Mental, Motor, and Language Development of Toddlers withNeurofibromatosis Type 1

Jennifer Lorenzo, MPsych, Belinda Barton, PhD, Maria T. Acosta, MD, and Kathryn North, MD

Objective To examine the mental, motor, and language development of toddlers with neurofibromatosis type 1(NF1).Study design In this cross-sectional study, 39 toddlers with NF1 (aged 21-30 months) and 42 age-matched con-trol children were assessed using the Bayley Scales of Infant Development, Second Edition. Basic vocabulary wasassessed with the language subtests from the Wechsler Preschool and Primary Scale of Intelligence, Third Edition.Parents completed questionnaires evaluating the children’s expressive language, behavior, and executive function-ing. The c2 test, independent t test, Mann-Whitney U test, and analysis of covariance were used to examine differ-ences between the two groups.Results The toddlers with NF1 had significantly poorer mental and motor development than the control partici-pants. Parental responses indicated that most of the children with NF1 had delayed language skills. No differencesin behavior and executive functioning were noted between the two groups of children.Conclusions Children with NF1 as young as age 30 months demonstrate early signs of mental, motor, and lan-guage difficulties. Age 2 years may be the appropriate time to perform an initial developmental assessment to iden-tify mental, motor, and language impairments in children with NF1. (J Pediatr 2011;158:660-5).

Neurofibromatosis type 1 (NF1) is an autosomal dominant disorder with an estimated prevalence of 1 in 3000 individ-uals.1 NF1 typically presents with neurocutaneous stigmata, such as caf�e-au-lait macules, axillary freckling, and neu-rofibromas. Affected children are monitored for associated complications, including optic pathway tumors, scoliosis,

and hypertension.2 The most commonly reported neurologic complications of NF1, particularly in childhood, are learning dis-abilities and academic underachievement.2 Even though the general intelligence of school-aged children with NF1 is typicallywithin the low average to average range, up to 65% exhibit specific cognitive difficulties that negatively impact their academicperformance.2 Widespread problems have been found in visuospatial functioning, executive functioning, expressive and recep-tive language, fine motor skills, reading, spelling, and mathematics.3

Most previous studies examining cognitive function in children with NF1 have focused on school-aged children, age 8-16years. Few studies have included children under age 6 years, and only 3 studies have reported specifically on cognitive function-ing in this preschool age group. Legius et al4 grouped children with NF1 into 3 age groups: 17 months to 4 years (n = 7), 4-6years (n = 7), and 6-16 years (n = 31). In the youngest age group, 6 of the 7 children demonstrated delays in language andmotorskills, with 4 of the 7 children having a mild developmental delay. In the 4- to 6-year group, general intellectual functioning wasin the average range, with significantly better verbal abilities than nonverbal abilities. A study of toddlers with NF1 (n = 90;mean age, 34 months) found impaired cognitive abilities with abnormal neuromotor and perceptual motor development com-pared with normative data.5 Finally, a study of 4- to 5-year-old children with NF1 (n = 26) conducted in our center foundgeneral intellectual functioning in the average range, but significantly lower than in healthy peers.6

These studies suggest that childrenwithNF1whoare at risk for cognitive deficitsmaybe identified at an early age; however, littleis known about these children’s specific cognitive and motor phenotype and its impact on early learning and development. The

From the Institute for Neuroscience and MuscleResearch (J.L., B.B., K.N.) and Children’s HospitalEducation Research Institute (B.B.), The Children’sHospital at Westmead, Westmead, New South Wales,Australia; Department of Neurology, Children’s NationalMedical Center,Washington, DC (M.A.); and Discipline ofPaediatrics and Child Health, Faculty of Medicine,University of Sydney, Sydney, New South Wales,Australia (J.L., B.B., K.N.)

Supported by the Department of Defense Neurofibro-matosis Research Program, managed by the US ArmyMedical Research and Materiel Command (USAMRMC:Award no. W81XWH-04-1-0510). The authors declare noconflicts of interest.

