Abstract

Boys with fragile X syndrome with (n = 49) and without (n = 33) characteristics of autism spectrum disorder, boys with Down syndrome (39), and typically developing boys (n = 41) were compared on standardized measures of receptive vocabulary, expressive vocabulary, and speech administered annually over 4 years. Three major findings emerged. Boys with fragile X without autism spectrum disorder did not differ from the younger typically developing boys in receptive and expressive vocabulary and speech production when compared at similar levels of nonverbal cognitive skills. Boys with fragile X without autism spectrum disorder and typically developing boys had higher receptive vocabulary and speech production than did boys with Down syndrome. There were mixed patterns of results for the boys with fragile X and characteristics of autism spectrum disorder.

In this study, we compared boys with fragile X syndrome (who were classified as having or not having characteristics of autism spectrum disorder) to boys with Down syndrome and typically developing boys to determine whether the groups showed similar patterns of receptive vocabulary, expressive vocabulary, and speech acquisition across varying levels of nonverbal ability. Given the differential impact of gender on development in fragile X syndrome, all participants in this study were boys. We targeted receptive and expressive vocabulary as well as speech production in this research because these communication areas have been reported to be affected in both syndromes, from key foundational skills for later speech and language development, and can be measured reliably with standardized tests. Though many children with fragile X syndrome have autism spectrum disorders or characteristics of autism (Bailey, Hatton, & Skinner, 1998; Dykens & Volkmer, 1997; Hagerman, 2002), there is a lack of research in which investigators have examined the relationship between autism status and speech and language skills within fragile X syndrome. Consequently, another contribution of the present study is the comparison of the communication skills of children with fragile X syndrome with and without autism spectrum disorder.

Fragile X syndrome, an X-linked genetic condition, occurs in 1 of every 4,000 individuals (Crawford, Acuna, & Sherman, 2001; Turner, Webb, Wake, & Robinson, 1996). Fragile X Mental Retardation Protein (FMRP) is produced by the Fragile X Mental Retardation-1 gene and is believed to be essential for normal brain development and functioning (Devys, Lutz, Rouyer, Bellocq, & Mandel, 1993; Jin & Warren, 2003). In individuals with full mutations, the FMR1 gene becomes methylated (shuts down) and, as a consequence, no FMR1 protein (FMRP) is produced. The resulting deficiency appears to be responsible for the physical and neurodevelopmental characteristics of individuals with fragile X syndrome. The current literature on the communication skills of this population is based primarily on data from adolescent and adult males, case studies, and studies of small numbers of children. Difficulties in grammar, vocabulary, pragmatics, and speech development have been reported in adolescents and adults with fragile X syndrome, with grammar, vocabulary, and speech greatly delayed relative to chronological age (CA) expectations and more similar to developmental level expectations (Abbeduto et al., 2003; Madison, George, & Moeschler, 1986; Palmer, Gordon, Coston, & Stevenson, 1988; Sudhalter, Scarborough, & Cohen, 1991). Although there are considerable individual differences, researchers have reported that males with fragile X syndrome have moderate to severe delays in communication skills, greater delays in expressive compared to receptive language, repetitive speech and tangential language, and poor speech intelligibility in conversation (Abbeduto & Hagerman, 1997; Belser & Sudhalter, 2001; Newell, Sanborn, & Hagerman, 1983; Paul, Cohen, Breg, Watson, & Herman, 1984; Philofsky, Hepburn, Hayes, Hagerman, & Rogers, 2004; Rice, Warren, & Betz, 2005; Roberts, Mirrett, & Burchinal, 2001; Sudhalter & Belser, 2001).

There are few studies in which investigators examined whether the receptive and expressive vocabulary levels and speech skills of boys with fragile X syndrome are comparable to typically developing children at similar nonverbal cognitive levels, although a few researchers did conduct such comparisons in adolescents and adults. Abbeduto and colleagues (2003) found that 13 male and 6 female adolescents and adults with fragile X syndrome performed similarly to typically developing nonverbal cognitive matches on the Word Classes and Relations subtest of the Test of Auditory Comprehension of Language-Revised (Carrow-Woolfolk, 1985), a measure of receptive vocabulary. Sudhalter, Maranion, and Brooks (1992) reported that 11 boys and adult males with fragile X syndrome used a greater number of semantically incorrect words on a nonstandardized sentence completion test than did typically developing individuals of the same MA. The inconsistency of these findings may be at least partly due to the fact that the tasks are very different; a sentence completion task may place greater cognitive and linguistic demands on the retrieval of lexical items and on their formulation and production than would a receptive vocabulary task. Speech production in the single-word utterances of males with fragile X syndrome, as measured by the Goldman Fristoe Test of Articulation-2 (Goldman & Fristoe, 1969, 2000), is reported to be similar to younger, developmentally similar children (Hansen, Jackson, & Hagerman, 1986; Palmer et al., 1988; Prouty et al., 1988; Roberts et al., 2005).

Given the limited number of investigations on vocabulary and speech and the conflicting findings of Abbeduto and colleagues (2003) and Sudhalter and colleagues (1992), further clarification of the relationship between nonverbal cognition and vocabulary and speech levels is needed in children with fragile X syndrome. The present study expands previous work from this research group (Roberts et al., 2005) in phonology in children with fragile X syndrome; in the present study we examined age equivalent scores on a standardized speech test according to varying levels of MA and adding repeated measures of speech production over time.

