Males with Fragile X Syndrome (FXS) perform well below chronological age on measures of receptive and expressive vocabulary8,9,12 and morphosyntax2,5,11. Adult males with FXS have shown vocabulary scores similar to those of age- and cognitively-matched males with nonspecific forms of mental retardation and with autism2,9. Lexical skills in males with FXS have been shown to exceed nonverbal mental age8. Less is known about lexical development in females with FXS2. Past research has shown differences in receptive vocabulary and syntax in individuals with Downs Syndrome (DS)1,4, but similar performances in FXS across subtests of the Test for Auditory Comprehension of Language-R1. The Peabody Picture Vocabulary Test-R has been used as a measure of receptive language ability in FXS patients7. Data are needed to compare receptive vocabulary, especially as measured by the PPVT-III – the standard measure of receptive vocabulary, with other language skills and with verbal mental age in FXS adults. In fact, FXS is the most common cause of inherited mental retardation and is thought to affect 1 in 4,000 individuals in the general population13. Thus, thorough understanding of the language profile in FXS is crucial for delivery of language interventions and for proper design of clinical trials.

1. VOCABULARY COMPREHENSION IN FRAGILE X SYNDROME: #139
COMPARATIVE ANALYSES
Sue Ellen Krause*, Elizabeth Berry-Kravis§, Joanne Wuu§, Sue Leurgans§, Stephen J. Guter, Jr.†, Sandra S. Block‡, Jeff Salt†, Edwin Cook†, and Dominick Maino‡
*Krause Speech and Language Services, Chicago, §Rush University Medical Center, Chicago, †University of Illinois at Chicago, ‡Illinois College of Optometry, Chicago
Background Methods Results Conclusions
Males with Fragile X Syndrome (FXS) perform well below chronological age on measures of Subjects Comparison of AE Scores Between Tests • Vocabulary comprehension in our FXS adults was superior to overall
receptive and expressive vocabulary8,9,12 and morphosyntax2,5,11. Adult males with FXS • 42 adults (33 males, 9 females) with FXS undergoing baseline testing for language, verbal reasoning, and cognition.
PPVT PPVT PPVT PLS/CELF
have shown vocabulary scores similar to those of age- and cognitively-matched males with entry into a controlled clinical trial investigating the effect of CX516, an AMPA- vs. vs. vs. vs. • Receptive vocabulary as measured by the PPVT-III is not a representative
nonspecific forms of mental retardation and with autism2,9. Lexical skills in males with FXS benchmark of receptive or overall language skills in FXS.
modulating compound, on cognition and behavior in FXS. PLS/CELF SB SB-Verbal SB
have been shown to exceed nonverbal mental age8. Less is known about lexical Mean ± SD
development in females with FXS2.
• FXS defined by an expansion mutation in FMR1 with at least partial of the difference
3.1 ± 2.5 2.6 ± 2.5 1.2 ± 2.4 -0.5 ± 1.0
methylation (full mutation), consistent with a diagnosis of FXS by DNA Paired t-test p < 0.0001 p < 0.0001 p = 0.0022 p = 0.0013
Past research has shown differences in receptive vocabulary and syntax in individuals with analysis.
Downs Syndrome (DS)1,4, but similar performances in FXS across subtests of the Test for
Auditory Comprehension of Language-R1. The Peabody Picture Vocabulary Test-R has
• Inclusion criteria: age 18-50 years; measured IQ 20-85; normal hearing;
PPVT vs. PLS/CELF
Discussion
normal or corrected vision; stable medication regimen for 8 weeks prior to
been used as a measure of receptive language ability in FXS patients7. AE scores on the PPVT were significantly higher than those on the PLS/CELF
enrollment; a negative pregnancy test (female subjects) at enrollment; native • Unlike typically developing populations, the FXS population shows much
English speakers; no recent history of seizure, epilepsy, or syncope, an (p<0.0001). The difference averaged 3.1 ± 2.5 years, with a 5-10 year disparity
better ability in basic receptive vocabulary than in other areas of language
Data are needed to compare receptive vocabulary, especially as measured by the PPVT-III for some subjects - especially those with higher mental age.
– the standard measure of receptive vocabulary, with other language skills and with verbal
unresolved medical issue impacting performance, or behavioral dysfunction and cognition. Consistent with the known neural connectivity problem in FXS,
mental age in FXS adults. In fact, FXS is the most common cause of inherited mental sufficiently severe to preclude cooperation with testing. our findings likely reflect greater difficulty for FXS adults to process
retardation and is thought to affect 1 in 4,000 individuals in the general population13. Thus, • Recruited through the FXS Clinic, Rush University Medical Center, Chicago. information requiring recruitment of more diffuse brain regions. By
thorough understanding of the language profile in FXS is crucial for delivery of language • Informed written consent from either the subject or the parent/legal guardian
15
diffe
renc
e comparison, vocabulary comprehension is a relatively simple and more
PPVT AE (Years)
ear
interventions and for proper design of clinical trials. prior to participation. Assent was obtained in every case in which the subject
10-y localized task.
was not his/her own legal guardian. 10
nce
ffere
nc e • A possible decline in mental age with aging has been noted for FXS2,6. That
No di
5-ye
ar di
ffere
may partly contribute to the stunning disparity between receptive vocabulary
Subject Characteristics and other language/cognitive skills; however, the simplicity of the receptive
Purpose Total
(N=42)
5 vocabulary task is likely the primary source of the significant differences
observed in this study.
