THE LONGITUDINAL PROGRESSION OF COMUNICATION SKILLS OF INDIVIDUALS WITH SANFILIPPO SYNDROME TYPE B: A RETROSPECTIVE CHART REVIEW
A thesis submitted to the faculty of /\ 5 San Francisco State University : , In partial fulfillment of the requirements for the Degree SPEb
Master of Science
In
Communicative Disorders
by
Roderick Xavier Nepomuceno de Leon II
San Francisco, California
May 2017 CERTIFICATION OF APPROVAL
I certify that I have read The Longitudinal Progression of Communication Skills of
Individuals with Sanfilippo Syndrome Type B: A Retrospective Chart Review by
Roderick Xavier Nepomuceno de Leon II, and that in my opinion this work meets the criteria for approving a thesis submitted in partial fulfillment of the requirement for the degree Master of Science in Communicative Disorders at San Francisco State University.
Patti Solomon-Rice, Ph.D. Assistant Professor
Laura Epstein Ph.D. Associate Professor THE LONGITUDINAL PROGRESSION OF COMUNICATION SKILLS OF INDIVIDUALS WITH SANFILIPPO SYNDROME TYPE B: A RETROSPECTIVE CHART REVIEW
Roderick Xavier Nepomuceno de Leon II San Francisco, California 2017
Sanfilippo syndrome type B is a rare genetic disorder typically causing central nervous system failure, which significantly impacts speech and language skills. Individuals with this disorder will typically experience initial period of development in their communicative skills before experiencing signs of significant regression. This study aims to examine how their communicative skills progress and regress. Using a retrospective study of seventeen participants, the results demonstrate an initial progression of receptive and expressive language skills, which range from low-average to below average on standardized testing; but then starts to regress to below to significantly below average skills starting around 3 years old. This study indicates the need for further research regarding their communicative skills and future evidence-based practice.
I certify that the abstract is a correct representation of the content of this thesis
Chair, Thesis Committee PREFACE AND ACKNOWLEDGEMENTS
I would first like to thank my thesis advisor, Dr. Patti Solomon-Rice of the Communicative Disorders Program at San Francisco State University. The door to Professor Solomon-Rice's office was always open whenever I had questions regarding my research or writing. She steered me in the right the direction whenever she thought I needed it. I could not have asked for a better advisor.
I would like to thank my other thesis committee member, Dr. Laura Epstein. Your encouragement, insightful comments, and questions were deeply appreciated!
I profoundly express my gratitude to my parents, my family, friends, loved ones — especially my little cousin, Sabrina Gabriel— for providing me with inspiration, unfailing support, and continuous encouragement throughout my life.
Lastly, I would like to extend my gratitude to Neurodevelopment in Rare Disorders (NDRD) program at the Children's Hospital of the University of Pittsburgh Medical Center. This research would not have been possible without the data from Dr. Maria L. Escolar, Dr. Michele D. Poe, and the rest of the staff and families from NDRD.
This accomplishment would not have been possible without all of them. Thank you. TABLE OF CONTENTS
List of Table...... vi
List of Figures...... vii
List of Appendices...... viii
Introduction/Literature Review...... 1
Purpose of Study...... 10
Method...... 11
Results...... 16
Discussion...... 32
Limitations...... 35
Future Direction...... 36
Conclusion...... 37
Reference...... 38
Appendices...... 46 LIST OF TABLES
Table Page
1. Demographics of Participants...... 12 2. Number of participants with data reported across communication characteristics...... 16 3. Participants’ Receptive and Expressive Age Equivalency Scores...... 18 4. Communication Characteristics of Participants...... 28 LIST OF FIGURES
Figures Page
1. Changes in Receptive Language with Participants 1-6...... 25 2. Changes in Receptive Language with Participants 7-12...... 25 3. Changes in Receptive Language with Participants 13-17...... 26 4. Changes in Expressive Language with Participants 1-6...... 26 5. Changes in Expressive Language with Participants 7-12...... 27 6. Changes in Expressive Language with Participants 13-17...... 27
vii LIST OF APPENDICES
Appendix Page
1. Receptive Language Age-Equivalency Scores...... 46 2. Expressive Language Age-Equivalency Scores...... 50
viii 1
Introduction
Sanfilippo syndrome, otherwise known as Mucopolysaccharidosis (MPS) type III, is an autosomal recessive disorder cause by a deficiency in one of four enzymes needed to break down a complex sugar molecule called heparan sulfate (Delgadillo, O’Callaghan,
Gort, Coll, & Pineda, 2013; Valstar, Ruijter, Diggelen, Poorthuis, & Wijburg, 2008).
Each enzyme deficiency is further categorized into four subtypes: type A [heparan N- sulfatase], type B [a-N-acetylglucosaminidase], type C [heparan sulfate acetyl CoA: a- glucosaminide N-acetyltransferase, HGSNAT], and type D [N-acetylglucosamine 6- sulfatase] (Valstar et. al., 2008). Typically, heparan sulfate is created, broken down, and recycled in an outgoing process to keep the body healthy (National MPS Society, 2011).
If heparan sulfate molecules are not broken down correctly, they remain stored in the cells and accumulate, causing interference to normal cell function (Buhrman, Thakkar,
Poe, & Escolar, 2013; National MPS Society, 2011). Cells that functioned appropriately during the first few months of life progressively damage other cells, tissue, and different organs over time (Valstar, et. al., 2008; National MPS Society). The result is a multi system disease (Malm, & Mansson, 2010) that affects speech and other cognitive skills, as well as motor skills to a lesser degree (Valstar, et. al., 2008; Ruijter, Valstar, van de
Kamp, Van der Helm, Durand, Van Diggelen,... & Wijburg, 2008).