The presence of autism in boys with fragile X syndrome may further affect communicative development. This is accentuated by the fact that the diagnosis of autism spectrum disorder requires language deficits (American Psychiatric Association, 2000). It is estimated that 15% to 25% of individuals with fragile X syndrome are diagnosed with autism (Bailey et al., 1998; Dykens & Volkmer, 1997; Hagerman, 2002), and 5.5% of males with autism test positive for fragile X syndrome (Dykens & Volkmer, 1997; Hagerman, 2002). Although in a few recent studies investigators have reported a relationship between autism status and overall communication development among children with fragile X syndrome, no studies were focused specifically on vocabulary or speech as outcomes. In a study of preschool- and school-age boys with fragile X syndrome, Bailey and colleagues (1998, 2001) found that as the number of characteristics of autism increased, communication skills decreased. Two recent studies of preschoolers found that children with fragile X syndrome and autism scored lower in receptive and overall language (Rogers, Wehner, & Hagerman, 2001) and expressive language (Philofsky et al., 2004), as measured by the Receptive and Expressive Language Scales from the Mullen Scales of Early Learning (Mullen, 1995), than did children with fragile X syndrome who did not have autism.

Although individuals with autism only (who do not have fragile X syndrome) can have receptive and expressive vocabulary difficulties, these difficulties vary greatly, depending on an individual's overall cognitive and developmental functioning (e.g., individuals with high functioning autism have less severe language deficits) (L. Dunn, Gomes, & Sebastian, 1996; Joseph, Tager-Flusberg, & Lord, 2002; Kjelgaard & Tager-Flusberg, 2001; Pry, Petersen, & Baghdadli, 2005; Tager-Flusberg, 2004). Speech is generally not affected for those children with autism who use verbal language (Bartolucci & Pierce, 1977; Kjelgaard & Tager-Flusberg, 2001; Rice et al., 2005). Nonetheless, decreased speech intelligibility has been reported in individuals with fragile X syndrome (Abbeduto & Chapman, 2005; Abbeduto & Hagerman, 1997; Madison et al., 1986; Paul et al., 1984; Rice et al., 2005). It is possible that the co-morbidity of autism and fragile X syndrome might lead to more serious speech impairments than are seen in either fragile X syndrome or autism alone, similar to the way that co-morbid autism and fragile X syndrome result in greater cognitive impairments than are seen in fragile X syndrome alone (Philofsky et al., 2004). Because one of our objectives was to examine whether autism status differentially affects vocabulary and speech characteristics of boys with fragile X syndrome, we included groups of boys with fragile X syndrome with and without autism spectrum disorder.

Down syndrome, a genetic disorder in which there is a third chromosome 21, occurs in 1 of every 920 births (Carothers, Hecht, & Hook, 1999; Centers for Disease Control, 1994). Language and speech difficulties occur in individuals who have Down syndrome, with expressive language skills being more impaired than receptive language skills (Abbeduto et al., 2001; Chapman, Seung, Schwartz, & Kay-Raining Bird, 1998; Sigman & Ruskin, 1999). More specifically, these individuals present considerable difficulties with syntax (Abbeduto et al., 2003; Chapman et al., 1998; Eadie, Fey, Douglas, & Parsons, 2002; Fowler, Gelman, & Gleitman, 1994; Scarborough, Rescorla, Tager-Flusberg, Fowler, & Sudhalter, 1991) and speech (Dodd, 1976; Roberts et al., 2005; Smith & Stoel-Gammon, 1983).

The receptive vocabulary level of individuals with Down syndrome has been reported to be generally similar to typically developing children matched for nonverbal cognitive skills, whereas results of studies of expressive vocabulary and speech production have been somewhat inconsistent. The results for expressive vocabulary suggest that findings may vary depending on an individual's age and the nature of the task. Receptive vocabulary did not differ from that of typically developing MA-matched children, adolescents, and young adults on the Test of Auditory Comprehension of Language-Revised (Carrow-Woolfolk, 1985), in a study by Abbeduto et al. (2003), on the Peabody Picture Vocabulary Test–Revised—PPVT-R (M. Dunn, Dunn, & Dunn, 1997), in a study by Chapman, Schwartz, and Kay-Raining Bird (1991), and on the British Picture Vocabulary Scales, Second Edition (L. Dunn, Dunn, Whetton, & Burley, 1997), in a study by Laws and Bishop (2003).

On expressive vocabulary, Laws and Bishop (2003) reported that older children and adolescents with Down syndrome did not differ from nonverbal MA-matched controls on the Expressive Vocabulary subtest of the Kaufman Assessment Battery for Children (Kaufman & Kaufman, 1983). In a more demanding expressive vocabulary task, Chapman and colleagues (1998) found that children and adolescents with Down syndrome produced fewer total and different words in conversational and narrative language samples than did typically developing nonverbal MA-matched children. Other researchers reported that expressive vocabulary in language samples of preschoolers with Down syndrome was delayed relative to nonverbal cognitive level (Miller, 1988), whereas adolescents and young adults with Down syndrome had higher levels of expressive vocabulary on the British Picture Vocabulary Scale-II than nonverbal cognitive skills (Glenn & Cunningham, 2005). Researchers have reported that school-age children with Down syndrome produced more sound errors than did typically developing MA-matched younger children (Dodd, 1976; Roberts et al., 2005; Rosin, Swift, Bless, and Vetter (1988) or typically developing younger children (Smith & Stoel-Gammon, 1983). The inconsistency of these findings for receptive and expressive vocabulary may be due to how the comparison groups were constructed (e.g., nonverbal MA matches, language MA matches), varying severity levels in the Down syndrome groups, CAs of the children with Down syndrome, or possibly family (e.g., maternal education, social capital) or intervention factors. Nonetheless, the mixed findings in this literature certainly require more focused examination.

Boys with Down syndrome provide a good comparison group for examining language and speech development among boys with fragile X syndrome because both groups have similar cognitive impairments and some similar language impairments. Including boys with Down syndrome as a comparison group helps to discern whether the speech and language patterns observed in boys with fragile X syndrome are due to the syndrome in particular rather than to the general effects of mental retardation. This is a first step towards determining the syndrome-specific features of the speech-language profile of fragile X syndrome. In addition, the relationship between vocabulary and MA in Down syndrome needs to be clarified.

