Speech, Language and Non-verbal Communication in CLN2 and CLN3 Batten Disease

Abstract

CLN2 and CLN3 diseases, the most common types of Batten disease (also known as neuronal ceroid lipofuscinosis), are childhood dementias associated with progressive loss of speech, language and feeding skills. Here we delineate speech, language, non-verbal communication and feeding phenotypes in 33 individuals (19 females) with a median age of 9.5 years (range 3-28 years); 16 had CLN2 and 17 CLN3 disease; 8/15 (53%) participants with CLN2 and 8/17 (47%) participants with CLN3 disease had speech and language impairments prior to genetic diagnosis. At the time of study all participants, bar one, had language impairments. The remaining participant with typical language was tested at age 3 years, following pre-symptomatic enzyme replacement therapy (ERT) from age 9 months. CLN2 and CLN3 disease had different profiles. For CLN2 disease, all affected individuals showed language impairment with dysarthria; older individuals with classical disease progressively became non-verbal. For CLN3 disease, the presentation was more heterogeneous. Speech impairment was evident early in the disease course, with dysarthria (13/15, 87%), often manifesting as neurogenic stuttering (5/15, 33%). Participants with CLN2 disease had comparable expressive and receptive language skills (p > 0.99), yet participants with CLN3 disease had stronger expressive language than receptive language skills (p = 0.004). Speech, cognitive and language impairment and adaptive behaviour showed progressive decline in both diseases. Individuals with pre-symptomatic ERT or atypical CLN2 disease were less impaired. Challenging behaviours were common in CLN3 (11/17, 65%), but less frequent in CLN2 (4/16, 25%) disease. Individuals with Batten disease require tailored speech therapy incorporating communication partner training utilising environment adaptations and informal communication behaviours.

Keywords: Batten disease; CLN2; CLN3; cerliponase alfa; enzyme replacement therapy; language; neuronal ceroid lipofuscinoses; speech.

FIGURE 1

Phenotypes of participants with classical CLN2, CLN3 and atypical CLN2 disease. Circles represent individuals; grey circles = feature absent and black circles = feature present. AAC = augmentative and alternative communication system, Age ERT = average age starting ERT, Impaired adaptive behaviour = Vineland‐3 adaptive behaviour composite score < 85, Ax = assessed for this study, Dx = diagnosed, ERT = enzyme replacement therapy, Impaired language = Vineland‐3 communication domain score < 85, mo = months, N = number, NA = not applicable, yrs = years.

FIGURE 2

Roadmap of Communicative Competence. Roadmap of Communicative Competence (ROCC) scores across 10 communicative competencies in participants with CLN2 (n = 14) and CLN3 (n = 16) disease ordered from oldest to youngest (left to right). In CLN2 disease, two participants highlighted in yellow are atypical cases, and the two participants highlighted in green are classical cases who had ERT pre‐symptomatically. Emergent, transitional and independent communication defined by the ROCC; Emergent communicators typically use behaviours, gestures, facial expressions and body language and often require a familiar person to interpret their communication; Transitional communicators have some symbolic communication and communicate best with familiar people; Independent communicators can communicate autonomously with unfamiliar people.

FIGURE 3

Perceptual speech features in participants with CLN2 (n = 8) and CLN3 disease (n = 15). Dysarthria symptoms assessed using the Mayo Clinic Dysarthria Rating System [45], and articulation and phonological impairments assessed using Dodd's [14] system for speech disorder differential diagnosis.

FIGURE 4

(a) Vineland‐3 score communication domain and age in participants with classical CLN2 disease and CLN3 disease. Communication domain scores on the Vineland Adaptive Behaviour Scales 3rd Edition (Vineland‐3) (normative mean = 100, normative SD = 15). Participants with classical CLN2 disease (yellow): n = 12, r = −0.87, 95% CI = −0.96 to −0.60, R ² = 0.77, p = 0.0002. Participants with CLN3 disease (red): n = 17, r = −0.76, 95% CI = −0.91 to −0.43, R ² = 0.57, p = 0.0005. (b) Vineland‐3 score adaptive behaviour composite and age in classical CLN2 disease and CLN3 disease. Adaptive Behaviour Composite scores on the Vineland Adaptive Behaviour Scales 3rd Edition (Vineland‐3) (normative mean = 100, normative SD = 15). Participants with classical CLN2 disease (yellow): n = 12, r = −0.85, 95% CI = −0.96 to −0.55, R ² = 0.73, p = 0.0004. Participants with CLN3 disease (red): n = 17, r = −0.78, 95% CI = −0.92 to −0.47, R ² = 0.60, p = 0.0002.

FIGURE 5

(a) CCC‐2 subdomains in participants with classical CLN2 disease. Children's Communication Checklist 2nd Edition (CCC‐2) scores in participants with classical CLN2 disease (n = 4) subdomain scores (normative mean = 10, SD = 3): Speech (mean = 3, SD = 3.17), Syntax (mean = 2, SD = 3.37), Semantic (mean = 6.80, SD = 2.22), Coherence (mean = 5.50, SD = 1.92), Inappropriate initiation (mean = 8.75, SD = 2.87), Stereotyped (mean = 6.50, SD = 1.73), Use of context (mean = 5.25, SD = 2.99), Non‐verbal (mean = 7.50, SD = 4.20), Social (mean = 4.75, SD = 4.19) and Interests (mean = 7.50, SD = 2.38). Differences between subdomains: χ ² = 21.66, p = 0.01. Middle line = median, bottom whisker = minimum, upper whisker = maximum. (b) CCC‐2 subdomains in participants with CLN3 disease. Children's Communication Checklist 2nd Edition (CCC‐2) scores in participants with CLN3 disease (n = 15) subdomain scores (normative mean = 10, SD = 3): Speech (mean = 4.93, SD = 4.18), Syntax (mean = 5.27, SD = 3.83), Semantic (mean = 3.53, SD = 3.07), Coherence (mean = 4.93, SD = 3.13), Inappropriate initiation (mean = 4.67, SD = 2.53), Stereotyped (mean = 6.20, SD = 3.41), Use of context (mean = 3.27, SD = 2.15), Non‐verbal (mean = 4.13, SD = 2.39), Social (mean = 3.27, SD = 2.82) and Interests (mean = 5.07, SD = 1.16). Differences between subdomains: χ ² = 28.86, p = 0.0007. Middle line = median, bottom whisker = minimum, upper whisker = maximum.

FIGURE 6

Communication Matrix scores. Communication Matrix scores across communicative functions in participants with classical CLN2 (n = 9) and CLN3 (n = 2) disease who do not use connected speech to communicate ordered from oldest to youngest (left to right). Level 0 = does not display, Level 1 = pre‐intentional behaviour, Level 2 = intentional behaviour, Level 3 = unconventional communication, Level 4 = conventional communication, Level 5 = concrete symbols, Level 6 = abstract symbols (e.g. single words, single signs) and Level 7 = language (e.g. combining words or symbols). Qs = questions, Y/N = Yes/No. Classical CLN2 disease differences between communicative functions mastered: χ ² = 19.64, p = 0.0006.