Dysphagia in adult myopathies

Dysphagia (impaired swallowing) is not a rare problem in various neuromuscular disorders, both in the pediatric and the adult patient population. On many occasions such patients are first presented to other medical specialists or health professionals. Disorders of deglutition are probably underrecognized in patients with a neuromuscular disease as a result of patient's and doctor's delay. This review will focus on dysphagia in adults suffering from a myopathy. Dysphagia in myopathies usually affects the oropharyngeal phases which rely mostly on voluntary muscle activity of the mouth, pharynx and upper esophageal sphincter. Dysphagia is known to contribute to a reduction of quality of life and may also lead to increased morbidity and mortality. The review includes an overview on symptomatology and tools of assessments, and elaborates on dysphagia in specific hereditary and acquired myopathies.


Introduction
Swallowing is the process of clearing food and fluids from the oral cavity into the stomach. It is traditionally separated into three process: a. the oral phase -bolus preparation (i.e. chewing and fragmentation) and its moving toward the pharynx, involving the lips, tongue, palate and teeth. The actual moving of the prepared bolus is quick (2 s); b. the pharyngeal phase -pushing the bolus by the posterior part of the tongue toward the upper opening of the esophagus and protecting the airway system. This involves opening of the upper esophageal sphincter (UES) and closing of the vocal cords. This process is very rapid (less than 1 s); the UES, pharynx and suprahyoid muscles must act synchronously to ensure an effective swallow -UES opening occurs as a result of cricopharyngeal relaxation and laryngeal excursion due to contraction of the suprahyoid muscles [1] ; c. the esophageal phase -autonomic peristaltic movement of the bolus from the pharynx into the stomach (for more details see [2][3][4] ).
The term dysphagia is derived from the Greek words ϕαγ εῖν ( phagein ) and δυσ (dys, with difficulty). Dysphagia (impaired swallowing) is not a rare problem in various neuromuscular disorders (NMD's), both in the pediatric and the adult patient population (see Table 1 ). In several of the adult disorders it is of major clinical importance, but on many occasions such patients with NMD are first presented to other medical specialists or health professionals, such as otorhinolaryngologists, dietitians, speech therapists and sometimes psychiatrists. They either establish the diagnosis and start treatment or refer the patient to a neuromuscular expert if an association of dysphagia with a NMD is considered. Disorders of deglutition are probably underrecognized in patients with NMD and many with complaints of deglutition are not evaluated for their swallowing complaints and therefore subclinical dysphagia may be overlooked [5] .
This review aims to describe the dysphagia field to those who take care of patients with all types of NMD's, but will concentrate on the adult population and myopathic conditions. This is because we wanted to keep the review focused in the subfield where dysphagia seems to receive less attention by many clinicians. Impaired swallowing in myasthenia is well recognized and usually responds well to therapy. In neuropathies dysphagia is rare and in motor neuron diseases it requires a separate review. In patients with NMD, dysphagia is known to contribute to a reduction of quality of life and may also lead to increased morbidity and mortality. Dysphagia in neuromuscular disorders affects usually the oropharyngeal phases. These phases rely mostly on voluntary (skeletal) muscle activity of the mouth, pharynx and upper esophageal sphincter. Issues related to problems in central nervous system control of swallowing and disorders of sensation in the mouth and pharynx will not be discussed, although rarely these functions can be affected in adult NMD. Esophageal dysphagia which is caused by a variety of disorders affecting the smooth muscle of the esophagus is beyond the scope of this review.

Symptoms
Impaired swallowing can be detected by various tests before the patient becomes symptomatic.
For this review dysphagia will be defined by the presence of clinical symptomatology. Symptoms of dysphagia may appear in the early phase of myopathies or develop late through the chronic phase. The typical symptoms include: -slow eating: this is an early symptom that rarely brings the patient to the physician. It is usually detected retrospectively once more disabling symptoms appear.