0022-3476/$ - see front matter. Copyright ª 2011 Mosby Inc.

All rights reserved. 10.1016/j.jpeds.2010.10.001

BASC-II Behavior Assessment System

for Children, Second

Edition–Preschool

Version

BRIEF-P Behavior Rating Inventory of

Executive Functioning–

Preschool Version

BRS Behavior Rating Scale

BSID-II Bayley Scales of Infant

Development, Second

Edition

GLC Global Language

Composite

IQR Interquartile range

MacArthur

CDI MacArthur Communicative

Development Inventories

Words and Sentences

NF1 Neurofibromatosis type 1

SD Standard deviation

SES Socioeconomic status

T2H T2 hyperintensities

TABS Temperament and Atypical

Behavior Scale

TRI TemperamentandRegulatory Index

WPPSI-III Wechsler Preschool and Primary

Scale of Intelligence, Third

Edition, Australian Adaptation

660

Vol. 158, No. 4 � April 2011

present study was conducted to examine the mental, motor,and language development of toddlers with NF1. We hypoth-esized that toddlers with NF1 will have poorer mental, motor,and language development compared with healthy peers.

Methods

Children who satisfied the National Institutes of Health diag-nostic criteria for NF17 were recruited prospectively from theNeurogenetics Clinic at The Children’s Hospital atWestmead.A pediatric neurologist or geneticist confirmed the diagnosis ofNF1 in all children. Eight children with NF1 were excluded(one child who was born premature with hearing loss, 3 chil-dren with inadequate English skills, 3 children with optic glio-mas, and one child whose sibling was already enrolled in thestudy). The childrenwithNF1were enrolled in anongoing lon-gitudinal study involving regular neurodevelopmental assess-ments up to age 7 years. Here we report the cross-sectionaldata obtained from scheduled assessments performed at age21 months and age 30 months in these children.

Control children (matched by age and mother’s years ofeducation) were recruited from various sources, includingunaffected siblings of children with sporadic NF1 seen inthe Neurogenetics Clinic (with unaffected parents) who didnot have a sibling enrolled in the study, children attendingpreschools in the Sydney metropolitan area, and advertise-ments placed in local community newspapers. Childrenwith intracranial pathology, visual or hearing problems, orother medical conditions were excluded. Parents were re-quired to be fluent in the English language, and all childrenwere monolingual (English) speakers.

This study was approved by The Children’s Hospital atWestmead’s Ethics Committee and the US ArmyMedical Re-search andMateriel Command. Eligible families that attendedthe Neurogenetics Clinic was sent an information sheet aboutthe study. A follow-up phone call was made to ascertain thefamily’s willingness to enroll in the study. Directors of pre-schools were randomly selected from the local metropolitanarea and weremailed an invitation to participate, an informa-tion sheet, and a preference form to complete and return in-dicating whether or not they would be willing to distributeinformation about the study to families. Preschool directorswho agreed to distribute information were mailed parent in-formation sheets, which they then forwarded to families. Inaddition, advertisements were placed in local newspapers ask-ing interested families to phone the investigators for furtherinformation. Informed signed consent was obtained fromall participants. Each child was assessed by a psychologist atthe hospital. Parents were asked to complete several question-naires pertaining to their child’s development.

MeasuresMental and Motor Skill Development. Developmentalfunctioning was assessed using the Bayley Scales of Infant De-velopment, Second Edition (BSID-II).8 Index scores were de-rived for the mental and motor scales. The mental scaleincludes items that assess problem solving; memory; knowl-

edge of numbers, shapes, and colors; emerging language; andsocial skills. The motor scale assesses fine and gross motorskills, such as sitting, crawling, walking, and manipulationof writing implements and small objects. The examinerused the Behavior Rating Scale (BRS) to rate the child’s atten-tion, orientation/engagement, emotional regulation, andmotor quality during testing. BRS scores were classified asnormal (>26th percentile), questionable (11th-25th percen-tile), or nonoptimal (<10th percentile), in accordance withthe test manual.