Classification of Sanfilippo Syndrome Type B 2
Sanfilippo syndrome is classified as an autosomal recessive disorder. It is a hereditary
(genetic) disorder caused by two copies of an abnormal gene, requiring one copy from each parent for the disease to develop. Autosomal recessive disorders may be metabolic in nature, which are genetic conditions resulting in an enzyme deficiency that causes a molecule to be ineffectually broken down. A category of metabolic disorders is lysosomal storage diseases (LSD), which result from an enzyme deficiency in the lysosomes. Lysosomes are needed to break and recycle lipids, gycoproteins, or mucopolysaccarides for proper cell functioning. Mucopolysaccharidosis (MPS) is a type of lysosomal storage disease that creates a shortage or lack of enzymes to break down mucopolysaccarides, which are long chains of sugar molecules. A subdivision of MPS is
MPS III, or Sanfilippo syndrome, which results in the inability to break down a specific mucopolysaccarides called heparan sulfate. Sanfilippo type B, the focus of this study, is one of the four subtypes of Sanfilippo syndrome, and is a deficiency of a specific enzyme, a-N-acetylglucosaminidase (Valstar, et. al., 2008).
Acquisition of Sanfilippo Syndrome
All Sanfilippo syndrome subtypes are rare disorders that can be passed down through families. Individuals are born with two sets of chromosomes, one set from the mother, and the other set from the father. In Sanfilippo syndrome, both the mother and father must pass down the Sanfilippo syndrome gene in order for their offspring to acquire the disease. As a result, there is a 25% chance that the offspring will have the disease, and 3
there is a 75% chance that that offspring will have at least one copy of the gene making them a carrier as well (A Guide to Understanding Mucopolysaccharidosis III, 2013;
National MPS Society, 2011).
Genetics and Phenotypes
As Sanfilippo syndrome is a genetic disorder, it is important to understand the basics of genetics and phenotypes. A gene is a unit or region of DNA (the genetic code, composed of building block nucleotides in a specific sequence) that provides instructions to protein molecules so that the body functions as intended. A mutation in a gene permanently alters the DNA. There are over 100 different types of mutations reported that may lead to Sanfilippo syndrome type B (Valstar et. al., 2010). The most typical mutation for Sanfilippo syndrome type B is missense mutation, in which an incorrect sequence is in place through a mutation in a single DNA nucleotide. Mutation deletions, insertions and splice-sites could also occur. Research has shown that Sanfilippo syndrome type B mutations take place in the gene that encodes the enzyme (a chemical catalyst composed of proteins) known as a-N-acetylglucosaminidase (NAGLU), likely localized to chromosome 17q21.1 (Valstar, et. al., 2008; Kamp, Niermeijer, Figura, &
Giesberts, 1981).
A phenotype is the characteristic that appears for different types of the same species.
It is the realization of genes as expressed in a physical body. There are two phenotypes of
Sanfilippo syndrome: the classical subtype and the mild/attenuated subtype. Current 4
research has distinguished between these two phenotypes by the onset of symptoms, language development, and onset of regression (Weber, Guo, Kleijer, Kamp, Poorthuis,
& Hopwood, 1999). More research is needed to further evaluate the effects of the relationship between genotype and phenotypes for early detection, understanding the prognosis for treatment, and support medicinal purposes. (Zhao, Aronovich, & Whitley,
1998; Liem, Giesberts, Niepoth, & Staalman, 1976).
Incidence of Sanfilippo Syndrome
The estimated incidence of Sanfilippo syndrome is currently not well determined.
Based upon published studies, the incidence is estimated about 1 in 70,000 births (A
Guide to Understanding Mucopolysaccharidosis III, 2013). Sanfilippo syndrome is the most prevalent type of the MPSs (Valstar, et. al., 2008; Baehner et. al., 2005). The birth prevalence probably ranges from 0.28-4.1 per 100,000 births (Valstar, et. al., 2008).
However, due to new studies and wide variability of Sanfilippo syndrome across the globe, both the stated incidence and prevalence may not reflect the true incidence and prevalence. Data is even scarcer when attempting to determine the incidence and prevalence of Sanfilippo syndrome type B.
Geographic studies are beginning to determine which of the subtypes are more prevalent than the others. For example, type A is more common in northern Europe than types B, C, and D. Research shows that type B is the most prevalent subtype in southern
Europe and Brazil (Valstar, et. al., 2008; Baehner et. al., 2005; Coelho, Wajner, Burin, 5
Vargas, & Giugliani, 1997). There is an unpublished observation, which reports that the incidence of type B is 1 in 211,000 births (Weber et. al., 1999). Reports of the incidence and prevalence in America for Sanfilippo syndrome type B were not found. However,
Valstar et. al. (2008) stated a study from 1964 indicated the prevalence of Sanfilippo syndrome in Utah was 0.5-1 per 100,000 births. More research on the incidence and prevalence of Sanfilippo syndrome and its four subtypes is needed.
Typical Language Development
Language development in children with Sanfilippo syndrome type B differs from typically developing children. Before children learn to speak, there are pre-linguistic factors or milestones they learn to use to facilitate language development. Development of verbal imitation skills is an important pre-linguistic skills needed to facilitate early word production. Typically developing children should be verbally imitating adult words at approximately age 10 to 13 months (Buckley & Oliver, 1994; Abbeduto, Warren, &
Conners, 2007). Joint attention is another important pre-linguistics skill, which refers to the infant’s ability to focus on the other person participating in an interaction (primary joint attention), or focus on a shared object with the other person (secondary joint attention) (Abbeduto, et. al., 2007). This skill is essential for pragmatic language development such as initiating/maintaining communication, turn-taking, commenting, noticing communication breakdowns and adjusting communication depending on the communication partner. Joint attention develops from birth to 12 months. Other pre 6
linguistics skills include cooing from birth to 3 months, and rapid understanding of words from age 6-18 months (American Speech-Language and Hearing Association, n.d.).
First words start to appear between 7-12 months (Buckley & Oliver, 1994). Around
19 months to two years of age, toddlers build their vocabulary and begin to combine words to create phrases and sentences. At the same time, toddlers use a variety of communicative function beyond requesting such as describing, commenting and protesting. By age 3, they are producing sentences, listening and understanding simple directions, and carrying on short conversations. As preschoolers, typically developing children build their language skills using socially appropriate conversations containing simple and complex grammatical sentences (Abbeduto, et. al., 2007; Buckley & Oliver,
1994).
