Congenital or Early Developing Neuromuscular Diseases Affecting Feeding, Swallowing and Speech – A Review of the Literature from January 1998 to August 2021

Spinal muscular atrophy (SMA)

The aim of the study by van der Heul et al was to assess feeding and swallowing problems in 16 infants with SMA type 1, including five who were treated with Nusinersen [17]. All eventually developed swallowing problems. Tube feeding had to be initiated when they were 8–12 months old, even though their gross motor function improved during the same period.

A retrospective chart study reviewed the swallowing dysfunction in patients with SMA type 1 [18]. All patients had clinical evidence of oral motor dysfunction because of masticatory and facial muscle weakness, limited mouth opening, drooling, and difficulty chewing solid food. Swallowing deteriorated around six months of age and tube feeding was initiated. All subjects were eventually dependent on a feeding tube. The period from total oral feeding to tube feeding varied between five and twelve months. The authors recommend an individualised approach to the management of swallowing dysfunction in SMA type 1 due to a wide variation among patient degree of deterioration of swallowing function before 12 months of age.

Feeding/eating and weight gain problems have been reported in SMA type 2 and 3 and confirmed in several articles [19–22]. For SMA type 2, the following has been reported: weight more than 2SD above the median (5%), weight less than 2SD below the median (37%), chewing difficulties (28%), limitation of the ability to open the mouth (30%), and swallowing difficulties (25%) [19]. Based on these results, it was concluded that the standards of care should include monitoring and management of feeding difficulties and weight gain. In a study by Wadman et al. (2021), feeding difficulties were present in 60% of children and adolescents with SMA type 2 with a median age at onset of 6.5 years (0–16.5 years) [20]. Underweight and weight gain problems was a major issue in up to 57% of patients. The authors emphasizes that treatment strategies should be tailored to the needs of the individual patient.

The underlying mechanism of dysphagia in children with SMA type 2 has been investigated [21]. The study concluded that it was caused by muscle weakness and impaired mobility of the tongue and submental area in combination with a compensatory head posture. The authors recommend the use of an adapted posture during meals and ending the meal with water.

The prevalence and risk factors of dysphagia in patients with SMA type 2 and 3 have been studied in a questionnaire survey [22]. The most common risk factors reported for dysphagia in patients with SMA type 2 and 3 were choking (30.6%), difficulty transporting food to the mouth (20.4%) and difficulty chewing (20.4%). The severity of the dysphagia was closely related to current overall motor function, and patients with dysphagia had an increased risk of underweight and aspiration pneumonia. In this study, age was not an independent risk factor for feeding and swallowing difficulties.

Studies have been performed on reduced maximum mouth opening and its association with dysphagia in SMA type 1–4 [23]. The results showed that reduced maximum mouth opening is common in SMA types 1–3a. It was associated with dysphagia and concluded to be a sign of bulbar dysfunction. The main cause was found to be a fatty degeneration of specific mouth-opening muscles.

Self-reported bulbar problems such as jaw problems (34%), fatigue associated with mastication (44%), choking (56%) and intelligibility problems were frequently reported in patients with SMA [24]. Bulbar complaints were significantly, although weakly, correlated with reduced mouth opening in patients with SMA type 2.

Van der Heul et al. (2021) have studied mastication in patients with SMA types 2 and 3 [25]. Reduced maximum mouth opening was associated with mastication problems. Non-ambulatory patients demonstrated inefficient mastication. Muscle ultrasound of the mastication muscles showed an abnormal muscle structure in 90% of both ambulatory and non-ambulatory patients. An increase in bulbar problems was reported by patients who were older than 30 years of age and had a milder form of SMA.

A study by Zappa et al. (2021) investigated language comprehension and speech in children with SMA type 1 [26]. Although speech and motor function were severely compromised, children with SMA type 1 presented language comprehension within the normal range. Speech impairment was related to global motor impairment. Parents often report that they perceive their child with SMA type 1 to have greater receptive than expressive language skills [27]. They highlight the importance of speech-generating devices to improve the ability to communicate and thereby also increase quality of life.