Basic Vocabulary. The basic vocabulary skills of the 30-month-old participants were assessed with the ReceptiveVocabulary and Picture Naming subtests of the WechslerPreschool and Primary Scale of Intelligence, Third Edition,Australian Adaptation (WPPSI-III).9 A General LanguageComposite (GLC) score was derived from these subtests.

Expressive Language. The MacArthur CommunicativeDevelopment Inventories Words and Sentences (MacArthurCDI)10 was used to obtain parental assessments of theirchild’s vocabulary knowledge and grammar skills. Sex-specific percentile ranks were derived for the total numberof words produced, the use of irregular nouns and verbs(ie, words that do not follow letter-to-sound rules, eg,shoe), and level of sentence complexity. Percentiles were clas-sified as above average (76-100), average (25-75), or belowaverage (0-24). Children aged 30 months were classified as‘‘late-talkers’’ if their productive vocabulary score was at orbelow the 10th percentile.10,11 Parents were also asked towrite down 3 of the longest sentences their child had spokenrecently, providing a qualitative sample of speech.

Temperament. The Temperament and Atypical BehaviorScale (TABS)12 was completed by parents to determine theirchild’s risk of atypical self-regulatory behavior. The Temper-ament and Regulatory Index (TRI) was determined based onthe following factors: detached, hypersensitive/active, under-reactive, and dysregulated problem behaviors. TRI scoreswere classified as normal, at risk, or atypical in accordancewith the test manual.

Emotional and Behavioral Functioning. The BehaviorAssessment System for Children, Second Edition–PreschoolVersion (BASC-II)13 was used to assess parents’ perceptionsof their child’s emotional and behavioral adjustment. T-scores were derived for the following indices: Hyperactivity,Aggression, Anxiety, Depression, Somatization, Atypicality,Withdrawal, Attention Problems, Adaptability, Social Skills,Activities of Daily Living, and Functional Communication.From these indices, composite T-scores were derived forthe following: Externalizing Problems, Internalizing Prob-lems, Behavioral Symptoms Index, and Adaptive Skills. TheBASC-II was administered at age 30 months only.

Executive Functioning. The Behavior Rating Inventoryof Executive Functioning–Preschool Version (BRIEF-P)14

661

THE JOURNAL OF PEDIATRICS � www.jpeds.com Vol. 158, No. 4

was used to assess parents’ perceptions of their child’s exec-utive functioning. T-scores were derived for the followingscales: Inhibit, Shift, Emotional Control, Working Memory,and Planning/Organization. From these scales, 3 overlappingsummary index scores—Inhibitory Self-Control, Flexibility,and EmergentMetacognition—and a Global Executive Com-posite were derived. The BRIEF-P was administered at age 30months only.

Socioeconomic Status. Parents’ socioeconomic status(SES) was assessed using the Hollingshead Four-Factor Indexof Social Status.15

Statistical AnalysesData obtained from the 30-month assessment or from the 21-month assessment (if the child had not been assessed at 30months) were analyzed using SPSS version 17 (SPSS, Chi-cago, Illinois). Asymmetrically distributed data are reportedasmedian and interquartile range (IQR). Differences betweenthe two groups for categorical variables were examined usingthe c2 test. Differences between the two groups for continu-ous variables were examined using the independent t test, orthe Mann-Whitney U test when scores were asymmetricallydistributed. One-way analysis of covariance was used to ana-lyze mental performance scores, using SES as a covariate. Forthe BRIEF-P, BASC-II, WPPSI-III, and TABS, only compos-ite or index scores were analyzed, to control the type I errorrate. In addition, the Holm procedure (a modified Bonfer-roni procedure) was applied to control the error rate.