Typical Speech Development
Speech is the verbal means of communication including how sounds are shaped
[articulation]; how the vocal folds and breath control are used to produce sounds [voice]; and the rhythm of verbal output [fluency] (American Speech-Language and Hearing
Association, n.d.). Individual speech sounds, or phonemes, are mastered at varying ages depending on the language spoken. English-speakers master production of the sounds of
English by age 8. The earliest developing phonemes include /p/, /m/, /h/, /n/, /w/, and /b/ and these phonemes are expected to be mastered [age 3]. Slightly later developing 7
phonemes consist of /k/, /g/, /d/, /t/, /r)/, /f/, and /j/, which are mastered by age 4 or later
(Sanders, 1972).
Additional aspects of speech development include voice and fluency. Voice disorders may include difficulties such as a hoarse or breathy vocal quality, or resonance difficulties such as a hypernasal resonance (American Speech-Language and Hearing
Association, n.d.). Fluency disorders include stuttering, neurogenic stuttering, and cluttering. Stuttering consists of repetitions, prolongations, and blocks when producing sounds and syllable, which result in dysfluent speech. Many children demonstrate developmental stuttering, especially when young, but most children “recover” from their stuttering several months after the stuttering emerges (American Speech-Language and
Hearing Association). According to Guitar (2014), neurogenic stuttering is acquired and exacerbated by neurological damages and diseases such as strokes and Parkinson’s disease. Unlike “true” stuttering characterized by natural dysfluencies, neurogenic stuttering is characterized as a speech disorder presenting stuttering-like dysfluencies.
Guitar (2014) also defined cluttering is rapid speech that is difficult to understand accompanied by mumbling words, omitting syllables, and slurred speech. People who clutter may produce dsyfluencies such as fillers incomplete phrases, word and phrase repetition, revisions, and hesitations.
Language and Speech Development of the Sanfilippo subtypes A and C 8
There have been some studies addressing the speech and language development of subtypes A and C. Results have shown that individuals with these two subtypes have typical language development at birth, and then start to see signs of regression after 24 months. Due to wide variety of phenotypes-genotypes, regressions may be fast or slow
(Valstar, et. al., 2008; Meyer et. al., 2007; Ruijter et. al., 2008; Buhrman, et. al., 2013).
One of Sanfilippo syndrome's characteristics is a developmental delay (Valstar et. al.,
2008). Speech is usually affected before motor regression. Speech development is often delayed and articulation is imprecise, and some individuals may not speak at all. Mild- phenotype patients with type C produce mumbling speech with decreased intelligibility.
Receptive and expressive language development in type A is also affected (Buhrman, et. al., 2013).
Hearing Impairment in Sanfilippo Syndrome
Hearing impairment is common with Sanfilippo syndrome. Ear, nose, and throat infections are frequent when these individuals are young (Valstar et. al., 2008). However, the accuracy of the results of hearing screenings might be affected by challenging behaviors and genetic mutations (Van De Kamp, Pelt, Liem, Giesberts, Niepoth &
Staalman, 2008; Valstar et. al., 2008; Andria, Natale, Giudice, Strisciuglio, & Murino,
2008). As a result, it is possible that hearing loss is not experienced in Sanfilippo syndrome types A, B and C (Van Schrojenstein-De Valk, Van De Kamp, & Reynolds,
1987; Buhrman, et. al., 2013; Berger-Plantinga, Vanneste, Groener, & Schooneveld, 9
2004). When hearing loss is present, auditory deficits are typically presented as a mixed hearing loss (Heldermon, Hennig, Ohlemiller, Ogilvie, Herzog, Breidenbach,... & Sands,
2007).
There is insufficient literature to distinguish hearing status differences between the classical and mild phenotypes of Sanfilippo syndrome. More research is needed to understand the impact of hearing loss on the speech and language skills of individuals with both (Heldermon et. al., 2007; Van De Kamp et. al., 2008).
Cranial and Facial Dsymorphisms
Facial deformities are also common, yet mild, in individuals with Sanfilippo syndrome (Valstar, et. al., 2008; Agrawal, Meshram, Vagha, Swamkar, & Palandurkar,
2012; Van De Kamp, et. al., 2008). Regarding labial structure, the lower lip tends to be thick and protruded while the upper lip upturned and the philtrum protrudes. Also, gum hypertrophy has been reported to be apparent (Danks, Campbell, Cartwright, Mayne,
Taft, & Wilson, 1972). Regarding ear deformities, helices tend to be thick at a variety of levels. Other cranial dsymorphism are macrocephaly or an abnormally large head (Van
De Kamp et. al., 2008). Coarse hair and thick nares are other common features (Danks et. al., 1972; Van De Kamp et. al., 2008). Overall, reports state that facial and cranial dsymorphism are mild or absent in individuals with Sanfilippo syndrome, specifically
Sanfilippo type B (Valstar, et. al., 2008). 10
Purpose of the study
Although the disease is uncommon, there is a need for a variety of professionals to treat individuals with Sanfilippo syndrome and their families. These professionals need to be familiar with the disease to provide appropriate services (Alpern, 1992). Literature on the natural progression of Sanfilippo syndrome type B is scarce (Valstar et. al., 2010;
Valstar, et. al., 2008). Classifying the course of speech, language, motor, and behavioral development could facilitate future treatment decisions (Buhrman, et. al., 2013).
