III short
forms in predicting full scale IQ scores in neuropsychi-
atric clinic settings. Journal of Psychopathology and
Behavioral Assessment 30, 235–40.
© 2012 The Authors. Journal of Intellectual Disability Research © 2012 John Wiley & Sons Ltd, MENCAP & IASSID
volume 57 part 9 september 2013
Silverstein A. B. (1992) Two- and four-subtest short forms
of the Wechsler Adult Intelligence Scale – Revised.
Journal of Consulting and Clinical Psychology 50, 415–18.
Sternberg R. J. & Pretz J. E. (2005) Cognition and Intelli-
gence: Identifying the Mechanisms of the Mind. Cambridge
University Press, New York, NY.
Thienpont K. & Verleye G. (2004) Cognitive ability and
occupational status in a British cohort. Journal of Bioso-
cial Science 36, 333–49.
Thissen D., Steinberg L. & Kuang D. (2002) Quick and
easy implementation of the Benjamini-Hochberg proce-
dure for controlling the false positive rate in multiple
comparisons. Journal of Educational and Behavioral
Statistics 27, 77–83.
Uttner I., Wahllander-Danek U. & Danek A. (2003) Cog-
nitive impairment in adults with neurofibromatosis type
1. Fortschritte der Neurologie-Psychiatrie 71, 157–62.
Viskochil D., Buchberg A. M., Xu G., Cawthon R. M.,
Stevens J., Wolff R. K. et al. (1990) Deletions and a
translocation interrupt a cloned gene at the neurofi-
bromatosis type 1 locus. Cell 62, 187–92.
Wallace M. R., Marchuk D. A., Andersen L. B., Letcher
R., Odeh H. M., Saulino A. M. et al. (1990) Type 1
neurofibromatosis gene: identification of a large tran-
script disrupted in three NF1 patients. Science 249,
181–6.
Wechsler D. (2000) WAIS-III, Nederlandse bewerking.
Technische handleiding. The Psychological Corporation,
San Antonio, TX.
Wechsler D. (2002) WISC-III, Nederlandse bewerking. Han-
dleiding. The Psychological Corporation, London.
Zöller M. E. & Rembeck B. (1999) A psychiatric 12-year
follow-up of adult patients with neurofibromatosis type
1. Journal of Psychiatric Research 33, 63–8.
Zöller M. E., Rembeck B. & Backman L. (1997) Neu-
ropsychological deficits in adults with neurofibromatosis
type 1. Acta Neurologica Scandinavica 95, 225–32.
Accepted 19 September 2012
This document is a scanned copy of a printed document. No warranty is given about the
accuracy of the copy. Users should refer to the original published version of the material.