Completion Rate for MeasuresMental and motor development scores could not be obtainedin 3 children (two with NF1 and one control, who were un-cooperative), a motor development score could not be ob-tained for 3 children with NF1 (one uncooperative, onefatigued, and one distracted), and a mental developmentscore could not be obtained for two control children (one in-attentive and one uncooperative) and one child with NF1(distracted). Some children were unable to complete bothsubtests of the WPPSI-III (4 with NF1, 2 controls) or couldcomplete only one subtest (4 with NF1, 3 controls); conse-quently, a GLC score could not be calculated for these pa-tients. Not all parents completed the BRIEF-P (4 NF1parents did not complete; 3 NF1 parents and one control par-ent partially completed), the BASC-II (5 NF1 parents did notcomplete; 6 NF1 parents and one control parent partiallycompleted), the TABS (5 NF1 parents and one control parentdid not complete; 4 control parents partially completed), orthe MacArthur CDI (6 NF1 parents did not complete; 5 NF1parents and 9 controls did not complete the longest-sentences section).

Results

A total of 39 children with NF1 (6 at age 21 months and 33 atage 30 months) and 42 control children (4 at age 21 months

662

and 38 at age 30 months) were assessed. The median age inboth groups was 30 months (IQR, 0 months). The NF1 groupcomprised 24 sporadic cases (62%) and 15 familial cases(38%) of NF1, with 22 males (56%) and 17 females (44%).The control group comprised 25 males (60%) and 17 females(40%). There was no significant difference between the twogroups in terms of sex (c2 = 0.003; P = .95) or SES (mean� standard deviation [SD]; NF1, 36.18 � 13.98; controls,41.52 � 12.22; t(79) = -1.84, P = .07).The children with NF1 had significantly poorer mental and

motor development compared with the control children(Table I). In the NF1 group, the distribution of the mentaldevelopment scores was skewed slightly to the left. Therewas a significant difference in mental development betweenthe two groups after controlling for SES (F(1,72) = 14.35; P <.0001; partial h2 = 0.17), which was a marginally significantcovariate (P = .053). Approximately 33% of the childrenwith NF1 and 5% of the control children had a mentaldevelopment score in the mildly delayed range (Table II).Of the 33 children with NF1 in whom both mental and

motor development scores were available, 6 (18%) hadboth scores in the mildly delayed range. The majority ofBRS scores for the children were within the normal range(Table II). Children with NF1 had significantly poorerbasic language abilities than control children, as reflectedby lower GLC scores (Table I). No child’s mental, motor,or language performance was significantly delayed (ie,index score <70).More than 70% of the children with NF1 demonstrated

below-average performance in each of the following expres-sive language domains: irregular words, sentence complexity,and vocabulary production (Table II). The difference inperformance between the groups was significant forirregular words (c2 = 7.85; P = .020), sentence complexity(c2 = 16.69; P #.0001), and vocabulary production (c2 =10.66; P = .005). At the 30-month assessment, 14 childrenwith NF1 (52%) and 11 controls (29%) were classified aslate-talkers. However, there were no statistically significantdifferences between the two groups in the percentage oflate-talkers (c2 = 3.50; P = .06) or in the length of thelongest sentence spoken (Table I).Mean BRIEF-P and BASC-II scores were in the normal

range for both the NF1 and control goups (Table I). Therewere no significant differences between the two groups inBRIEF-P index, BRIEF-P composite, or BASC-II compositescores (Table I). According to TABS TRI scores (reportedin Table II), most of the children in both groups exhibitednormal self-regulation/temperament.

Discussion

This study focused on the mental, motor, and language skillsof toddlers with NF1. Consistent with our hypothesis, youngchildren with NF1 had significantly poorer mental develop-ment compared with their healthy peers. The average mentaldevelopment score of the NF1 group was in the low-average

Lorenzo et al

Table I. Mean BSID-II, WPPSI-III, BRIEF-P, BASC-II, and MacArthur CDI scores in the NF1 and control groups

NF1 Controls

Measure n Mean SD n Mean SD P

BSID-IIMental Development Index 39 88.50* 17† 36 101.90 11.02 <.0001z

Psychomotor Development Index 41 91.79 10.19 34 106.27 11.09 <.0001z

WPPSI-IIIReceptive Vocabulary 29 9.00* 4† 34 12.18 2.86 NCPicture Naming 25 9.16 3.00 35 12.00* 5† NCGLC 25 92.00* 27† 33 110.94 2.64 .002z