-difficulty in navigating the food in the mouth due to tongue weakness. -difficulty in chewing food: this occurs mainly in conditions that affect the muscles of mastication (masseter, temporalis) and lips. -drooling or excessive sialorrhea: with weakness of the facial muscles drooling is a frequent complaint and has social implications. At times the complaint is of increased sputum production but usually the problem is of reduced 'automatic' swallowing of the normal sputum production (1-1.5 l per day). -oronasal regurgitation: this occurs when the high palate muscles are weak or fatigue easily. Usually this is associated with a change in voice and speech. -coughing or choking during eating and swallowing: this problem may be ignored initially by patients, but usually when it becomes frequent patients approach their physician. At times it may be noted by the family or social contacts of the patient. -recurrent aspirations and aspiration pneumonia: these are of course the main problems caused by dysphagia and of major health importance. Even if advanced surgical measures and insertion of a feeding tube via percutaneous endoscopic gastrostomy (PEG) are used, these cannot fully prevent recurrent aspirations and damage to the lungs which may eventually lead to death. -malnutrition and dehydration usually occur late in patients with severe dysphagia, but occasionally reduced alimentation is not given sufficient attention by the carers. When dysphagia is severe and nutrition is not restored it can lead to death.
The psychological and social aspects of dysphagia should not be forgotten. Patients avoid eating in public (including family events) and many have secondary mood changes. Depending on the type of NMD, dysphagia is frequently associated with symptoms of dysarthria, dysphonia and respiratory impairment in addition to limb weakness.

Assessment
There are numerous modes of dysphagia diagnostic and severity assessment measures. Some are bed-side, noninstrumental methods and some are relying on various types of imaging and other invasive modalities. The existence of multiple modalities and tests indicates that the field did not establish a consensus and there are no clear guidelines for testing, especially in adult NMD. Reliability, specificity and sensitivity were not well established (if at all) in most adult NMD conditions. Audag et al. [6] have analysed various studies reporting dysphagia assessment in adult NMD. Their analysis was based on an extensive literature search that identified only 19 studies suitable for evaluation of tests. All were observational in nature and at "fair" evidence level only.
It has to be noted that tests to confirm dysphagia may depend on the specific condition and the primarily affected muscles. For instance, in patients with weakness of chewing or of the tongue, tests results will be different than in patients with pharyngeal weakness. Validation of the test for an early diagnosis of dysphagia may not necessarily make it a good method for monitoring disease progression. This is especially important for assessment of therapy results (surgical, endoscopic or experimental pharmacologic).
Patient-reported outcome (PRO) tools and related questionnaires : In recent years increasing importance is given to self-assessed patients' reported symptoms as major diagnostic and research tools in numerous conditions. As a result, a plethora of such tools was developed, but not all gained wide usage. Some have not been fully validated and others were tested only for certain types of diseases causing dysphagia. Language and cultural barriers are also important in applying those tools in different patients' populations. A systematic review [7] of the many reported PRO's identified those tools which comply with most criteria to fit oropharyngeal dysphagia (SSQ and SWAL-QOL). Two other easy-to-use tools will also be mentioned because of their suitability for the non-dysphagia expert user (EAT-10 and NdSSS). These four tools will be briefly described here: -EAT10: this self-administered questionnaire is based on 10 reported topics and is simple and quick to use ( Fig. 1 ; [8] ). Its validity and reliability were shown in a study with videofluoroscopy as the gold standard of a mixed group of patients with various causes of dysphagia [9] . This tool was used in a small number of NMD's, mainly amyotrophic lateral sclerosis (ALS) patients and can adequately identify those patients at risk for penetration of food to the airway system and risk of aspiration (as confirmed by imaging).
Because it is an easy-to-use and to-quantify questionnaire (maximal score is 40 and 'no problem' score is 0, any score above 3 is abnormal) it can be applied by any physician dealing with NMD's. -Neuromuscular disease swallowing status scale (NdSSS): This is a generic dysphagia clinical scale based on eight levels of disability [10] . It is an easy-to-use scale, similar to a certain degree to the EAT-10 scale although less quantifiable. It showed satisfactory reliability, validity and responsiveness when tested in Duchenne muscular dystrophy (DMD) and ALS, despite the different rate of dysphagia progression in these two conditions. It seems more suitable for clinical staging than as a research tool. -Sidney swallow questionnaire (SSQ): This is a more detailed patient-reported outcome tool. It uses a visual analog scale for a symptomatic severity report by the patient and was validated for the normal population as well as oropharyngeally dysphagic patients [11] . Maximal severity score is 1700, with normal population score below 250. The SSQ is simple to conduct and can be performed in about 10 min [12] . -Swallowing quality of life (SWAL-QOL): This is a more detailed tool based on 44 items that report quality of life concepts, reflecting the shift from demonstrating impairment to recording disability [13] . This detailed measure is somewhat cumbersome to use for routine practice but is considered a good research tool [14] . The maximal (normal) value is 100 and lower values indicate more impairment. In oropharyngeal dysphagia various PRO's were compared and SWAL QOL was found to be one of the two strongest rating questionnaires [15] . However, the NMD's were a small group in this evaluation.