One of the largest international studies designed to identify the phenotypic profile and relative importance of individual symptoms in 359 adults with SMA (292 were diagnosed with SMA type 1-3) was performed by Mongiovi et al. (2018) [28]. The symptomatic burden varied based on the patient-reported SMA type. SMA type 1 had a higher prevalence of communication difficulties than all other SMA types and a higher prevalence of choking and swallowing issues compared to types 3 and 4. Gastrointestinal issues, communication difficulties, and choking or swallowing issues all differed between SMA type 2 and 3. Similarly, problems with choking or swallowing issues differed between SMA type 2, 3 and 4. There was no significant difference in the prevalence of these problems between SMA type 3 and SMA type 4. Breathing difficulties, choking or swallowing issues and communication difficulties were significantly less prevalent in the group that walked independently.

The “Consensus statement on standard of care for spinal muscular atrophy” (2007) includes specific recommendations for gastroenterology and nutrition [29]. In “Diagnosis and management of spinal muscular atrophy: Part 1” (2018), the consensus recommendations for nutrition, swallowing and gastrointestinal management are updated [30]. There are also literature reviews regarding feeding and swallowing in SMA [31, 32].

In recent years, there has been very rapid development of drugs in the treatment of SMA with a positive effect of the progression of the disease [33–35]. In 2016, Nusinersen (marketed as Spinraza) was approved for the treatment of SMA. In 2019, the Food and Drug Administration (FDA) approved Onasemnogene abeparvovec (Zolgensma, formerly AXS-101), the first gene therapy approved to treat children younger than two years with SMA. Risdiplam was approved for the treatment of SMA in adults and children two months and older in August 2020. The study by van der Heul et al. (2020) is the only study in this review that includes patients with SMA who have received any of the drugs [17].

Charcot-Marie-Tooth disease (CMT)

No study was found that described feeding, swallowing, saliva control or speech in early onset CMT.

Congenital myasthenic syndrome (CMS)

Congenital stridor and feeding difficulties during the neonatal period are common in different forms of CMS [36, 37]. Kinali et al. reported on 46 children with CMS, six had stridor (13%), 12 respiratory insufficiency (46%) and 29 (63%) feeding difficulties as neonates [36]. In a study of 23 children with CMS and a mutation in the DOK7 gene, Klein et al. [37] found that 11 (48%) had stridor and 13 (57%) had feeding difficulties at birth [37]. Seven of the children with stridor had documented vocal cord palsy. Stridor and vocal cord palsy were also found in a retrospective case review in 6 of 11 (55%) children with CMS and a mutation in the DOK7 gene [38]. In a retrospective study of 538 children with velopharyngeal inadequacy, four children with myasthenia gravis were identified to have velopharyngeal incompetence [39].

Juvenile myasthenia gravis (JMG)

In a study of 119 children with JMG, 7.5% were diagnosed with dysphagia [40]. Bulbar symptoms may be present in JMG with more generalized skeletal muscle involvement [41]. In a clinical study of JMG in southern China, less than 1% of 327 children had bulbar weakness [42]. No literature describing specific bulbar impairment in JMG was found.

Arthrogryposis multiplex congenita (AMC)

No study was found that described feeding, swallowing, saliva control or speech in AMC.

Becker muscular dystrophy (BMD)

If their physical functional status is at the same level, patients with BMD are found to have chewing and swallowing problems like those observed in patients with DMD (see below) [43, 44]. Language and speech delay is common in BMD [45].