BRIEF-P T-scoreInhibit 27 48.00* 15† 38 50.29 10.09 NCShift 28 44.00* 15† 38 44.00* 17† NCEmotional Control 28 38.50* 18† 38 46.13 7.72 NCWorking Memory 26 55.00* 14† 38 54.50* 25† NCPlan/Organize 28 49.86 14.56 37 51.27 12.21 NCInhibitory Self-Control Index 27 44.00* 17† 38 48.37 9.05 .15Flexibility Index 28 43.00* 15† 38 43.00 12† .66Emergent Metacognition Index 26 49.50* 26† 37 53.57 12.08 .58Global Executive Composite 26 48.73 13.87 37 50.16 11.36 .66

BASC-II T-scoreHyperactivity 27 46.78 10.05 38 50.82 8.90 NCAggression 28 44.00* 6† 38 49.00* 9† NCAnxiety 24 41.00* 10† 37 49.00* 12† NCDepression 27 46.00* 11† 38 47.00 8.74 NCSomatization 27 46.96 9.49 38 50.11 8.45 NCAtypicality 28 45.50* 11† 38 51.00* 12† NCWithdrawal 28 43.00* 11† 38 47.84 8.47 NCAttention Problems 28 51.43 8.79 38 49.42 8.73 NCAdaptability 28 54.29 9.81 38 53.58 10.29 NCSocial Skills 27 44.85 8.67 38 49.08 8.88 NCActivities of Daily Living 25 41.00* 15† 38 44.82 6.49 NCFunctional Communication 22 42.59 7.71 38 46.84 6.69 NCExternalizing Problems 27 44.96 7.08 38 51.00* 10† .06Internalizing Problems 24 43.50 8.75 37 47.81 9.28 .08Behavior Symptom Index 27 45.85 8.02 38 49.47 8.80 .10Adaptive Skills 24 46.17 8.13 38 48.21 7.63 .32

MacArthur CDI Longest Sentence 28 4.29 2.71 33 5.74 3.25 .07

NC, not calculated.*Median.†IQR.zP < .001.

April 2011 ORIGINAL ARTICLES

range and was approximately 1 SD lower than the controls. Atthe 30-month assessment, common difficulties seen in theNF1 group included problemswith early number recognition,discrimination of shapes, naming colors, early drawing skills,and simple visuoconstructional abilities. The children withNF1 also had difficulties with the basic comprehension andexpressive language tasks of the BSID-II mental scale.

Our results are comparable with findings reported by Sa-mango-Sprouse5 and consistent with previous studies thatfound decreased intellectual functioning, 1 SD below norma-tive mean values, in school-aged children with NF1.2,3 In oursample, approximately 31% of the children with NF1 hada mental development score in the mildly delayed range.This is lower than the 57% rate reported by Legius et al4 ina sample of children aged 17 months to 4 years; however,their findings should be interpreted with caution given theirsmall sample size.

In the present study, the children with NF1 had signifi-cantly poorer motor skills compared with control children.Motor development was below average in approximatelyone-third of the children with NF1. Young children withNF1 presented with amyriad of fine and gross motor difficul-

Mental, Motor, and Language Development of Toddlers with Neu

ties. They had difficulty with many age-appropriate motortasks at the 30-month assessment, including walking back-ward close to a line, walking at least 4 steps on tiptoe, imitat-ing postures and hand movements, stopping from a full run,swinging the leg to kick a ball, jumping, grasping a pencil, andexhibiting hand–eye coordination when throwing.The motor difficulties seen in our NF1 group are in agree-