There have been studies about the natural progression on subtype A and C, which includes a description of their language development. Although there is not sufficient research on the natural progression on type D and more research is needed for types A and C, there is less literature on the natural progression on type B, which is a more common subtype apart from type A (Valstar et. al. 2008; Meyer et. al., 2007; Ruijter et. al., 2008; Buhrman, et. al., 2013). Therefore, the purpose of this research is to describe the progression of communicative skills in individuals with Sanfilippo Syndrome type B. 11
Method
Research Design
The design of this study is a retrospective chart review. A retrospective study uses existing data that has already been recorded for reasons other than research (Hess, 2004;
Mantel & Haenszel, 1959). Existing data for this study was obtained through the
Neurodevelopment of Rare Disorders (NDRD) program at the University of Pittsburgh
Medical Center-formally the Neurodevelopment Function of Rare Disorders (NFRD) at the University of North Carolina. Participant medical records included final reports, speech and language evaluation reports, and speech and language test protocols. Through retrospective chart review, the researcher followed the longitudinal progression of communication skills of a rare disease in a feasible time without seeing or identifying the patients (Hess, 2004; Wilkinson, 2016; Mantel & Haenszel, 1959).
Participants
To be eligible for the current study, participants met the following criteria:
o Classical/Severe phenotype of Sanfilippo syndrome type B.
o Participant/Proxy consent
o Medical files must in the NDRD database by the start of the research date
o Medical files included completion of a speech and language evaluation.
Seventeen participants met the inclusion criteria for this study.
Demographics of the participants were as follows. The participants were born between the years 1996 through 2012. Seven out of seventeen participants were female 12
while the rest were male. Six participants were from a foreign county (Pakistan, Saudi
Arabia [2 siblings], Greece [2 siblings], and Spain). Three participants were bilingual in
English and another language (Pakistani or Arabic). Two participants were monolingual speakers of Greek, one participant was a monolingual speaker of Spanish, and the rest were monolingual speakers of English. Six participants received umbilical cord blood transplantation (UCBT), which may improve somatic symptoms such as joint mobility, lung function, liver volume, and growth. Four other participants were participating in a confidential clinical medication trial (CT). Table 1 provides a summary of the participant’s demographics, including the number of available reports used for data.
Table 1: Demographics of Participants
UCBT, Number Country of Participant Gender Languages CT, or of Origin neither Reports 1 Female USA English Neither 2 Pakistani and 2 Female Pakistan Neither 1 English 3 Female USA English UCBT 2 4 Male Greece Greek UCBT 1 Saudi Arabic and 5 Male Neither 1 Arabia English 6 Male USA English CT 4 7 Female Spain Spanish CT 4 8 Male USA English Neither 2 9 Male USA English UCBT 7 10 Male USA English Neither 1 11 Female USA English UCBT 7 12 Male Greece Greek UCBT 1 Saudi Arabic and 13 Female Neither 1 Arabia English 13
14 Male USA English Neither 1 15 Male USA English UCBT 5 16 Female USA English CT 4 17 Female USA English CT 3
Procedures
The procedures for this study consisted of reviewing the medical reports of individuals with Sanfilippo syndrome type B. Data was acquired from the
Neurodevelopment in Rare Disorders (NDRD) program by the primary researcher.
Available speech and language reports, developmental reports, and assessment protocols were extracted from the participants' files. Standardized testing results from the assessment protocols were organized into tables for quantitative analysis using age- equivalency scores (Martin et. al., 2008). A coding system was created to find themes, subthemes and trends in the speech and language evaluation reports and developmental reports. After data was coded, the data was organized for quantitative and qualitative analysis of each participant’s communication skills and how those skills progressed or regressed.
Independent Variable
The independent variable is the content of the medical reports, consisting of extracted speech and language evaluation reports, developmental reports, and assessment protocols.
Dependent Variable
Several dependent variables were identified for this study, coded as themes and subthemes. Speech and language evaluation reports and developmental reports were 14
reviewed to note possible themes. Then, the data was coded based on "Receptive
Language" and "Expressive Language." After data was sorted, the researcher reviewed the coded data again to determine subthemes within "Receptive Language" and
"Expressive Language" (Shibata, 2015; Seidman, 2013). Several sub-themes emerged from the reports:
• age-equivalency scores from standardized testing
• language development milestones
• non-verbal communication
• spoken words, phrases, and sentences
• articulation/intelligibility
• morphology and parts of speech
• following commands and identifying objects
Speech and Language Data
The following speech and language data was obtained:
1) Age-equivalencies from assessment tools including the Preschool Language
Scale, Fourth Edition [PLS-4] (Zimmerman, Steiner, & Pond, 2002); the Mullen
Scales of Early Learning (Mullen, 1995); and the Receptive-Expressive Emergent
Language Test, Second Edition [REELS-2] (Bzoch & League, 1991).
2) Language development milestones describing pre-linguistic skills such as
babbling, cooing, and vocalizations, as well as emergence of first words.
3) Non-verbal language such as pointing and other gesturing. 15
4) Spoken words, phrases, and sentences including the number of words produced,
how many words were combined into phrases and sentences, as well as how often
participants used two or more word combinations.
5) Articulation and intelligibility including emerging/mastering speech sounds,
frequency of speech sound errors, and the overall intelligibility of utterances.
6) Morphology and parts of speech including use of grammatical units attached to
base words (verb + -ing) as well as variety of nouns, verbs, adjectives and other
parts of speech produced.
7) Receptive language skills including following commands, following 1-2 step
directions and identifying objects such as people, common items, actions, and
prepositions. 16
Results
Participant data across subthemes was incomplete for many of the participants. Of
the 17 participants, 100% had age equivalencies reported for receptive and expressive
language, 100% of participant data reported information about language development
milestones for prior to word onset and 47% of participant data reported emergence of first
words. Non-verbal communication was reported for 17%. Spoken words, phrases and
sentences were reported for 94%. Articulation and intelligibility was reported for 35-
41%. Morphology and parts of speech were reported for 35%. Lastly, following
commands and identifying objects were reported for 100% of participants. Table 2
summarizes the number of participants with data reported across the types of
communicative characteristics of participants with severe phenotype of Sanfilippo
syndrome type B.
Table 2: Number of Participants with Data Reported across Communication
Characteristics.