Congenital myopathy (CM)

Hypotonia at birth, weak crying, respiratory disease and feeding difficulties are common in infants with CM and many are dependent on ventilatory support and tube feeding during childhood [46, 47]. In a clinical and neurologic examination of 10 patients (3–25 years) with the childhood onset form of centronuclear myopathy, hypotonia at birth, weak crying and feeding difficulties were frequent. Weakness of the masticatory and facial muscles were other characteristic findings [46]. In a report of 143 individuals with nemaline myopathy (NM) (including six with adult onset), 79 (55%) had feeding difficulties and 75 (52%) significant respiratory disease during the first year of life [47]. Of 66 patients with CM assessed over a 5-year period, 35% required ventilatory support and/or enteral feeding [48]. The natural history of 125 patients with CM was studied at a paediatric neuromuscular centre [49]. It was found that bulbar involvement was present in 46.4% and gastrostomy placement in 28.8%.

The clinical history and physical examination of 57 individuals with NM (1–57 years) revealed that 51% required feeding tube [50]. Bulbar function was examined using two drooling scales and a slurp test (measuring the time to drink 4 oz of water through a straw). Thirty-eight individuals participated in the drooling tests and 35% had severe, 16% moderate, 8% mild and 41% no drooling. The results from the drooling frequency test showed that 11% had constant, 32% frequent, and 18% occasional drooling. All 23 individuals who attempted the slurp test had abnormal values.

The “Consensus statement on standard of care for congenital myopathies” (2012) includes recommendations for gastroenterology, nutrition, speech, and oral care [51].

Congenital muscular dystrophy (CMD)

Feeding problems in 14 children (2–14 years) with merosin deficient CMD were investigated in a study by Philpotin et al. [52]. The children had been followed every six months during six years. The examinations included feeding history, mealtime observations, assessment of oral anatomy and VFSS. The children were found to have a deviant oral anatomy and difficulties with chewing and swallowing that progress with age. Six children (43%) were at risk of silent food aspiration and had recurrent chest infections. Gastro-oesophageal reflux was a common finding. In a Japanese study of 207 patients with Fukuyama congenital muscular dystrophy (FCMD), 22% had dysphagia [53].

The “Consensus statement on standard of care for congenital muscular dystrophies” (2010) includes recommendations for gastroenterology, nutrition, and speech [54].

Duchenne muscular dystrophy (DMD)

The Sydney Swallow Questionnaire (SSQ) was used to compare patients with DMD without dysphagia to patients with DMD with dysphagia [55]. The patients with dysphagia reported significantly higher scores on “Difficulty swallowing thick liquids”, “Cough or choke when swallowing liquids”, “Ever cough up or spit out during meals”, “Difficulty starting a swallow”, “Interference with quality of life”, gastrointestinal involvement (gastro-oesophageal reflux and constipation) and weight gain.

In a survey of 118 patients with DMD (13–35 years), the results from a questionnaire showed that chewing difficulties are frequent and increase with age [58]. van den Engel-Hoek et al. (2016) assessed chewing in 72 patients with DMD of different ages (4–28 years) [56]. Food adaptation and chewing problems were observed in the early stages of the disease and mastication became increasingly effortful with age. Progressive chewing dysfunction was reflected by an increasingly abnormal echogenicity of the masseter muscle and reduced occlusal contacts.

The relationship between tongue pressure during water swallowing and the shape of the palate was studied in nine boys with DMD and compared with healthy controls [57]. An intra-oral tongue pressure measuring system was used and the width and depth of the palate were measured from maxillary dental casts. The width of the palate was significantly greater in the patients with DMD compared with controls. A negative correlation was found between tongue pressure magnitude and the depth of the palate.

When patients with DMD answered a questionnaire including questions about feeding difficulties, there were few clinical signs of swallowing difficulties; however, the authors comment that an objective swallowing assessment would be needed to detect minor signs of aspiration [58]. Gastro–oesophageal reflux requiring treatment was rarely reported but almost half the study group complained of constipation. In a study of the prevalence of smooth muscle dysfunction in children with DMD, Manokaran et al. (2020) found that 21% had gastro-oesophageal reflux [59].