Our purpose in the present study was to compare whether boys with fragile X syndrome with and without characteristics of autism spectrum disorder, boys with Down syndrome, and typically developing boys showed similar patterns of receptive vocabulary, expressive vocabulary, and speech acquisition across varying levels of nonverbal ability. We hypothesized that when compared at similar nonverbal cognitive levels, the boys with fragile X syndrome without autism spectrum disorder (fragile X syndrome only) would have stronger vocabulary and speech skills than would the boys with fragile X syndrome– autism spectrum disorder, stronger vocabulary and speech skills than the boys with Down syndrome, and vocabulary levels similar to the typically developing boys. Based on the findings of previous researchers of individuals with fragile X syndrome and Down syndrome (Abbeduto et al., 2003; Chapman et al., 1991), we hypothesized that nonverbal cognitive development would be associated with vocabulary and speech development for all groups. This is consistent with social-interactionist (Bates & MacWhinney, 1982; Craig, 1995; McTear & Conti-Ramsden, 1992) and connectionist and emergentist (Elman, 2001; Elman et al., 1999) perspectives, in which domain-general processes drive learning and there is bi-directional influence of linguistic and nonlinguistic development, rather than perspectives in which language and nonverbal cognitive skills are modular (i.e., unrelated, domain-specific) (Fodor, 1983).

In this study, we conducted repeated assessments of a child's vocabulary and speech skills, so we could examine over time vocabulary and speech skills across varying levels of a child's nonverbal abilities. Because a number of studies have demonstrated that children with higher levels of maternal education have more sophisticated speech and language development (Campbell et al., 2003; Dollaghan et al., 1999; Fewell & Deutscher, 2003; Rice, Spitz, & O'Brien, 1999), in this study we also examined whether maternal education (a proxy for the effects of the environment) influenced the relationship between the boys' vocabulary or speech and their nonverbal cognitive skills.

Method

Study Population

Study participants were boys with fragile X syndrome without characteristics of autism spectrum disorder (fragile X syndrome only) and with characteristics of autism spectrum disorder (fragile X syndrome–autism spectrum disorder), boys with Down syndrome, and typically developing boys. The groups did not differ statistically on nonverbal MA, with mean MAs of 59 months (fragile X syndrome only), 53 months (fragile X syndrome-autism spectrum disorder), 55 months (Down syndrome), and 56 months (typically developing). The boys with fragile X syndrome only, fragile X syndrome–autism spectrum disorder, and Down syndrome did not differ on nonverbal IQ at study entry, with IQs of 59, 58, and 60, respectively. Enrollment criteria for the boys with fragile X syndrome and boys with Down syndrome were an age of less than 16 years, a language level of at least 40 expressive words, and emergent word combinations (mean length of utterance greater than 1.1). The typically developing boys were enrolled between 2 and 6 years of age, such that the distribution of developmental ages for their nonverbal cognitive abilities on the Brief IQ composite of the Leiter International Performance Scale– Revised—Leiter-R (Roid & Miller, 1997) was similar to those of the boys with fragile X syndrome and Down syndrome. The boys with fragile X syndrome were further categorized as having autism/ autism spectrum or without autism, as described below. Details about study recruitment and procedures have been previously reported (see Roberts et al., 2005).

We excluded boys in homes where English was not the primary language spoken and boys whose primary mode of communication was sign language. Boys with fragile X syndrome and Down syndrome whose average hearing threshold was greater than 30 dB HL in the better ear across 500, 1,000, 2,000, and 4,000 Hz were also excluded as were typically developing boys whose hearing thresholds were greater than 25 dB HL. In addition, we excluded boys with Down syndrome who had a previous diagnosis of autism spectrum disorder at study entry, and typically developing boys who had a developmental disability, autism spectrum disorder, hearing loss, speech or language difficulties, or were receiving speech/language therapy at entry.

To determine whether a boy with Down syndrome had received a diagnosis of autism spectrum disorder or a typically developing boy had any of these disabilities or was receiving speech-language therapy, we initially interviewed parents. After study entry, we excluded any child with Down syndrome or typically developing child who scored in the autism range on the Autism Diagnostic Observation Schedule-General (Lord, Rutter, DiLavore, & Risi, 2002) that we administered, as well as any typically developing child who scored more than 1.5 SDs below the mean on any standardized speech or language measure that we administered at the initial assessment.

All of the boys with fragile X syndrome were diagnosed with full mutation, confirmed by DNA analyses. They were recruited from an ongoing longitudinal study of boys with fragile X syndrome or were referred from physicians' offices, genetic clinics, or developmental clinics. The boys lived in North Carolina, South Carolina, Virginia, Maryland, Florida, Delaware, New Jersey, Pennsylvania, Tennessee, and Georgia. The School of Medicine Institutional Review Board at the University of North Carolina at Chapel Hill annually reviewed and approved the study protocols. The child's parent or guardian provided informed consent at entry into the study.

Fragile X syndrome without autism spectrum disorder (fragile X syndrome-only)

Thirty-three boys with fragile X syndrome only, who were between 2.9 and 14.4 years of age (M = 9.5) at the initial assessment, participated in the study. Their mean age equivalent score on the Brief IQ composite of the Leiter-R was 5.0 years. With regard to ethnicity, 79% of the boys were Caucasian, 15% were African American, and 6% were other. Maternal education ranged from 12 to 20 years (M = 14.1). One additional boy with fragile X syndrome was excluded from the study due to sensorineural hearing loss.

Fragile X syndrome with autism spectrum disorder

Forty-nine boys with fragile X syndrome and characteristics of autism spectrum disorder, who were between the ages of 3.5 and 14.0 years (M = 8.3) at the first assessment participated. Their mean age equivalent score on the Brief IQ composite of the Leiter-R was 4.4 years. With regard to ethnicity, 92% of the boys were Caucasian, 6% were African American, and 2% were other. Maternal education ranged from 12 to 20 years (M = 14.9).

