Precision Medicine as a New Frontier in Speech-Language Pathology: How Applying Insights From Behavior Genomics Can Improve Outcomes in Communication Disorders.

PURPOSE: Precision medicine is an emerging intervention paradigm that leverages knowledge of risk factors such as genotypes, lifestyle, and environment toward proactive and personalized interventions. Regarding genetic risk factors, examples of interventions informed by the field of medical genomics are pharmacological interventions tailored to an individual's genotype and anticipatory guidance for children whose hearing impairment is predicted to be progressive. Here, we show how principles of precision medicine and insights from behavior genomics have relevance for novel management strategies of behaviorally expressed disorders, especially disorders of spoken language. METHOD: This tutorial presents an overview of precision medicine, medical genomics, and behavior genomics; case examples of improved outcomes; and strategic goals toward enhancing clinical practice. RESULTS: Speech-language pathologists (SLPs) see individuals with various communication disorders due to genetic variants. Ways of using insights from behavior genomics and implementing principles of precision medicine include recognizing early signs of undiagnosed genetic disorders in an individual's communication patterns, making appropriate referrals to genetics professionals, and incorporating genetic findings into management plans. Patients benefit from a genetics diagnosis by gaining a deeper and more prognostic understanding of their condition, obtaining more precisely targeted interventions, and learning about their recurrence risks. CONCLUSIONS: SLPs can achieve improved outcomes by expanding their purview to include genetics. To drive this new interdisciplinary framework forward, goals should include systematic training in clinical genetics for SLPs, enhanced understanding of genotype-phenotype associations, leveraging insights from animal models, optimizing interprofessional team efforts, and developing novel proactive and personalized interventions.

Virtual Post-Intervention Speech and Language Assessment of Toddler and Preschool Participants in Babble Boot Camp.

PURPOSE: Babble Boot Camp (BBC) is a parent-implemented telepractice intervention for infants at risk for speech and language disorders. BBC uses a teach-model-coach-review approach, delivered through weekly 15-min virtual meetings with a speech-language pathologist. We discuss accommodations needed for successful virtual follow-up test administration and preliminary assessment outcomes for children with classic galactosemia (CG) and controls at age 2.5 years. METHOD: This clinical trial included 54 participants, 16 children with CG receiving BBC speech-language intervention from infancy, age 2 years, five children receiving sensorimotor intervention from infancy and changing to speech-language intervention at 15 months until 2 years of age, seven controls with CG, and 26 typically developing controls. The participants' language and articulation were assessed via telehealth at age 2.5 years. RESULTS: The Preschool Language Scale-Fifth Edition (PLS-5) was successfully administered with specific parent instruction and manipulatives assembled from the child's home. The GFTA-3 was successfully administered to all but three children who did not complete this assessment due to limited expressive vocabularies. Referrals for continued speech therapy based on PLS-5 and GFTA-3 scores were made for 16% of children who received BBC intervention from infancy as compared to 40% and 57% of children who began BBC at 15 months of age or did not receive BBC intervention, respectively. CONCLUSIONS: With extended time and accommodations from the standardized administration guidelines, virtual assessment of speech and language was possible. However, given the inherent challenges of testing very young children virtually, in-person assessment is recommended, when possible, for outcome measurements.

Feasibility of a Proactive Parent-Implemented Communication Intervention Delivered via Telepractice for Children With Classic Galactosemia.

PURPOSE: This study evaluated the feasibility of Babble Boot Camp (BBC) for use with infants with classic galactosemia (CG) starting at less than 6 months of age. BBC is a parent-implemented intervention delivered by speech-language pathologists (SLPs) entirely via telepractice with the potential to increase access to early preventative interventions. We evaluated BBC feasibility based on acceptability, implementation, and practicality. METHOD: We obtained data from 16 parents of infants with CG (mean age at enrollment = 3.38 months) involved in a large randomized clinical trial of BBC. BBC uses a teach-model-coach-review approach to provide parents with strategies to support their child's communication development. Families completed, on average, eighty-one 15-min sessions over a 20-month intervention period. We drew data from surveys completed by parents at the end of the intervention period, intervention logs maintained by the SLPs, and intervention fidelity checks completed by research assistants. RESULTS: Data drawn from parent surveys, intervention logs, and intervention fidelity checks revealed high parent acceptability, high rates of completion and compliance, and low costs in terms of parent and clinician time. CONCLUSION: Results suggest that BBC is feasible for families of infants with CG, warranting further examination of BBC across a broader range of children with CG as well as other infants who are at predictable risk for speech and language impairment.