Number of Subtheme Communication Characteristics participants Age- Receptive language 17 Equivalency Expressive language 17 2 Language Babbling and cooing Development 8 Milestones First words Gestures Non-Verbal 3 Pointing Communication Body language and facial expression 17
Spoken Words, More than 1 word 14 Phrases, and Averaging 7 to 10 words 4 Sentences Word combinations 4 Early consonant sounds (e.g. bilabials) 6 Articulation/ Later developing sounds (e.g. fricatives, liquids) Intelligibility 7 Intelligibility
Morphology Morphological units 2 and Parts of Speech Verbs, pronouns, and nouns 6 Following Following 1-step commands 13 commands and identifying Identifying common objects 17 objects
Receptive and Expressive Age Equivalencies
Receptive and expressive age equivalencies were reported for all participants
using the PLS-4, Mullen Scales, and REELS-2. In the area of receptive language, the
highest age equivalency was 46 months with age equivalencies ranging from 1 month
to 46 months. In the area of expressive language, the highest age equivalency was 50
months with age equivalencies ranging from 1 month to 50 months. Age
equivalencies for receptive and expressive language are reported in Appendices A
and B.
Many participants regressed in their scores for both receptive and expressive
scores, regardless of whether they received umbilical cord blood transplantation or
ongoing clinical trials. SLPs frequently reported challenging behaviors such as poor 18
task tolerance, increased aggression, and distractibility, impacted the ability to obtain
accurate age equivalencies. For example, participant 6 initially refused to complete
tasks and often required redirection.
Some participants demonstrated progression in their skills. For example,
participant l l ’s age equivalency increased from 9 months to 17 months in receptive
language between the ages of 6 and 7. Likewise, participant 17’s age equivalency
increased from 18 months to 26 months in expressive language between the ages of
3.5 and 4. Table 3 lists the highest receptive and expressive age equivalency scores,
as well as the final age equivalency scores, if multiple receptive and expressive
language age equivalencies were obtained.
Table 3: Participants ’ Receptive and Expressive Age Equivalency Scores
Received Highest Final Transplantation Receptive/Expressive Receptive/Expressive Participant (UCTB), Clinical Age Equivalency Scores Age Equivalency Score Trials (CT), or neither in months in months 1 Neither 46/50 18/12
2 Neither 20/20 20/20
3 UCTB 27/28 22/24
4 UCTB 27/16 27/16
5 Neither 25/18 25/18
6 CT 34/31 18/23
7 CT 41/32 14/17 19
8 Neither 18/15 9/10
9 UCTB 25/26 13/22
10 Neither 25/20 22/20
11 UCTB 28/25 15/13
12 UCTB 11/6 3/6
13 Neither 9/16 9/16
14 Neither 3/12 3/6
15 UCTB 34/35 34/32
16 CT 14/15 8/14
17 CT 27/26 27/26
Language Development Milestones
Babbling and cooing were only described if participants were essentially non verbal. It may be assumed these pre-linguistic milestones were already met when first words emerged. First words were extracted by the available reports, with data initially obtained by parent interview/questionnaire. Eight of seventeen participants produced first words at approximately age 13-14 months with a range of 6 months (Participant
5) to 22 months (Participant 15). Three of seventeen participants were not verbalizing words in their reports and all were younger than 3 years old during their last available report. The overall average of the participants’ first words was delayed as compared to the average age range for typical development (7-12 months). 20
Non-Verbal Communication
Non-verbal communication, specifically gesturing, was frequently reported in evaluation reports. Reports noted that gestures aided receptive language for following commands/directions. Pointing was the most frequent type of gestures use (n=3), followed by body language and facial expressions.
Spoken Words, Phrases, and Sentences
Fourteen of seventeen participants verbalized words and phrases. Most participants produced novel words as early as 2-3 years old. Four participants produced 7-12 words by 2-3 years old. Regarding two outliers, participants 8 and participant 11 produced 50-100 words by age 4.
Participants producing words were reported to verbalize with 1-3 word phrases.
Many participants used phrases and short sentences. Four participants were reported to produce word combinations at an average of 23 months. The following are examples of phrases and sentences produced: “watch a movie” (participant 1 at 8.8 years old); “I see doggie” (participant 9 at 3.9 years old); “I want water” (participant
9); “I go bye-bye” (participant 16 at 3.2 years old).
Some participants demonstrated regression in expressive language. Participant 1 was “essentially non-verbal” at age 8.8, and was continually losing skills. Participant
6 had a slight decrease in number of words used from 3-4 word phrases at age 8.7 to
2-3 word phrases around 9-10 years old. Participant 13 was noted to be “no longer talking in sentences.” Participant 11 had a quick, yet significant change from 21
producing 2-3 word sentences at age 3.5 to being “essentially non-verbal” at 4.0 years old. Participant 17 regressed from using 12 words to 4 words by the age of 4.
Articulation/Intelligibility
Many reports did not discuss speech sound development. However, four participants’ speech sound repertoires were noted. The most frequent sounds produced were bilabial sounds such as /b/, /p/, and /m/. These early developing sounds were initially produced before 3 years old, as well as other early developing sounds produced less frequently, such as /d/, /h/, /w/. Reports of later developing sounds were scarce, although the following sounds were noted: participant 11 produced / J / at 4 years old. Participant 15 produced all consonants except / 0/, /■$/,
M3/, and /)/ by age 5.
Participants frequently produced sound substitutions, which impacted speech intelligibility. Age appropriate gliding of /w/ for /r/ was the most frequent substitution noted (n=3). Other sound substitutions noted were final consonant deletion, fronting and devoicing errors (e.g. /dau/ for cow, /mai/ for mine). Intelligibility was often described as “poor” due to the sound substitutions and limited sound repertoires.
Morphology and Parts of Speech
Productions of early grammatical markers, such as the present progressive -ing
(e.g. runnmg) and plural -s (e.g. books), are typically mastered between ages 2 and 4 years. This is approximately the same age that children with Sanfilippo syndrome type B peak before regression. Many reports did not discuss use of early morphemes. 22
However, participant 11 was reported not to be using the present progressive form
(“verb + ing”) despite understanding it, and participant 15 was reported to use regular plurals and present progressives, but lost production of these grammatical markers at around age 5.