Bedside testing : there are three practical methods for testing possible dysphagia at the clinic or bed side. They are based on swallowing performance during fluid drinking: -Timed cold water drinking test: This measures the severity of dysphagia by timing the process of drinking 80 cc of cold water. This is an easy-to-administer test that was used during the gene defect search in oculopharyngeal muscular dystrophy (OPMD) [16 , 17] . It has high sensitivity for abnormality and is a very practical screening test for the presence of dysphagia. However, like numerous other swallowing tests it can give variable results in the same patient in test-retest under different situations. This practical test is also dependent on head position during the test. The upper limit value for time to complete this task in healthy normal adults is 8 s for cold water. When the fluids used are with increased consistency (nectar and honey thick) the impairment is more evident.
In OPMD patients the time to complete the water drinking test is prolonged and increases with the age of the patients. It did show a response to experimental therapy in an open label therapy trial [18] .
-Three-ounce swallow test (3SwT): This test is similar to the cold water drinking test, but is defined in a binary mode: failed or not. The subject is supposed to drink three ounces (90 cc) continuously (directly from a cup or using a straw). Failure is defined as inability to complete the task, coughing or choking during the drinking or 'wet voice' up to one minute after the test. When compared with fiber optic endoscopic evaluation of swallowing (FEES) in a variety of dysphagic conditions it showed low specificity and failure is not indicative of inability to use thin liquids in the diet or the overall status of oral feeding [19] . -Dysphagia limit (DL): defined as the volume of fluid at which a subject needs two or more swallows to complete the task. Symptomatic patients usually cannot swallow more than 20cc and this test was well correlated with the disease course in ALS, inflammatory myopathies (IIM) and myasthenia [20][21][22] .
The above-mentioned 'non instrumental' tests are quick and cost-effective in diagnosing dysphagia but their level of sensitivity and for disease status (progression) and specificity need probably to be validated for each disorder.

Instrumental (invasive) methods:
-Fiber optic endoscopic evaluation of swallowing (FEES) is used to evaluate swallow safety and efficiency. For this Fig. 1. Self-administered questionnaire to identify those patients at risk for penetration of food to the airway system and risk of aspiration [ Ref. [8] ].
evaluation, an endoscopic camera is inserted transnasally and the swallowing process is viewed looking down from the oropharynx. The expert can observe the pharyngeal phase and record the presence of food residue. This is a good diagnostic tool but hard to quantify. The results are also very dependent on the type of food used for this test. -Maximal tongue pressure (MTP) can be measured using a special pressure recording device. The patient presses the tongue toward the palate and a disposable oral balloon records the exerted pressure for 7 s. This method could be useful in conditions in which the tongue is specifically affected and its reliability was tested in few conditions (e.g. spinal bulbar muscular atrophy; [23] ). -Manometry assessing the upper esophageal sphincter is a good test for assessing esophageal dysphagia, mainly in patients with central nervous system disorders or local disease (cancer and irradiation). It was used also in ALS and spinal muscular atrophy (SMA), but is not specific to any of these conditions. -Surface EMG records noninvasively the muscle activity during swallowing. The signal is recorded by electrodes placed over the orbicularis oris, masseter, submental and infrahyoid muscles. The pattern of activation during eating is analyzed (see [24] ). While it was studied in DMD, this non-quantifiable method depends on cooperation and is of limited practical usage.
Imaging: dysphagia functional assessment by imaging can be characterized by two terms: swallowing safety and swallowing efficiency. Swallowing safety reflects the presence or absence of food or liquids with potential or observed entering into the airway system. Material entering the airway (aspiration) places an individual at risk of developing respiratory infections and choking episodes. Swallowing efficiency reflects the presence or absence of material being left in the pharynx after the swallowing attempt, or the need to take multiple swallows for a single bolus. Generally, three or more swallows for a single bolus is considered inefficient.
-Videofluoroscopic swallowing study (VFSS) is a modified barium swallowing examination. VFSS yields a dynamic xray viewing of the swallowing process. The patient takes sips of various liquids prepared with barium contrast, in order to assess safety and efficiency of bolus flow, as well as its kinetics. The volume and consistency of the barium fluid has not been strictly defined and can impact the overall results.