Three children with different de novo BCL11A variants and diverse developmental phenotypes, but shared global motor discoordination and apraxic speech: Evidence for a functional gene network influencing the developing cerebellum and motor and auditory cortices.

BCL11A is implicated in BCL11A-Related Intellectual Development Disorder (BCL11A-IDD). Previously reported cases had various types of BCL11A variants (copy-number variations [CNVs], singlenucleotide variants [SNVs]). Phenotypes included global, cognitive, and motor delays, autism spectrum disorder (ASD), craniofacial dysmorphology, and speech and language delays described generally, with only two reports specifying childhood apraxia of speech (CAS). Here, we present three additional children with CAS and de novo BCL11A variants, a p.Ala182Thr nonconservative missense and a p.GLu611.Ter nonsense variant, both in exon 4, and a 106 kb deletion harboring exons 1 and 2. All three children have fine and gross motor discoordination, feeding difficulties, and visual motor disorders. Intellectual and learning disabilities and disordered language skills were seen only in the child with the missense variant and the child with the deletion. These findings align with, and expand, previous findings in that BCL11A variants have significant and highly penetrant apraxic effects across motor systems, consistent with cerebellar involvement. The deletion of exons 1 and 2 is the smallest BCL11A CNV with the full phenotypic expression reported to date. The present results support previous findings in that BCL11A-IDD can result from BCL11A variants regardless of type (deletion, SNVs). A gene expression study shows that BCL11 is expressed highly in the early developing cerebellum and primary motor and auditory cortices. Significant co-expression rates in these regions with genes previously implicated in disorders of spoken language and in ASD support the phenotypic overlaps in children with BCL11A-IDD, CAS, and ASD.

Translating principles of precision medicine into speech-language pathology: Clinical trial of a proactive speech and language intervention for infants with classic galactosemia.

Precision medicine is an emerging approach to managing disease by taking into consideration an individual's genetic and environmental profile toward two avenues to improved outcomes: prevention and personalized treatments. This framework is largely geared to conditions conventionally falling into the field of medical genetics. Here, we show that the same avenues to improving outcomes can be applied to conditions in the field of behavior genomics, specifically disorders of spoken language. Babble Boot Camp (BBC) is the first comprehensive and personalized program designed to proactively mitigate speech and language disorders in infants at predictable risk by fostering precursor and early communication skills via parent training. The intervention begins at child age 2 to 5 months and ends at age 24 months, with follow-up testing at 30, 42, and 54 months. To date, 44 children with a newborn diagnosis of classic galactosemia (CG) have participated in the clinical trial of BBC. CG is an inborn error of metabolism of genetic etiology that predisposes up to 85% of children to severe speech and language disorders. Of 13 children with CG who completed the intervention and all or part of the follow-up testing, only one had disordered speech and none had disordered language skills. For the treated children who completed more than one assessment, typical speech and language skills were maintained over time. This shows that knowledge of genetic risk at birth can be leveraged toward proactive and personalized management of a disorder that manifests behaviorally.

Toward Preventing Speech and Language Disorders of Known Genetic Origin: First Post-Intervention Results of Babble Boot Camp in Children With Classic Galactosemia.

Purpose Babble Boot Camp (BBC) is a package of proactive activities and routines designed to prevent speech and language disorders in infants at predictable risk. It is implemented via parent training and currently undergoing clinical trial in children with a newborn diagnosis of classic galactosemia (CG), a metabolic disease with high risk of speech and language disorders. The purpose of this study is to provide updates to a previous pilot study and to present the first set of post-intervention results. Method The intervention and data collection occurred during child ages < 6-24 months, with follow-up assessments of speech and language at ages 2.5 and 3.5 years. Treatment targets included earliest vocalization rates, babble complexity, speech production accuracy, and vocabulary and syntactic growth. The oldest 15 children with CG (including three untreated controls) completed the first set of follow-up assessments. Aggregate data up to 10 months were available for 17 treated children with CG, six untreated children with CG, and six typical controls. Results At ages 7-9 months, babbling complexity, as measured with mean babbling level, was higher in the treated children with CG than in the untreated children with CG and the typical controls. Prior to 24 months of age, the treated children with CG had greater expressive but not receptive vocabulary sizes than an untreated control. Follow-up testing showed typical language scores for all 12 treated children with CG and typical articulation scores for 11 of these, whereas one of three untreated children with CG had low articulation and expressive language scores. Conclusions The BBC appears to be a viable intervention to support the speech and expressive language development of children with GC. Future studies will evaluate the relative contributions of the earliest and later BBC components to outcomes.