Parts of speech refer to use of nouns, verbs, adjectives, etc. Verbs were reported in participant 9’s language example as he stated, “I want water.” Other verbal participants, such as participant 11, did not use verbs, although participant 11 produced 3-4 word utterances.
Following Directions and Identifying Objects
Thirteen participants had data discussing following directions. Eleven participants followed 1-step directions between the ages 2 to 9. Participant 11 was the only child that displayed emergence of this skill, as she could not follow directions at 2.7 years old, but demonstrated this ability by 3.5 years old. Two participants (3 and 15) progressed to following 2-step commands by age 3.5. Two other participants were noted to regress in following directions. Participant 8 followed 1-step commands at
3.8 years old but could not follow directions at 8.7 years old. Participant 9’s regression was slight as he followed 1-step direction without gestures at 4.4 years old but required gestures at 6.3 years old.
In terms of identifying objects, participants were able to recognize the following categories: participant’s name, family names, colors, body parts, common
[household] objects, spacial concepts (e.g. in, off, on), inhibitory words (e.g. no), and 23
action words. The most frequent category was common [household] objects, but this may be related to the testing used for each visit. Trends of progression and regression were inconclusive as the categories identification fluctuated across participants. For example, participant 6 recognized categories at age 8.5, then recognized body parts but not colors at age 9.2, and then named these categories.
Trends
The participants’ age equivalencies for receptive language are displayed in
Figures 1-3 and the participants’ age equivalencies for expressive language are displayed in Figures 4-6. Multiple tests, PLS-4, Mullen Scales, and/or REELS-2, were completed during participant visits. However, the graphs average all age equivalencies obtained per visit. More participants obtained age equivalencies within the average to low average range during the first few year of development. Then, beginning near ages 3-4, participants demonstrated a slowing or regression of age equivalencies, falling below the average range, which continued to regress or very slowly increase as they aged. For example, participant 11 ’s expressive language age equivalency decreased from 20 months at age 3.5, to 9 months at age 4, then increased to 12-13 months at age 6-8. Although all of participant 11 ’s age equivalencies were below the average range, the decline at age 4 was more significant, likely due to behavioral challenges impacting the participant’s performance. 24
The communication characteristics for each participant are summarized in Table
4. Notable trends in receptive language include participants typically following 1-2 step commands while, at the same time, identifying or responding to names, objects, body parts, some preposition, and other. Notable trends in expressive language include decreased speech intelligibility characterized by poor articulation, and delays in production of first words, word combinations, and morphological usage. Both speech production and expressive language skills worsen over time.
Between the ages of 2 and 3, receptive and expressive language skills slowly progress. However, a few participants continued to demonstrate progress through ages 5-6, and then began to show signs of regression within their communicative abilities. Generally, their test results indicated significantly below age level age equivalencies after age 5, regardless of whether the participants received transplantations or were participating in a clinical trial. 25
Figure 1: Changes in Receptive Language with Participants 1-6
0 1 2 3 4 5 6 789 10 11 12 Chronological Age (years)
Figure 2: Changes in Receptive Language with Participants 7-12
_ 12 ■Participant 7 | 11 10 ‘Participant 8
1 5 •Participant 9 c i= r: Participant 10 3 CT UK& ■Participant 11 # £ ■Participant 12 I
3 4 5 6 7 8 9 10 11 12 Chronological Age (years] 26
Figure 3: Changes in Receptive Language with Participants 13-17
Chronological Age (years]
Figure 4: Changes in Expressive Language with Participants 1-6
12 •Participant 1 11 % "Participant 2 1 10 9 I 8 ■"Participant 31 7 5 b ^Participant 4 ' 5 3 Participant S
I Participant 6 £ -5
Chronological Age (years} 27
Figure 5: Changes in Expressive Language with Participants 7-12
—12 - ’ Participant 7 m11 I 10 •Participant 8 S 9 - 8 Participant 9 2 7 ~ ? 01 6 - Participant 10 3 s - s 4 ■Participant 11 & 3 “ < AJ 2 ~ ‘ Participant 12 * 1 ~ s> 0 + < 0 3 4 5 6 7 8 9 10 11 12 Chronological A^e (years)
Figure 6: Changes in Expressive Language with Participants 13-17
12 ■Participant 13 11 IT 10 I • Participant 14 9 ■ s 3 8 Participant IS C 7 *
- £ 6 3 -Participant 16 IT * Lii S 41 4 * “Participant 17 i 3 i - 2 i 1 0 0123456789 10 11 12 Chronological Age (years] al 4 Cmuiain hrceitc o Participants of Characteristics Communication 4:Table
Spoken Language Non *verbal Partici words, Articu- Intelligi Morph Parts of Following Identifyin Development communi pants phrases, and lation bility speech commands g objects Milestone ology cation sentences Essentially Used to speak Follows Identifies Reported non-verbal 1 1 to 3 word 1 -step name and speech delay at 8.8 years common chunks commands old objects Identifies common Seven true 2 [b, m, n, d, objects words at 2.2 g] and preposi tions Began putting words Speech was First words at Limited use together and 3 understand Body 12 month of gestures talking in 2 to able at age parts 3 word 3.2 sentences None (doesn’t speak but Pointing; Common 4 make sounds uses 7-10 true [b„ p, m, d, items and for some vocalization words n,l] action at age 2,9 things) words Communicate s in single Pictures Pointing Follows 1- First words word Difficult to and 5 and facial step by 6 months utterances; understand expressions commands action put 2 to 3 words words
K> 00 al 4 Cmuiain hrceitc (continued) Characteristics Communication 4:Table
together around 20 months Identified Use 3 to 4 colors at age 8; steps until Not identified 6 age 10 using following body 2 to 3 word directions sentences parts, but not colors at age 9; Speaks more than 100 Articula words; began Identifies tion was speaking in 2 object described Does not Follows 1* First words at to 3 word function 7 as “poor” use step 1 Smonths sentences at and through all pronouns directions age 3; action visits (ages combined words. 3-11) some words at ages 10-1 L Followed Said single Identified 1-step words at age objects commands 3.7, but does Articula and Not using with First words at not combine tion was a pictures 8 gestures at gestures 15 months words. ‘problem’ at age 3, age 8 provided at Regressed to at age 8. but lost age 3.7, but non-verbal at this skill lost skill at age 8. by age 8. age 8. 9 First words at Uses Combined 2- Gliding Difficult Verbs, Follows 1- Identifies