VFSS was validated in multiple studies, is used routinely in clinical patient evaluation and is considered a 'gold standard' for dysphagia assessment. It reflects accurately the risk of pneumonia and aspiration and has high correlation with SWAL-QOL in dysphagic patients, but information about NMD's follow up is scarce.
The observed findings during VFSS can be assessed by a scale called penetration-aspiration (PAS). Penetration is defined as material entering the airway above the level of the vocal folds. Aspiration is defined as material falling below the level of the vocal folds. This 8-level scale describes the depth of penetration or aspiration, and whether or not the material was ejected. Levels 1-2 are considered "normal/safe/functional", while levels 3 or more describe penetration or aspiration events that place an individual at risk for negative sequelae, such as aspiration pneumonia. It is not uncommon for this scale to be used in a binary manner to group safe versus unsafe (i.e., 1-2 = safe, 3 or more = unsafe). The scale is semi-quantitative in nature, and should be assessed by an experienced person. Another mode of dysphagia assessment based both on clinical data and VFSS called dysphagia outcome severity scale (DOSS) was developed. The idea is to combine clinical features with imaging. This logical approach also has limitations, as the reliability of the tool is dependent on the experience of the experts using it [25] .
With additional imaging analysis programs, the kinetics of the various step of the rapid swallowing can be timed (e.g. in OPMD; [26] ).
-Oropharyngeal esophageal scintigraphy (OPES). Radionuclide esophageal transit time mimics the water drinking test. The patient drinks 10-20 cc of water mixed with a small amount of Technetium 99 monitored by isotope camera. The radioactive signal usually disappears from the pharynx within 3 s in normal people and this clearance is much delayed in OPMD [27] . This test records the bolus movement (and residues) rather than the swallowing physiology. Recently, Barsotti et al. [28] finetuned this test which allowed for assessing the transit time (TT) and the retention index (RI) at oral, pharyngeal, and esophageal level. The study was performed on patients with idiopathic inflammatory myopathies (IIM) and not only included the liquid test but also a repeat test with a semisolid bolus of 99m Tc administered 30 min after excluding tracheobronchial aspiration by the first evaluation. At the end of the second procedure to assess esophageal dysmotility the patient was asked to swallow using a straw 6 times, 5 cc of water with 99m Tc for 3 min. The authors recommend OPES because it is a simple technique, repeatable, non-invasive and well-tolerated. There is exposure to only a low-dose of ionizing radiation.
-Real time MRI during swallowing of a paramagnetic fluid (pineapple juice with yeast thickening) was studied in patients with inclusion body myositis (IBM) as a possible technique with similar capabilities to detect dysphagia compared with VFSS [29] . Its advantage is visualization of the soft tissues and lack of exposure to X-rays. However, it awaits further data to show any superiority compared with 'classical' methods.
In conclusion, the various instrumental tests mentioned above are representing a 'snapshot' of the swallowing during the test. They do not inform on fatigability of the process with repeat swallowing during normal eating. Such fatigability is probably relevant to numerous NMD's. Most of the tests depend on the characteristics of the swallowed material used. Thus, numerous factors need to be controlled when using them as outcome measures for studies of dysphagia in NMD.

Management and treatment of dysphagia
Treatments of dysphagia range from behavioral exercises to end stage PEG insertion. None of the various treatments that will be described was evaluated by a long term controlled and randomized study (see [30] for Cochrane analysis). Since in NMD's dysphagia is progressive, some of the prescribed treatment modes may have only temporary relief.
Changing of diet and eating habits: many patients modify their diet to the perceived difficulty they have. Many OPMD patients for instance add frequent water sips to the swallowing of food. In other conditions people may prefer semisolid food, especially if the oral phase is mostly affected. Studies on increasing bolus viscosity were evaluated for their efficacy and safety [31] . The main observations were: increased viscosity made swallowing safer but resulted in more residue which can in turn be a risk for later aspiration. It was associated with increased risk of dehydration and the palatability of the food was negatively affected. The conclusion from these studies is positive value of thickened food on swallowing physiology at the expense of several negative effects. Postural changes during eating may change the swallowing process, especially the head position. For instance, chin-up, a slight backward tilt, is practiced by many patients with dysphagia. A study of the chin-up posture has shown increased impact on the pharyngeal phase in normal and dysphagic patients after neck cancer treatments [32] . Many of the various modes of such 'behavioral' treatments were not scientifically evaluated by any controlled study but their usage by many speech therapists indicates that there may be a beneficial effect to such training.