ment with those reported in previous studies.4,5 Motor dys-function in NF1 (particularly gross motor function) hasnot been studied extensively. School-aged children withNF1 have poorer performance in tasks assessing fine motorcoordination, manual dexterity, and balance skills.16,17 Verylittle is known about the potential causes of motor dysfunc-tion in NF1. It has been posited that T2 hyperintensities(T2H) may be associated with poor motor functioning.T2H are thought to represent developmental abnormalitiesof myelination and tend to resolve with age.18 School-agedchildren with NF1 and T2H have poorer fine motor coordi-nation than those without T2H.16,19 Moore et al16 reportedan association between T2H in the thalamus and poor finemotor coordination. To date, no other studies have exam-ined the relationship between the location of T2H and motor

rofibromatosis Type 1 663

Table II. Classification of scores in the NF1 and controlgroups

NF1,n (%)

Controls,n (%)

Mental Development IndexMildly delayed (70-84) 11 (31) 2 (5)Normal (85-114) 24 (67) 33 (85)Above normal (>115) 1 (3) 4 (10)

Psychomotor Development IndexMildly delayed (70-84) 9 (27) 1 (2)Normal (85-114) 25 (73) 34 (83)Above normal (>115) 0 (0) 6 (15)

BRSNonoptimal 2 (6) 1 (2)Questionable 8 (22) 7 (17)Normal 26 (72) 34 (81)

MacArthur CDI–Irregular WordsBelow average 24 (73) 17 (40)Average 7 (21) 18 (43)Above average 2 (6) 7 (17)

MacArthur CDI–Sentence ComplexityBelow average 25 (78) 13 (32)Average 7 (22) 22 (54)Above average 0 (0) 6 (14)

MacArthur CDI–Vocabulary ProductionBelow average 27 (82) 19 (45)Average 4 (12) 18 (43)Above average 2 (6) 5 (12)

TABS TRIAtypical 7 (20) 1 (3)At risk 3 (9) 5 (13)Normal 24 (71) 31 (84)

THE JOURNAL OF PEDIATRICS � www.jpeds.com Vol. 158, No. 4

function. A high percentage of children with NF1 (mean age,8 years) were found to have T2H in the basal ganglia, cerebel-lum/brainstem, and thalamus16—all regions of the brain as-sociated with motor function.20 There have been nosystematic studies of the frequency of T2H in very youngchildren with NF1, given that magnetic resonance imagingin children age <6 years requires general anesthesia andthis is not performed routinely in these children. It is possiblethat T2H may contribute to poor motor skills; however, fur-ther investigations are needed to clarify this relationship. Inaddition, the weak muscle tone in children with NF15 mightcontribute to impaired motor function. Muscle weakness canaffect children’s ability to use their upper and lower limbsand to bear weight, which can lead to delays in achieving am-bulation skills, such as rolling over, crawling, climbing onsteps, and walking independently.21

We found significant differences in early language skills be-tween our NF1 and control groups. Parental responses indi-cated that the majority of children with NF1 (>70%) hadbelow-average scores for productive vocabulary size, use of ir-regular nouns and verbs, and sentence complexity (measure ofmorphosyntax). Delays in language development, particularlyinmorphology and articulation, havebeen reported in toddlerswith NF1.4,5 Thompson et al22 examined the speech and lan-guage skills of 19 children with NF1 (age 3-5 years) and foundthat 32% had articulation difficulties, 37% had a receptive lan-guage delay, and 37% had a specific expressive language delay.

Mental, motor, and language impairments can be de-tected in very young children with NF1 (at �2½ years).