• To evaluate receptive vocabulary in FXS and determine whether receptive vocabulary Age Mean ± SD 26.4 ± 8.2
4 6 8 10
• The SB-Verbal included Picture Vocabulary and Oral Definitions, both
performance is commensurate with more global language and cognition:
(Range) (18 - 49) expressive language tasks. Literature on relative ability in receptive and
PLS/CELF AE (Years)
• To compare performance in receptive vocabulary and overall receptive/expressive Sex Male 33 expressive vocabulary in FXS males is mixed2,10. Our study does not allow for
language.
Female 9
PPVT vs. SB and SB-Verbal such a comparison, since SB-Verbal includes oral definition.
• To compare performance in receptive vocabulary and verbal and composite IQ.
Race Caucasian 39
The AE scores on the PPVT were also significantly higher than those on both • Abbeduto et. al. (2003) did not show a difference across subtests of the
African Am. 2
TACL-R in FXS. Our findings and theirs differ partly because our subjects
Hispanic 1 the SB (p<0.0001) and SB-Verbal (p=0.0022). The PPVT averaged 2.6 ± 2.5 were older and discrepancies in scores may increase with age. More likely,
• To compare overall receptive/expressive language and verbal and composite IQ. years higher than the SB and 1.2 ± 2.4 years higher than the SB-Verbal.
Stanford-Binet IQ Mean ± SD 44.4 ± 11.3 the different measures employed in the two studies (i.e., WC&R, TACL-R vs.
(Range) (36 - 75) PPVT-III) explain the different results.
High Functioning* Yes 13 • Children with DS perform better on receptive vocabulary than syntax by 1
No 29
15 e
year4. Differences increased with age in DS and in normal, mental age-
matched controls. The measurement domains preclude direct comparison to
ce 15 nc
dif feren ere
Autism Yes 22 ear diff
10-y
PPVT AE (Years)
PPVT AE (Years)
ar ce
(by ADOS & ADI) Spectrum 4
fere
nc e
10
-ye
diff
er en our study, but it appears that the magnitude of difference between vocabulary
No 15 5-ye
ar dif
feren
ce 5-y
ear
ce
comprehension and other language skills is larger in FXS adults than in the
Missing 1
Fragile X Syndrome (FXS) No dif
DS population.
10 10 er en
diff
No
*Defined as Stanford-Binet IQ ≥ 50
5
Prevalence 5
• Full mutation: 1 per 3600 males, 1 per 4000 females
• Premutation: 1 per 800 males, 1 per 259 females
Measures
• All subjects were tested individually on:
Implications for
• Most common known inherited form of MR • Peabody Picture Vocabulary Test-III, Form A (PPVT).
• Either Preschool Language Scale-4 (PLS) for those with a mental age
4 6
SB AE (Years)
8 10 2 4 6 8 10
SB-Verbal AE (Years)
12 14 16
Future Research
Characteristics of <6;0 (n=26), or Clinical Evaluation of Language Function-3 (CELF)
PLS/CELF vs. SB • The PPVT-III should not be used as a screening tool for language levels or
• Variable physical features: Long, wide, or protruding ears, long face, prominent jaw, high for those with a mental age of 6;0-8;11 (n=14) or ≥9;0 (n=2).
arched palate, macrocephaly, midfacial hypoplasia, epicanthal folds, prominent forehead. • The screening battery from the Stanford-Binet Intelligence Scale–IV The PLS/CELF differed significantly (p=0.001) from the SB, with the mean cognitive function in clinical studies.
• Cognitive deficits ranging from severe to very mild (SB): Vocabulary (Verbal Reasoning, SB-Verbal); Pattern Analysis PLS/CELF lower than the mean SB by 0.5 ± 1.0 years. The difference between • There is a need for development of efficient tools to measure receptive and
• Speech and language deficits (Abstract Visual Reasoning); Quantitative (Quantitative Reasoning); overall language and cognition as found in these data, albeit statistically expressive language for vocabulary, syntax, concepts, and phonological
• Fine-motor deficits Bead Memory (Short Term Reasoning). significant, is likely not clinically relevant in the adult FXS population. processing in the FXS population.
• Prominent behavioral issues • Rationale for use of PLS/CELF Total Scores:
• There was a high correlation between the PLS-AC, PLS-EC, and PLS- 10
Medical Problems Total Score (Spearman rank correlation, r>0.80, p<0.0001), and all three ren
c e
PLS/CELF AE (Years)
iffe
• Recurrent otitis media
• Dental malocclusion
• Hypotonia
• Anxiety disorders
• Visual abnormalities
• Early seizure disorders
showed similar relationship with the PPVT.
• On the CELF, an AE score is only available on the Total Test. The raw
8
5-y
ea
rd
e
References
nc
• Growth disorders scores of the Receptive Language component strongly correlated with No
dif
fere
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