Different objective instruments for the assessment of swallowing were used in a study by van Engel-Hoek et al. [60]. Dysphagia in DMD was described as three consecutive stages and the underlying mechanisms of dysphagia were assessed. The results showed that oral muscles related to swallowing were progressively affected. Tongue hypertrophy was common in the early and late non-ambulatory stages. Most problems were found in the late non-ambulatory stage, presenting in both the oral and the pharyngeal phase of swallowing. Other clinical studies have confirmed that the late stage of the disease is the strongest risk factor for masticatory performance and that chewing difficulties in combination with a weak swallow may be the cause of choking [56, 61–63]. Impaired oral motor activity during swallowing has also been found in studies using surface electromyography [55, 60, 64].

The relationship between eating and digestive symptoms and respiratory function has been investigated in patients with DMD who were non-ambulatory and required non-invasive, mechanical ventilatory support [65, 66]. Eating and digestive symptoms were more closely correlated with respiratory function than with age in patients with advanced DMD [65].

The “DMD care considerations –Diagnosis and management of Duchenne muscular dystrophy, part 1” (2018) includes recommendations for nutrition, swallowing and gastrointestinal management [67].

Facioscapulohumeral muscular dystrophy (FSHD)

In their study of dysphagia in FSHD, Wohlgemuth et al. examined eight patients (26–53 years) four whom had childhood onset [68]. An orofacial examination and an evaluation of eating and drinking were carried out. Instrumental assessments with MRI of the tongue and VFSS were included. Weak lips (n = 8), weak tongue (n = 6), weak jaw (n = 6) and delayed oral and pharyngeal transport of food (n = 7) were frequent findings. Four patients had a small tongue.

Juvenile dermatomyositis (JDM)

The caregivers of 79 children with JDM participated in a structured telephone interview, including questions about their child’s clinical symptoms, and 44% reported dysphagia [69]. In a study of oropharyngeal dysphagia in children with JDM by McCann et al. (2007) the aim was to establish predictive factors that could identify children at risk of aspiration [70]. Fourteen children participated in a clinical examination and a VFSS study. Of these, eleven children showed abnormal swallowing on VFSS but two of them could not be identified in the clinical examination alone. The authors therefore recommend that all children with active JDM should be referred for speech and language assessment and VFSS.

Mitochondrial myopathy (MiM)

The age at onset and the prognosis vary between diagnoses. In case of neonatal onset hypotonia, respiratory dysfunction and feeding impairment may be present as in Leigh syndrome [71]. No literature describing specific bulbar impairment in MiM was found.

Friedreich ataxia (FRDA)

Keage et al. studied dysphagia in 60 adults with FRDA, 45 (75%) of whom had childhood onset [72]. The participants were screened for dysphagia based on their case history and a quality-of-life questionnaire, and 59 (98%) of them reported dysphagia. Of these, 35 participated in an oromotor assessment and 38 in a swallowing study (VFSS). Thirty had both assessments. The most frequently affected oromotor domains were laryngeal, tongue, and respiratory function. The airway was significantly compromised in 13/38 patients and all patients who aspirated (n = 10) did so silently. The study results also indicate that dysphagia worsens with the duration and severity of the disease. The progression of dysphagia after one year was assessed in 23 adults with FRDA (87% had childhood onset) [73]. Swallowing-related quality of life, oral motor function and swallowing related health was stable after one year but more impaired tongue, pharyngeal, and cricopharyngeal function was observed in the swallowing examination (VFSS). The impact of dysphagia on quality of life was investigated in 36 adults with FRDA (69% with childhood onset) [74]. The results showed that swallowing function decreases with overall reductions in quality of life.