VOto al 4 Cmuiain hrceitc (continued) Characteristics Communication 4:Table
12 months gestures 3 words errors at due to prepositi step objects at around age age 4.3 articulation ons and commands; age 3, 3.2, and 5 problems pronouns did this w/o some words including present gestures at prepositi combinations making age 4.4; ons at at age 4.4. multiple required age 4.3, Regressed to substitution the gesture and name 2 words s at age 3.8 at age 6.2, at age 6.2 phrases at age but does 6.2 not follow commands at age 7.4 Follows 1- Identifies Does not use 10 step usome words commands objects “imcompre Produced Sensible” phrases although Identifies Does not Possess* Start around ages Limited to mother objects, First words as use ing ives following 2-3.5, then stops, understand inhibitory 11 early as 10 tense, but present, 1-step became nasals, and 90%, words months understan but no commands essentially glides unfamiliar (no), and ds it verbs by age 3.5 non-verbal by listeners objects age 4 understand at 50% Babbling and Uses “not 12 cooing; no [b, p, m, d] gestures speaking'’ words yet Speaks about Identifies 13 12-15 words name and and “no obiects
u> o al 4 Cmuiain hrceitc (continued) Characteristics Communication 4:Table
longer talking in sentences” at age 4.2 Says about Follows l- five words at step 14 age 5.2; no [h, n, d, m] commands word with combinations gestures [w, m„ p, b, d, t, n, g, k, Difficult to z ,tj] Follows l- Used 2-word understand Identifies present at Plurals step combinations by age 2.3, Verbs body age 2.3; all present, commands First words at at age 2.2; but was and parts, 15 conso but lost at age 2.3; 22 months then 3-4 word understood pronouns colors, nants skill by 2-step combinations by familiar present and present but age 5 commands at age 3.5 listeners at objects at age 3.5 [6* 3id3, age 4.5 and j] at age 5 Used 50 Does not First words words by age Verbalized Uses follow l- Identifies 16 around 12 4, but then words gestures step objects months uses 4 words clearly commands by age 5. Uses 2 word Identify combinations Does not objects at age 3, uses Pronouns follow l- 17 and then 3-4 word present step colors by combinations commands age 4. at age 4. 32
Discussion
The results of this study indicate a period of progression of communication skills in individuals with Sanfilippo syndrome type B before experiencing signs of regression as is evident in the participant’s age equivalency performance. The participants' age equivalencies were initially within the low average and below average range, and they generally regressed as they got older. Most participants’ regression emerged between 3 to
6 years old, suggesting individuals with a classical phenotype of Sanfilippo syndrome type B might also regress during this age range.
Receptive language development progressed slowly with participants identifying items following 1 or 2-step commands between the ages of 2.3 to 8.8, rather than being typically mastered by age 2-3 years old (Brown, 1998). Identifying objects and categories were skills that fluctuated and worsened when challenging behaviors impacted overall performances. In general, receptive language skills showed development in these areas but were delayed as compared to typical peers.
Individuals with Sanfilippo syndrome understand basic communicative messages but may require communication partners to simplify and shorten messages to facilitate comprehension. Some participants benefitted from pairing gestures with commands. This suggests that communication partners combine messages with familiar non-verbal actions such as pointing, facial expressions, and body language.
Expressive language development also indicated progression followed by signs of regression. Participants' first words were slightly delayed, at 13-14 months compared to typically developing peers at 7-12 months. Participants spoke in 1-3 word phrases, with a 33
few producing short sentences. Regression with a reduction of word combinations or becoming non-verbal emerged as early as 3.5 years old.
While individuals with Sanfilippo syndrome type B demonstrated initial communicative development, they generally experience delayed skills. First words emerging slightly later than individuals with typical development, and then became further delayed in terms of word combinations, minimal articulatory development, and syntactical/morphological usage.
The results provide support for use of total communication to maximize communicative function. This may involve a combination of gestures, verbal output, and external visual tools (Beukelman, & Mirenda, 2013). Use of a simple AAC system may help prolong their communication skills, especially after signs of regression emerge. The results also suggest when and how much communication develops before it regresses for these individuals, which may be useful for selecting goals and interventions as skills begin to regress.
The results suggest the need for speech-language pathologists and other professionals to be more aware of natural course of Sanfilippo syndrome and other rare genetic diseases as sensitive issues emerge when talking with family members and other loved ones. Family members, especially parents who have a child recently diagnosed, may be struggling with acceptance of the diagnosis, and information about development or regression of the individual could lead to an emotional discussion. Also, counseling effectiveness is dependent on the clinician’s awareness of probable outcomes of the 34
disease, which may make family members hesitant to trust doctors, speech-language pathologists, and other service providers, whom are unfamiliar with the disease (Holland,
& Nelson, 2014; Scarpa, Almassy, Beck, Bodamer, Bruce, De Meirleir, & Kamin, 2011;
Hillen, de Haes, & Smets, 2011).
It is imperative for speech-language pathologists, especially school-based speech- language pathologists, to be mindful of the individual’s communication prognosis.
Speech and language interventions in the schools may require a different approach because professionals should focus on maintaining communicative skills as well as developing skills if appropriate. Ethical concerns could arise about the appropriateness of interventions and goals to increase and maintain functional communicative outcomes.
Speech-language pathologist might also need to consider dysphagia-based treatment or provide in-service training for family members, caregivers, and school personnel if the regression affects the student’s safety during food and liquid intake (Mabry-Price, 2014;
Homer, 2008).