664

The BSID-II is a useful clinical tool for identifying theachievement of developmental milestones or delays in chil-dren with NF1. However, whether low mental developmen-tal scores are definitive predictors of future intellectualfunctioning is unclear. The BSID-II is a ‘‘developmentallyordered checklist of complex criterion behaviors’’23 anddoes not assess specific cognitive functions. In addition,the reliability of BSID-II as a predictor of later IQ appearsto be greater the older the child is at the time of testing, par-ticularly after age 2 years.24 This may be due in part to thefact that perceptual motor skills, as opposed to mental skills,are mostly assessed by earlier items on the mental scale.25 Inaddition, 2 years of age is a critical transition period in cog-nitive development, during which skills in symbolic func-tion, language development, and early concept formationemerge.26,27 Two-year-old children develop the capacity tocreate mental representations of reality based on objectsand past events.28 They begin to solve problems symboli-cally instead of by trial and error, as well as to engage in de-ferred imitation (the ability to remember and mimic actionsof others who are not immediately present) and pretendplay.28 Also at this age, children’s productive vocabulary ex-pands, they develop word combinations, and they are ableto follow simple instructions.28 BSID-II scores are morepredictive of future intellectual functioning in childrenwith atypical development than in normally developingchildren.29 Nonetheless, Blaga et al30 examined the mentaldevelopment and language skills of 226 healthy childrenover time and found that BSID-II scores were predictiveof later measures of intellectual functioning, reflecting a con-tinuity and stability of cognitive functioning in healthy chil-dren between late infancy (12 months) and the preschoolperiod (48 months). Mental developmental assessments atspecific ages, particularly from age 2 years and up, may pro-vide crucial information about the developmental mile-stones of infants and toddlers with NF1. We will continueto follow the cognitive development of our NF1 cohort upto age 7 years.Our findings have some important clinical implications

for parents and clinicians caring for young children withNF1. Monitoring children’s fine and gross motor milestonesis imperative. In the first 2 years of life, children ascertain a va-riety of sequential motor skills.31 Abnormalities in muscletone and reflexes, as well as difficulties mastering tasks thatrequire motor coordination (eg, buttoning clothes, catchinga ball, riding a tricycle), may be ‘‘red flags’’ that warrant clin-ical attention and further investigation in infants and tod-dlers with NF1.32

Early intervention programs have beneficial effects on themotor development of young children, particularly those inhigh-risk groups.33 Therefore, early intervention programsthat target specific skills and their general motor developmentmay improve the motor functioning of children with NF1.Of the expressive language domains assessed by the Mac-

Arthur CDI, the most common problem seen in the NF1group was their limited productive vocabulary. A productivevocabulary score at or below the 10th percentile at age 24

Lorenzo et al

April 2011 ORIGINAL ARTICLES

months has been used previously to classify children as late-talkers.10,11 Late-talkers may be at risk for later language im-pairment.10 In this study, we used the same cutoff percentilefor children at the 30-month assessment and found that 50%of infants with NF1 were classified as late-talkers. In childrenaged 24months, referral to a speech pathologist for a languageskills assessment is recommended if the child uses fewer than50 words or is not combining words, and parents are con-cerned about the child’s language ability; or if the child hashad 6 or more ear infections during the first 2 years of life.34

Our study has some limitations. First, because the BSID-IIprovides a general psychomotor development index score, wecould not distinguish between fine and gross motor impair-ments. A later edition of the BSID is now available that givessubtest scores for these domains35; unfortunately, this ver-sion was not available at the time of study recruitment. Sec-ond, formal assessment of the children’s language skills bya speech pathologist would have been valuable.

In summary, our findings indicate that toddlers with NF1exhibit early signs of mental, motor, and language difficultiescompared with healthy peers. Early identification of difficul-ties is crucial for improving developmental outcomes in boththe short term and the long term. Age 2 years may be the ap-propriate time to perform an initial developmental assess-ment to identify mental, motor, and language impairmentsin children with NF1. Earlier identification allows for earlierintervention, which is more likely to ameliorate the negativeimpact of cognitive and motor dysfunction associated withNF1, promote the conditions necessary for healthy well be-ing, and improve the developmental trajectory of childrenwith NF1. n

Submitted for publication May 16, 2010; last revision received Aug 11, 2010;

accepted Oct 4, 2010.

Reprint requests: Professor Kathryn North, MD, Institute for Neuroscience and

Muscle Research, The Children’s Hospital at Westmead, Locked Bag 4001,

Westmead, New South Wales, 2145, Australia. E-mail: kathryn@chw.edu.au

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