Twenty patients (16–71 years) with FRDA (42% with childhood onset) and ten controls (15–68 years) participated in a study of speech motor function and intelligibility [75]. Acoustic analyses of audio recordings gave information about speech rate and pitch variation. The most affected speech dimensions were respiration, voice quality, voice instability, articulation, and tempo. Vocal instability could predict ataxia severity. Tempo was correlated with disease duration and articulation could predict the intelligibility score. Speech and voice samples from 36 adults with FRDA (56% with childhood onset) and 30 controls were collected for acoustic and perceptual analysis [76]. Mild dysphonia including hoarseness, increased strain and altered pitch variability were characteristic findings. The onset and severity of the disease correlated with speaking rate and syllabic duration but not with dysphonia severity. The occurrence of nasality was investigated in 37 adults with FRDA (70% with childhood onset) and 20 controls [77]. Perceptual analyses showed that 27 had hypernasality and five hyponasality. A nasometry assessment including eight patients with FRDA and eight controls revealed a significantly higher nasality score in participants with FRDA compared with controls. Folker et al. (2012) investigated the respiratory, laryngeal, velopharyngeal, and articulatory systems of seven patients with FRDA (57% with childhood onset) using both perceptual and instrumental methods [78]. They found a variability in dysarthria associated with FRDA, especially concerning the presence of hypernasality and phonatory dysfunction.

Pompe disease (PD)

Significant feeding difficulties and respiratory distress are common in infant onset Pompe disease (IOPD), and continuous dysphagia monitoring is required [79–81]. Oropharyngeal swallowing was assessed in 13 children with IOPD, 0.5–16.1 months old, before initiation of Enzyme replacement therapy (ERT) [82]. Examination with VFSS showed that all children had dysphagia. The oral stage of swallowing was affected in 77% and the pharyngeal stage in 100%. Common symptoms were weak suck, pharyngeal swallow delay, pharyngeal residue, and airway invasion. Five had silent aspiration.

The frequency and consequences of facial muscle weakness, speech disorders and dysphagia were investigated a follow-up study of 11 long-term survivors of classic IOPD who were treated with ERT [83]. Facial muscle weakness was found in all children. Speech was assessed in four of the children who were found to have disordered articulation, hypernasality and reduced intelligibility. Six children took part in a swallowing examination and five were found to have “ineffective swallowing”, three penetration or aspiration, and two reduced pharyngeal and/or laryngeal sensibility. Regular swallowing assessments and early interventions to improve speech were recommended.

Onset of swallowing and feeding difficulties in the first two years of life occurred in late onset Pompe disease (LOPD) [84]. Szklanny et al. examined voice quality in 19 patients with LOPD, 15–57 years (47% had the juvenile form) [85]. The assessment included otolaryngological examination and electroglottographic, acoustic, and nasalance measurements. Impaired vocal fold closure and weakness of the vocal muscles caused dysphonia in LOPD and speech nasality due to insufficient closure of the soft palate. Instrumental methods revealed that the voice apparatus was most affected in patients with the juvenile form. A deterioration in voice quality was found in a follow-up study three years later [86].

ERT is an approved therapy for PD that aims to improve muscle function [87].

Myotonic dystrophy type 1 (DM1)

Hypotonia, feeding impairment and respiratory problems are early childhood features in congenital DM1 (CDM) [88]. Different aspects of orofacial function were explored in a study of children and adolescents with DM1 [89]. A majority had moderate or severe impairment of lip motility, tongue motility and lip force. Oral motor function was most affected in CDM. Parents reported problems with eating and drinking and saliva control. In an exploratory study of orofacial function, children with CDM were evaluated for speech and swallowing function and for lingual and labial strength [90]. The children had dysarthria (62%) or were non-verbal (38%). A moderate correlation was found between dysarthria, lingual strength, age, and dysphagia and between strength measures and dysphagia.

Speech characteristics, including intelligibility, speech sound production, nasality and compensatory articulation, have been investigated in patients with the congenital and childhood-onset forms of DM1 [91]. The study showed that deviant production of bilabial consonants, interdental articulation and hypernasal speech are characteristic features of dysarthria in CDM and childhood DM1 and that dysarthria is more frequent and more severe in CDM compared with childhood DM1. Based on the findings, it was concluded that most children with DM1 will need speech therapy. In case of incomprehensible speech or severe neurodevelopmental disorder, alternative and augmentative ways of communication could be a part of the treatment.

The “Consensus-based care recommendations for congenital and childhood-onset myotonic dystrophy type 1” (2019) includes recommendations for feeding concerns, dysphagia, and dysarthria [92].