Sanfilippo syndrome type B is a rare, yet severe disease, which requires health and education providers to become familiar with its developmental and regressive prognosis in order to provide appropriate services. This study provides data addressing the course of communication development with this population, which could increase the knowledge and skills of professionals, and help facilitate the individual’s and family member’s quality of life. 35
Limitations
There were several limitations to this study. First, the availability of the data heavily relied on medical charts from the participants’ previous visits. Although the participants were not missing data within their files, they were seen irregularly, which may have impacted the data analyses.
Another limitation is that there was variation across the tests used for the speech- language evaluations. Although the Mullen Scales of Early Learning was frequently used during these evaluations, the speech-language pathologists would sometimes use other tests such as the Preschool Language Scale (PLS-4) or the Receptive-Expressive
Emergent Language Scale (REELS-2). This study would have benefited from consistently using a specific test for valid age equivalency comparisons.
Another limitation was the participant's behaviors. Challenging behaviors impacted performance, which may have resulted in less advanced demonstration of true developmental skills. Hearing loss may be common with individuals with Sanfilippo syndrome. Although the participant's hearing status could not be disclosed for possible conflict ion with another study, it is likely participants may have had hearing impairments, which may have negatively impacted their performance.
The largest threat to the validity of this study was that more than half of the participants received a treatment, umbilical cord flood transplantation or a confidential clinical trial. Therefore, the data may not accurately describe the natural course of the disease. 36
Future Directions for Research
Future research should address the natural progression and regression of communication skills of the disease, and compare the communicative course against the other subtypes of Sanfilippo syndrome. A comparison of the Sanfilippo syndrome subtypes is also necessary to note possible differences between subtypes of Sanfilippo syndrome and the communication skills of typically developing peers. Incorporating assessments such as the Functional Communication Profile would be useful to analysis their non-verbal communication (Kleiman, 2003). Conducting thorough speech-language evaluations annually is suggested for accurate and consistent longitudinal data tracking for this disease. Parent report instruments like the MacArthur-Bates Communicative
Development Inventories would be beneficial to incorporate for consistent longitudinal tracking if participants cannot consistently be evaluated in-person (Fenson, Marchman,
Thai, Dale, Reznick, & Bates, 2007).
Another suggestion is to analyze how hearing loss affects language development in individuals with Sanfilippo syndrome, since hearing loss was a potential threat to this study. This research is necessary to expand the literature by determining whether audiological intervention may increase or maintain communication skills.
The intent of the study was to expand our knowledge of the communication skills of children with Sanfilippo syndrome so that Speech-Language Pathologist and other professionals can provide appropriate and effective services. As adult dementia is also a 37
regressive disease, it may be appropriate to consider if evidence-based practice for individuals with dementia is beneficiary to these individuals with Sanfilippo syndrome since individuals with Sanfilippo syndrome experience similar regressing of communication skills, dysphagia, and the need for family/caregiver counseling and special diagnostic/treatment approaches. (Valstar et. al., 2008; Hegde & Freed, 2013;
Roseberry-McKibbin, & Hegde, 2016).
Conclusion
Individuals with classical phenotypes of Sanfilippo syndrome type B tend to develop communication skills up to approximately ages 2-3. Then, their communicative growth significantly slows down and starts to regress with significantly below average skills. Understanding the progression and regression of the communication skills of individuals with Sanfilippo syndrome type B will greatly assist speech-language pathologists and other working professions determine and provide the most appropriate services in the schools, medical settings, and other settings. 38
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Appendix A
Receptive Language Age-Equivalency Scores
Visit Age (in Mullen PLS-4 REELS-2 Participant Number decimals) (in months) (in months) (in months)
1 1 4.8684 - 44 -
2 5.7181 - 46 -
3 6.343 10 15
4 8.7993 8 18
2 1 2.2231 13 20 18
3 1 3.0592 27
2 3.2115 22
4 1 2.9221 27
5 1 2.6836 25
6 1 8.7636 34
2 9.224 22
3 10.0438 18 47
7 1 3.9665 41
2 10.2850 16
3 10.7949 16
4 11.3515 14
8 1 3.7664 18
2 8.7335 9
9 1 3.2181 23
2 3.8651 25
3 4.3996 25
4 6.2916 11
5 6.2916 13
10 1 2.6535 25
2 5.7209 22 - -
11 1 2.7165 28 25
2 3.5800 10 3 4.0433 8
4 6.0361 9
5 7.0202 17
6 8.2319 15
12 1 1.2664 11
13 1 4.2708 9
14 1 5.1973 - 11
2 7.1677 1 3 3
15 1 2.3245 22
2 2.7467 24 25
3 3.2264 23 23
4 3.5526 27 27 33
5 4.48928 34 21 33
16 1 4.3201 11
2 4.8190 14 49
3 5.3700 8
17 1 3.0427 14
2 3.5361 14
3 4.0926 27 Appendix B
Expressive Language Age-Equivalency Scores
Visit Age (in Mullen PLS-4 REELS-2 Participant Number decimals) (in months) (in months) (in months)
1 1 4.8684 - 43 -
2 5.7181 - 50 -
3 6.3431 22 26
4 8.7993 12
2 1 2.2231 15 20 18
3 1 3.0594 28
2 3.2155 24
4 1 2.9221 16
5 1 2.6836 18
6 1 8.7636 31
2 9.2242 21
3 10.0315 23 51
7 1 3.9665 32
2 10.2850 22
3 10.7949 22
4 11.3514 17
8 1 3.7664 15
2 8.7335 10
9 1 3.2181 26
2 3.8651 24
3 4.3996 26
4 6.2993 20
5 7.4205 22 -
10 1 2.6535 24
2 5.7209 20 -
11 1 2.7165 21 25
2 3.5800 20
3 4.0433 9 4 6.0361 12 ' 5 7.0202 13
6 8.2319 13
12 1 1.2664 6
13 1 4.2708 16
14 1 5.1973 - - 12
2 7.1765 6 3 1
15 1 2.3245 23 24
2 2.7467 35 28
3 3.2264 35 28
4 3.5526 31 31 33
5 4.4928 32 24 30
16 1 4.3291 15
2 4.8190 14
3 5.3700 14
17 1 3.0475 21 2 3.5361 18
3 4.0926 26