Comparing global motor characteristics in children and adults with childhood apraxia of speech to a cerebellar stroke patient: evidence for the cerebellar hypothesis in a developmental motor speech disorder.

Individuals with childhood apraxia of speech (CAS) have motor deficits in systems beyond speech and also global deficits in sequential processing, consistent with cerebellar dysfunction. We investigated the cerebellar hypothesis of CAS in 18 children and adolescents with CAS, 11 typical controls, an adult with a probable CAS history, and an adult with a history of a cerebellar stroke. Compared to the controls, children and adolescents with CAS had the greatest difficulty with rapid syllable repetition when alternating between two different syllables types, less difficulty when switching among three different syllables, and no difficulty when repeating the same syllable. They also showed difficulty with alternating but not repetitive key tapping. Motor speeds during the syllable repetition and key tapping tasks where correlated, consistent with a central motor delimiter that governs both systems. Participants with CAS obtained low scores in a test of fine motor ability, where the tasks required rapid integration of complex hand movement sequences. The adult with the probable CAS history obtained motor performance scores that generally resembled those in the children and adolescents with CAS, consistent with motor deficits that persist into adulthood. The participant with the cerebellar stroke history showed deficits in tests of fine and gross motor ability as well as balance. His repetitive and alternating key tapping was slow in the ipsilateral hand relative to the stroke lesion. The shared deficits in sequential motor functions among all participants with CAS and the cerebellar stroke patient are consistent with persisting cerebellar dysfunctions in CAS.

Starting to Talk at Age 10 Years: Lessons About the Acquisition of English Speech Sounds in a Rare Case of Severe Congenital But Remediated Motor Disease of Genetic Origin.

Purpose This study was conducted to observe speech development in a child whose onset of oral communication was extremely delayed. In rare cases, children are born with physical limitations that temporarily interfere with speech sound production. Whether the development of speech sound production follows the same trajectory as that in typical children at younger ages is not well understood. Method We present a child who was wheelchair-bound and communicated nearly exclusively via augmentative and alternative communication devices due to severe congenital motor disease and generalized hypotonia. At age 10 years, her condition improved dramatically with medication after a mutation in a dopamine-related gene was discovered, and she switched entirely to oral communication. Observation of speech development was based on chart reviews, video recordings, and direct testing at age 15 years. Results At age 4 years, the participant's attempts at speech showed a small phoneme inventory consisting of early-acquired phonemes and large numbers of common phonological processes. Following the medical intervention at age 10 years, mastery of velars occurred after age 12 years and mastery of liquids was still incomplete at age 15 years. Conclusions Findings are consistent with general growth trends in speech sound acquisition that are independent of chronological age. Theoretical considerations regarding the role of motor control in the invariant order of speech sound acquisition are posited, specifically regarding articulatory building blocks. Clinical recommendations include interprofessional management of children with complex motor disease and referrals to genetics professionals in the care of such children.

Toward a paradigm shift from deficit-based to proactive speech and language treatment: Randomized pilot trial of the Babble Boot Camp in infants with classic galactosemia.

Background: Speech and language therapy is typically initiated reactively after a child shows delays. Infants with classic galactosemia (CG), a metabolic disease with a known high risk for both speech and language disorders, hold the keys towards evaluating whether preventive treatment is effective when the risks are known at birth. We present pilot data from a randomized parallel trial of an innovative proactive speech and language intervention program, the Babble Boot Camp (BBC).  Method: Five children with CG, otherwise healthy, participated in the study from approximately 2 to 24 months of age. One of these was randomly selected as control receiving conventional management, which typically starts at age 2-3 years. A pediatric speech-language pathologist met weekly via telepractice with the parents in the treatment cohort. Parents implemented the prespeech, speech, and language stimulation and expansion activities according to the intervention protocol. The control child was still too young for conventional treatment. Primary outcome measures were speech sound production complexity in babble and speech and expressive vocabulary size. Secondary outcome measures were vocalization rates and developmental milestones in communication, motor, and cognition. The trial is ongoing. Results:  All four treated children had higher speech sound skills in babble, three had higher speech sound skills in meaningful speech, two had higher expressive vocabularies, three had higher global developmental scores, and two had higher vocalization rates, compared to the control child with CG. Discussion: Given the high risk for speech and language delays in children with CG, finding on-schedule abilities in two or more of the treated children but not the untreated child is unexpected under random conditions. The trends toward beneficial effects of the BBC on speech sound production, expressive language, and communication milestones warrant appropriately powered larger clinical trials with full randomization. Trial registration: ClinicalTrials.gov NCT03838016 (12 th February 2019).