Down syndrome

There were 39 boys with Down syndrome between 4.3 and 15.9 years of age (M = 8.4) at the first assessment. Parents reported that the source of the Down syndrome was Trisomy 21 for 38 of the boys and translocation for 1 boy. The mean age equivalent score on the Leiter-R Brief IQ composite was 4.6 years. The boys with Down syndrome were recruited from physicians' offices, schools, genetic clinics, and developmental clinics in North Carolina, South Carolina, and Virginia. Their ethnicity was 90% Caucasian, 8% African American, and 2% other. Mothers' educational levels ranged from 7 to 20 years (M = 15.6). Two additional boys with Down syndrome were not included in this study because they received a diagnosis of autism after entering the study, and 3 more boys with Down syndrome were excluded because they scored in the autism spectrum disorder range on the Autism Diagnostic Observation Schedule-General that we administered.

Typically developing

There were 41 typically developing boys participating whose distribution of scores on the Leiter-R Brief IQ was similar to the boys with fragile X syndrome. The typically developing boys were between 2.1 and 6.6 years of age (M = 4.4) at study entry, with a mean score on the Leiter-R Brief IQ composite of 4.7 years. The typically developing boys were recruited from physicians' offices, childcare centers, and schools in North Carolina. Of these participants, 71% were Caucasian, 17% African American, and 12% other. Mothers' education levels ranged from 12 to 20 years (M = 16.4). Three additional typically developing boys were excluded from the study because of sensorineural hearing loss, a low score of more than 1.5 SDs below the mean on the Goldman Fristoe Test of Articulation-2, or were receiving speech and language therapy.

Assessments

Receptive vocabulary

The PPVT-III was used to measure receptive vocabulary. The individual was asked to select the visual representation of a word provided by the examiner from among four choices. An age equivalent score for each child's performance was calculated.

Expressive vocabulary

Expressive vocabulary was assessed with the Expressive Vocabulary Test (Williams, 1997). In this test, the individual is asked to label a picture or give a synonym for the word provided by the examiner that also labels the picture. An age equivalent for each child's performance was computed.

Speech production

The Sounds-in-Words subtest of the Goldman-Fristoe Test of Articulation-2 (Goldman & Fristoe, 2000) was used to assess speech production at the single-word level. This test, which was designed to elicit single-word responses to stimulus pictures, measures the ability to produce all of the English consonants in the initial, medial, and final position in common words. An age equivalent for each child's performance was computed.

Responses to the Goldman Fristoe Test of Articulation-2 were audiotaped using a portable Digital Auditory Tape TASCAM (DA-P1) recorder with a Shure WBH 53 microphone system and videotaped using a Sony (DCR-TVR27) Digital 8 Camcorder. The boys' speech was transcribed by two trained speech-language pathologists who used narrow transcription guidelines, as described in Shriberg and Kent (2003). In addition to substitution and omission errors, errors on dentalization, lateralization, frictionalization, derhoticization, and nasalization/nasal emission were counted as incorrect on this test. Interobserver agreement was coded on 16% of the speech samples distributed across the three groups (23 boys with fragile X syndrome, 13 boys with Down syndrome, and 17 typically developing boys). Point-by-point comparison of phonological units was made so that all cluster elements had to be the same for an agreement to be counted. The average percentage agreement between two transcribers for broad transcription was 91.4% and ranged from 76.9% to 100.0% (Ms of 90.4% for fragile X syndrome, 89.0% for Down syndrome, and 94.5% for typically developing). For narrow transcription, the average percentage agreement between two transcribers was 88.8% and ranged from 70.8% to 100.0% (Ms of 88.0% for fragile X syndrome, 85.1% for Down syndrome, and 92.6% for typically developing). For these analyses, we included only boys who had attempted at least 72 of the 77 consonant phonemes and consonant blends targeted on the Goldman Fristoe Test of Articulation-2. That is, the boys could be missing words as long as the total number of target consonants contained in those missing words was 5 or less.

Nonverbal cognition

The Leiter-R was used to assess nonverbal cognition. The individual is asked to find an item in a picture, choose the next item in a sequence, or arrange items in a pattern. Four subtests that comprise the Brief IQ composite were administered: Figure Ground, Form Completion, Sequential Order, and Repeated Patterns. The Leiter-R was standardized on 1,719 individuals 2 to 20 years of age. An age equivalent and the Brief IQ composite were computed for each child.

Autism spectrum disorder

The boys with fragile X syndrome were classified as autistic, autism spectrum, or not autistic using the Autism Diagnostic Observation Schedule-General (Lord et al., 2002). This assessment is a standardized observation of children's communicative and social behavior that discriminates autism spectrum disorder from other developmental disorders as well as from normal behavior. The examiner interacts with the child for approximately 45 minutes in a series of structured and semi-structured activities in which the child is given opportunities to exhibit behaviors indicative of autism/pervasive developmental disorder. Trained examiners scored the tapes; reliability computed on 16% of the boys was .89 for the individual items (range = .83 to .96) and .93 on autism diagnosis (range = .81 to 1.00). A total of 19 boys with fragile X syndrome were classified as having autism, 30 as having autism spectrum, and 33 boys as not having autism. In this analysis, the boys in the autism and autism spectrum groups were combined into one group labeled “autism spectrum disorder.” The Autism Diagnostic Observation Schedule-General was also administered to the boys with Down syndrome and typically developing boys in order to exclude any boys from the data analysis that scored in the autism spectrum disorder range.

Analysis Strategy

We conducted a repeated measures analysis using general linear mixed models in SAS Proc Mixed to compare development of speech and language skills for the four groups of boys: boys with fragile X syndrome only, boys with fragile X syndrome–autism spectrum disorder, boys with Down syndrome, and typically developing boys. At study entry, boys in the four groups did not differ statistically on Leiter nonverbal MA on the Leiter Brief IQ using an analysis of variance (ANOVA), F(3, 158) = 1.87, p = .138 (see Table 1 for the mean scores). Further, the boys with fragile X syndrome with and without autism and the boys with Down syndrome did not differ on nonverbal IQ at study entry, F(2, 118) = .15, p = .86. We used three separate two-level analyses to examine the longitudinal assessments of receptive vocabulary (PPVT-III), Expressive Vocabulary Test, and speech acquisition (Goldman Fristoe Test of Articulation-2). These analysis models were used to estimate a separate variance and covariance term for each repeated measure for each of the four groups. Up to four repeated assessments had been collected per each study participant, and the general linear mixed models allowed us to include as many assessments as possible through fitting models similar to hierarchical linear models (Singer & Willet, 2003). Furthermore, longitudinal assessments of nonverbal cognitive skills (Leiter-R) were also collected. The nonverbal cognitive level, rather than CA, was included as the time predictor because nonverbal cognitive level should provide better and more comparable prediction across the four analysis groups. Its use should account for differences among the groups in nonverbal cognitive skills, thereby allowing us to test whether the four groups differed in terms of language and speech development after controlling for substantial group differences in overall nonverbal cognitive skills. This approach increased power to detect differences compared with a cross-sectional analysis because precision was increased through including repeated assessments and allowing for likely group differences in covariance structures.

Table 1.

Means and SDs for Vocabulary and Speech Age Equivalent Scores (in Months and Background Variables)

Means and SDs for Vocabulary and Speech Age Equivalent Scores (in Months and Background Variables)
Means and SDs for Vocabulary and Speech Age Equivalent Scores (in Months and Background Variables)

The two-level repeated measures analysis involved one level that described the longitudinal patterns within boys and another level that identified group differences in those longitudinal patterns. The first level described patterns of change in the vocabulary and speech outcomes as a function of changes in nonverbal cognitive skills. The second level was used to test whether either individual differences in level (i.e., intercept) or change with respect to nonverbal cognitive skills (i.e., slope) varied as a function of group and maternal education. At this level, intercepts and slopes for each of the four groups were estimated and compared. Maternal education was measured by total years of the mothers' education at time of enrollment in the study.

Therefore, the three separate analysis models consisted of three main fixed effects (syndrome group, nonverbal MA, and maternal education) and the interaction between syndrome group and nonverbal MA (i.e., Group × Developmental Age) to test whether syndrome moderated the relationship between the boys' vocabulary or speech skills and their nonverbal cognitive skills. We centered the data at the mean nonverbal cognitive level across the four groups, which was approximately 60 months. As a precaution against making Type I errors, we adjusted the p-value for all follow-up contrasts (6 pairwise comparisons) using the LSD method. Any comparison between two groups was considered statistically different when p was less than .008 (i.e., .05/6 = .008). Effect sizes for significant differences between group means were computed as the difference between the adjusted means for the two groups divided by the SD for the typically developing boys. Effect sizes for significant differences between groups in terms of the slope for nonverbal cognitive level were computed as the difference between slopes for the two groups times the SD for nonverbal development age for the typical group and divided by the SD on the outcome for the typical group.

Results

Variability Among Children

Table 1 provides descriptive information about receptive vocabulary, expressive vocabulary, and speech production for each assessment visit across the four groups (boys with fragile X syndrome only, boys with fragile X syndrome–autism spectrum disorder, boys with Down syndrome, and typically developing boys). The boys with fragile X syndrome and boys with Down syndrome showed marked delays in their vocabulary and speech compared to expected norms. All groups showed considerable individual variability. The mean age equivalent scores at each visit shows that the boys were generally increasing in their language and speech over time. However, comparisons within measures are difficult because the number of children listed in Table 1 varied by the assessment visit. The correlations among each of the speech and vocabulary measures across the three of four assessment time points were very high for the typically developing boys (median range of r = .79 to .87), fragile X syndrome only (median range of r = .87 to 93), fragile X syndrome–autism spectrum disorder (median range of r = .90 to .97), and Down syndrome (median range of r = .70 to 81) groups. The developmental age scores on the PPVT-III, Expressive Vocabulary Test, and Goldman Fristoe Test of Articulation-2 were moderately to highly correlated at the first assessment for typically developing (median r = .40), fragile X syndrome only (median r = .56), fragile X syndrome–autism spectrum disorder (median r = .60), and Down syndrome (median r = .60) groups as well as at subsequent assessment visits. Developmental ages on the language and speech measures at each assessment were also moderately to highly correlated with nonverbal cognitive level on the Leiter-R for the typically developing (r = .76 for PPVT-III; .85, Expressive Vocabulary Test; and .43, Goldman Fristoe Test of Articulation-2); fragile X syndrome only (r = .43 for PPVT-III; .56, Expressive Vocabulary Test; and .56, Goldman Fristoe Test of Articulation-2); fragile X syndrome–autism spectrum disorder (r = .65 for PPVT-III; .66, Expressive Vocabulary Test; and .55, Goldman Fristoe Test of Articulation-2); and Down syndrome (r = .87 PPVT-III; .81, Expressive Vocabulary Test; and .53, Goldman Fristoe Test of Articulation-2) groups.

Vocabulary and Speech Analyses

Table 2 lists the adjusted means, estimated slopes for nonverbal cognitive level, standard errors, and omnibus F tests for the analysis of receptive vocabulary, expressive vocabulary, and speech production. The first five rows of Table 2, designated by the heading Group, show the average nonverbal cognitive level for receptive and expressive vocabulary and speech skills at the sample mean at the Leiter-R nonverbal cognitive level of 60 months for each group of boys (i.e., adjusted means and standard errors). Letter superscripts are used to identify differences in adjusted means that were not statistically significant at a .008 level (after LSD adjustment). The F test for the interaction can be found in the row designated by the heading Group × Nonverbal MA. The following four rows show the average rate of change in the nonverbal cognitive level for vocabulary/speech skills for a one-month increase in Leiter-R nonverbal cognitive level for each group of boys (i.e., the regression coefficient, B, and standard error). The last row in Table 2, labeled Covariate, contains the regression coefficient of Leiter-R nonverbal cognitive level and maternal education. The reported means for receptive and expressive vocabulary and speech production were adjusted for maternal education.

Table 2.

Multilevel Model Results: Predicting Receptive Vocabulary, Expressive Vocabulary, and Speech Production Developmental Age (DA) Across Nonverbal MA

Multilevel Model Results: Predicting Receptive Vocabulary, Expressive Vocabulary, and Speech Production Developmental Age (DA) Across Nonverbal MA
Multilevel Model Results: Predicting Receptive Vocabulary, Expressive Vocabulary, and Speech Production Developmental Age (DA) Across Nonverbal MA

Receptive vocabulary

The groups differed significantly in their receptive vocabulary level on the PPVT-III when compared at a similar nonverbal cognitive level (i.e., mean nonverbal MA), and no evidence emerged suggesting that the four groups differed in their association between receptive language and nonverbal cognitive level. As shown in Table 2, the adjusted means of receptive vocabulary developmental age mean for the boys with Down syndrome was significantly lower than those of the typically developing boys and boys with fragile X syndrome only when compared at the mean nonverbal cognitive level. However, receptive vocabulary for the boys with Down syndrome did not differ from the fragile X syndrome–autism spectrum disorder group, nor did the typically developing boys and the two fragile X syndrome groups differ. Large statistically significant effect sizes characterized differences between boys with Down syndrome and both the boys with fragile X syndrome, d = −.61, and the typically developing boys, d = −.63, whereas moderate, nonsignificant differences emerged in the comparisons of the boys with fragile X syndrome–autism spectrum disorder and boys with fragile X syndrome only, d = −.39, typically developing boys, d = −.37, and boys with Down syndrome, d = .25. As expected, maternal education was a significant control variable in this analysis of receptive vocabulary.

Expressive vocabulary

The groups differed significantly in both their expressive vocabulary level when compared at a similar level of nonverbal cognitive skills and in the association between expressive language and nonverbal MA. Maternal education was a statistically significant control for expressive vocabulary. Table 2 lists the coefficients from the analysis, and Figure 1 shows the estimated regression lines for the four groups. At the mean developmental age of close to 60 months, the boys with fragile X syndrome–autism spectrum disorder and the boys with Down syndrome scored significantly lower than did the typically developing boys. The boys with fragile X syndrome only did not differ reliably from the other three groups, .16 < d < .30

Figure 1.

Predicted trajectories for Expressive Vocabulary (EVT) Developmental Age (DA) by Leiter-R nonverbal MA for typically developing boys (TD), boys with Down syndrome (DS), fragile X syndrome only (FXS only), and fragile X syndrome with autism spectrum disorders (ASD)

Figure 1.

Predicted trajectories for Expressive Vocabulary (EVT) Developmental Age (DA) by Leiter-R nonverbal MA for typically developing boys (TD), boys with Down syndrome (DS), fragile X syndrome only (FXS only), and fragile X syndrome with autism spectrum disorders (ASD)

In addition, the analysis indicated that the association between expressive vocabulary and nonverbal cognitive level differed among the four groups. The estimated slopes for each of the four groups is shown in Table 2. Comparisons of these slopes suggest that boys with Down syndrome differed in their rate of change of expressive vocabulary acquisition relative to their nonverbal cognitive level as compared to the boys with fragile X syndrome–autism spectrum disorder, d = .29. The association between expressive vocabulary developmental age and nonverbal cognitive development age did not differ among the other group comparisons. To further interpret this interaction for the Down syndrome as compared to the fragile X syndrome–autism spectrum disorder group, as shown in Figure 1, we estimated Expressive Vocabulary Test at lower and higher Leiter-R nonverbal cognitive levels. For example, at the 25th percentile of nonverbal cognitive age (45 months), the boys with Down syndrome were estimated to have an age equivalent expressive vocabulary average of 45 months, whereas the fragile X syndrome–autism spectrum disorder group had a slightly higher score (46.7 months). However, at the 75th percentile of nonverbal cognitive age (67 months), although the age equivalent expressive vocabulary scores for both Down syndrome and fragile X syndrome–autism spectrum disorder groups were lower than their nonverbal cognitive age, the expressive vocabulary age of the Down syndrome group (59.7 months) was higher than that of the fragile X syndrome–autism spectrum disorder group (56 months). That is, the boys with Down syndrome tended to have lower developmental ages for expressive vocabulary across the younger Leiter-R nonverbal cognitive levels, but changed so that their average expressive vocabulary developmental ages were more comparable to the nonverbal Leiter-R cognitive levels at the older Leiter-R nonverbal cognitive levels included in this study.

Speech production

The groups differed significantly in their level of speech production on the Goldman Fristoe Test of Articulation-2 with respect to the boys' nonverbal cognitive level, whereas their rate of change for speech production did not significantly differ between the groups. As shown in Table 2, the adjusted means of developmental age of speech production were much less for the boys with Down syndrome than for both fragile X groups and the typically developing group. The boys with Down syndrome scored substantially lower than did typically developing boys, d = .89, boys with fragile X syndrome only, d = 1.39, and boys with fragile X syndrome and autism, d = 1.21. Maternal education was not a significant control for speech production.

Discussion

Our purpose in the present study was to compare the vocabulary and speech development of boys with fragile X syndrome with and without characteristics of autism spectrum disorder to that of boys with Down syndrome and typically developing boys. We hypothesized that after adjusting for nonverbal cognitive age, the boys with fragile X syndrome-only would not differ in their receptive or expressive vocabulary or speech skills from the typically developing boys. This hypothesis was confirmed. Our findings are similar to previous studies of primarily adolescents and adults and a few children in which researchers found receptive vocabulary on the Test of Auditory Comprehension of Language-Revised (Abbeduto et al., 2003) and speech production in single-words utterances on a standardized articulation test (Hanson, Jackson, & Hagerman, 1986; Palmer et al., 1988; Prouty et al., 1988; Roberts et al., 2005) were similar to those of typically developing younger individuals. However, these findings differed from Sudhalter et al. (1992), who found that boys and adult males with fragile X syndrome had more semantically incorrect words on a nonstandardized sentence completion test than did typically developing individuals of the same MA. It is difficult to compare these findings because the sentence completion task used by Sudhalter and colleagues to measure expressive vocabulary may place more cognitive and linguistic demands on a child than did the receptive vocabulary measures used in our study as well as the study by Abbeduto and colleagues (2003).

We also hypothesized that the presence of characteristics of autism spectrum disorder among the boys with fragile X syndrome would affect their receptive and expressive vocabulary and their speech development. We found a mixed pattern of results for the boys with fragile X syndrome– autism spectrum disorder. The boys with both disorders scored lower in expressive vocabulary than the typically developing group, but the two groups did not differ in receptive vocabulary or speech production. Further, the comparisons of the boys with and without autism spectrum disorder did not differ on any of the vocabulary or speech measures. It is important to note that the limited power due to sample size is the most likely explanation for why we did not see differences between the two fragile X syndrome groups and between the typically developing and fragile X syndrome–autism spectrum disorder groups in receptive vocabulary. Our sample size is very good compared to previous studies in fragile X syndrome, but we have limited ability to detect modest or moderate differences. Results further suggest that boys with fragile X syndrome–autism spectrum disorder had lower expressive vocabulary levels relative to their nonverbal cognitive level.

We also sought to determine whether communication skills are less impaired among boys with fragile X than among boys with Down syndrome, a developmental disorder with similar cognitive delays. Compared to the boys with fragile X without autistic disorder, we hypothesized that the boys with Down syndrome would have lower receptive and expressive vocabulary and speech skills. This hypothesis was confirmed for receptive vocabulary and speech production, which suggests that delay in receptive vocabulary and speech production at the single-word level (relative to MA) may differentiate the communication profiles of the two syndromes, while both syndromes shared similar levels of expressive vocabulary. Thus, these findings begin to elucidate some common features of the language and speech phenotype that the two syndromes share as well as some differences.

In this study, the boys with Down syndrome had lower receptive vocabulary, expressive vocabulary, and speech production than did the typically developing boys after adjusting for nonverbal cognitive skills. Our study results for receptive vocabulary are not consistent with three previous studies in which children, adolescents, and adults with Down syndrome had receptive vocabulary levels similar to those of typically developing children matched for nonverbal skills on such standardized tests as the Test of Auditory Comprehension of Language-Revised (Abbeduto et al., 2003), PPVT-R (Chapman et al., 1991), and the British Picture Vocabulary Test-II (Laws & Bishop, 2003). Although it is not clear why our study results differed from previous studies, our participants with Down syndrome were generally younger than those in the previous studies, thus implicating a slower acquisition of such skills at the young age levels. However, our expressive vocabulary findings are consistent with one study, in which Chapman et al. (1998) found that children and adolescents with Down syndrome had more limited vocabulary on language samples than did MA-matched children. The findings in this study for speech are similar to those of previous studies of school-age children with Down syndrome who had more delayed speech than typical MA-matched children (Dodd, 1976; Roberts et al., 2005; Rocin et al., 1988) and typical younger children (Smith & Stoel-Gammon, 1983).

In addition, we found that the boys with Down syndrome showed a stronger positive association between their expressive vocabulary age and nonverbal cognitive age than did the boys with fragile X syndrome–autism spectrum disorder, suggesting that the Down syndrome group differed in their pattern of expressive vocabulary acquisition at younger versus older nonverbal MAs. That is, the boys with Down syndrome tended to have lower expressive vocabulary developmental ages across younger nonverbal cognitive ages, but acquired expressive vocabulary more rapidly, such that their average expressive vocabulary developmental ages are more comparable to their nonverbal MAs at the oldest nonverbal cognitive levels studied. We did not find this association for receptive vocabulary or speech. It is not clear why we found greater gains in expressive vocabulary for the boys with Down syndrome relative to their MA. Possibly, consistent with social–interactionist perspectives, older children with Down syndrome who are socially oriented and seek interactions with other people take more advantage of their world experiences, which enrich their word knowledge. Further, cognitive processes affecting expressive vocabulary may be less affected in boys with Down syndrome than in boys with fragile X syndrome and may be more evident in older children.

We also found that maternal education was a significant control variable for receptive and expressive vocabulary, but not for speech production. We chose to statistically control for maternal education as a proxy for the effects of environmental factors, such as interaction style and stimulation and responsiveness of the home environment, on the relationship between children's verbal and nonverbal skills. Our findings are consistent with previous researchers who found that children with mothers of higher levels of education have more sophisticated language development (Dollaghan et al., 1999; Fewell & Deutscher, 2003; Rice et al., 1999). Although unlike Campbell and colleagues (2003), we failed to find such a relationship for maternal education and speech development. However, our findings were congruent with Dollaghan and colleagues (1999), suggesting that perhaps the failure to find a significant relationship for speech production indicates that speech production, as compared to vocabulary, is more of a motor behavior and may evolve via a different developmental cadence than do language functions and may not be as amenable to parent interaction variables related to education level.

There are several strengths of this study. First, compared to previous studies, there was a relatively large sample of boys with fragile X syndrome and Down syndrome participating. However, as cautioned earlier, we had limited ability to detect modest or moderate group differences. Second, the boys with fragile X syndrome were compared to a syndrome comparison group of boys with Down syndrome, with similar nonverbal MAs, so that we could understand the similarities and differences in these syndromes. Comparing the fragile X syndrome profile to the Down syndrome profile is not sufficient to identify language and speech characteristics in fragile X syndrome as syndrome specific; that is, the profile may be shared by many other syndromes not examined here. However, these comparisons are a first step toward establishing syndrome specificity of the profiles in fragile X syndrome. Third, we also compared the syndrome groups to typically developing boys with similar nonverbal MAs so that we could understand whether differences in language and speech characteristics can be explained by general cognitive delay or if there is some different pattern relative to typical development. Fourth, we prospectively documented the boys' vocabulary and speech, having up to four assessments on some of the boys. Fifth, we used well-accepted measures with good psychometric characteristics to assess vocabulary and speech and to classify the boys with fragile X syndrome according to their autism spectrum disorder status. Finally, we controlled for maternal education, a measure of the child's environment that has been shown in previous literature to be an important predictor of children's language and speech development (Campbell et al., 2003; Dollaghan et al., 1999; Fewell & Deutscher, 2003; Rice et al., 1999).

There are also some limitations in this study that are important to consider in relation to future directions for research. First, we used standardized measures of receptive and expressive vocabulary and of speech production at the single-word level. Analyses of both vocabulary and speech at the conversational level may result in different findings and should be included in studies examining the communication development of children with fragile X syndrome and Down syndrome. Second, we looked at global measures of vocabulary and speech. More specific analyses of aspects of vocabulary (e.g., abstract nouns or the organization of semantic categories) or phonology (e.g., cluster reduction or sound omissions) as well as analyses of other areas of language (e.g., syntax or pragmatics) and speech (e.g., intelligibility or rate), may produce different results and aid in our understanding of the communication phenotype of boys with fragile X syndrome and Down syndrome. Third, the number of boys with fragile X syndrome classified with autism spectrum disorder was high (consisted of boys in the autistic disorder and autism spectrum groups) and may reflect an overestimation of autistic tendencies by the Autism Diagnostic Observation Schedule-General due to the social anxiety and hyperarousal common among children with fragile X syndrome. Future researchers should categorize autism using additional measures of autism and separately examine children with autism and autism spectrum disorders. Fourth, we adopted a conservative criterion to exclude children with hearing loss in our study as compared to some previous language studies of individuals with fragile X or Down syndrome (Abbeduto et al., 2003; Boudreau & Chapman, 2000; Chapman et al., 1991). Boys with fragile X syndrome or Down syndrome who had a hearing threshold greater than 30 dB HL average in the better ear across 500, 1,000, 2,000, and 4,000 Hz were excluded from the study. We felt that having a lower minimal threshold was necessary to exclude children who had co-occurring hearing loss and a syndrome that affected their language development. Fifth, our unusual finding that the receptive vocabulary level of children with Down syndrome was lower than that of nonverbal MA matches may indicate that our Down syndrome sample was not representative, possibly limiting the generalizability of our findings. Finally, we examined only one covariate for the boys' vocabulary and speech development: their mothers' highest level of education. The examination of other important covariates, such as a child's working memory and level of FMRP for boys with fragile X syndrome, as well as specific measures of maternal responsiveness, would be important to enhance our understanding of the specific factors that predict vocabulary and speech development in boys with fragile X syndrome and Down syndrome. Also, it would be important to determine whether specific factors are more important at certain points in development. In addition, the education level of the mothers in our study was relatively high and may limit the generalizability of our findings.

These data have several important implications for the assessment and intervention of boys with fragile X syndrome and Down syndrome. First, intervention for boys with fragile X syndrome should be focused less on speech production at the isolated word level and more on increasing vocabulary skills, particularly expressive vocabulary skills. Intervention for boys with Down syndrome should be focused on increasing speech accuracy at the single-word level as well as receptive and expressive vocabulary development. Second, autism spectrum disorder in a child with fragile X syndrome should be determined and findings considered in intervention planning strategies, given that we found some support for the potential impact of the co-occurrence of fragile X syndrome–autism spectrum disorder on receptive and expressive vocabulary skills. Third, the finding that maternal education is a significant control variable for receptive and expressive vocabulary highlights the importance of a child's environment on their vocabulary development and an array of variables that interventionists can target for change. Fourth, given the individual variability in speech and vocabulary development among boys with fragile X syndrome as well as boys with Down syndrome, each child's intervention plan should build on his particular strengths in language and speech and target areas of weakness.

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This research was supported by the National Institute of Child Health and Human Development Grants 1 R01 HD38819, 1 R01 HD044935, and 1 R03 HD40640. We thank the children and families who participated in this study. We greatly appreciate the assistance of Anne Harris, Siara Cowan, Cassia Gerolimatos, Julia Jurgens, and Kathleen Neff for their assistance with data collection. We also appreciate the assistance of Robin Chapman, Helen Tager-Flusberg, Stephen Long, Lawrence Shriberg, and Raymond Kent on our protocol development. We thank the staff of the Carolina Fragile X Project, directed by Donald Bailey, for assistance on this project. We appreciate Sarah Henderson's assistance in manuscript preparation. The first author is also affiliated with Division of Speech and Hearing Sciences and Department of Pediatrics, University of North Carolina at Chapel Hill, and the final author is also affiliated with the Department of Psychiatry and The Clinical Center for the Study of Development and Learning, University of North Carolina at Chapel Hill. Requests for reprints should be sent to Joanne E. Roberts, FPG Child Development Institute, University of North Carolina at Chapel Hill, 105 Smith Level Road, CB# 8180, Chapel Hill, NC 27599-8180. joanne_roberts@unc.edu