Non-pharmacological interventional therapy -Dilatation of the upper part of the esophagus (UES): This procedure should be done by an experienced person. The idea is to relieve the functional narrowing of the UES using a dilating bougie. This intervention has an effect that usually lasts few months to very few years and its long-term effects have not been systematically studied. It can be repeated (in some cases it was done more than 10 times [33] ), but the risk of complications (mainly tear of muscles) increases. -Cricopharyngeal myotomy: dysphagia caused by numerous conditions, including NMD's, affects several muscles of the pharynx. However, the major functional obstacle is mostly due to the impaired function of the cricopharyngeus muscle, which is the main muscle of the UES. There are several techniques for this procedure which results in partial to complete inactivation of the UES. The clinical effect of myotomy is relatively rapid, but its long-term efficacy depends on the nature of disorder it is used for. Progressive weakness of the other muscles involved in the oropharyngeal swallowing will reduce its long-term improvement. A repeat surgery may at times be performed, mainly to eliminate the effect of fibrous tissue replacement in the cricopharyngeal muscle. -Percutaneous Endoscopic Gastroscopy (PEG): This procedure is in use for four decades in the treatment of chronic dysphagia disorders. Insertion of feeding tube via PEG ensures (home) enteral nutrition and hydration and is considered as an easy surgical procedure. If endoscopically guided tube placement cannot be performed, RIG (Radiologically Inserted Gastrostomy) or PIG (Per-oral Image-Guided Gastrostomy) is an alternative technique [34] . Home enteral nutrition does not only increase survival but improves quality of life and feeding can be done by non-medically trained persons, e.g. carers. One should remember that aspiration of gastric content or oral secretions is not prevented by PEG mode of therapy. Although used in several NMD's, surprisingly an evidence-based guideline about home enteral nutrition only mentions 'swallowing disorders because of neurological disorders' [34] and a review about PEG [35] mentions only ALS as an indication.
Inserting PEG and even more so withdrawing a feeding tube is associated with major ethical issues. Nutrition by artificial means is considered medical treatment requiring an indication for achieving a treatment goal, i.e. to prevent malnutrition/undernourishment and to improve quality of life. The patient has the right to participate in all the decisionmaking concerning his treatment.
Most of the literature on ethical issues with regard to insertion of PEG pertains to ALS. Discussing gastrostomy in patients with ALS when swallowing difficulty emerges is considered good clinical practice [36] and a recently published guideline [37] recommends to discuss gastrostomy at an early stage and at regular intervals, taking into account the patient's preferences and wishes. These conversations are part of what is called advance care planning (ACP) and this is not necessarily restricted to the end of life. Not only the need for gastrostomy (weight loss, effort of feeding and drinking and risk of choking) should be discussed, the patient's quality of life should also be addressed and measured. Possible complications of the tube placement and the possibility to discontinue artificial nutrition and hydration should be clearly communicated as well.
It is important to appreciate that there may be cultural, religious and legal differences related to the use of 'artificial' feeding. Gradually there is increasing awareness that ACP is also appropriate in advanced stages of other neuromuscular diseases such as myotonic dystrophy, inclusion body myositis. Those diseases are chronic progressive, associated with incapacitating disability and in myotonic dystrophy with a shortened life expectancy (De Die-Smulders 1999). PEG may be withdrawn at the request of the patient when the burden of the intervention outweighs the patient's quality of life, but there is no literature on that as regards NMD's. In 2016, the ESPEN Guideline on Ethical Aspects of Artificial Nutrition and Hydration discussed the indications for artificial nutrition and also the ethical issues with regard to withdrawal or withholding this treatment [38] . The decision to discontinue enteral feeding is a unique journey for every patient and their families and should be communicated properly. It is the duty of the health care professionals to adequately manage the symptoms of dysphagia when the tube has been removed.
-Botulinum toxin injection: This mode of non-invasive therapy is used mainly when the functional swallowing impairment creates relative overactivity of the UES. However it was not systematically evaluated in well controlled studies [39] and showed some inferiority when compared with the more invasive myotomy and even dilation [40] . Its usage for dysphagia in NMD's seems less logic since it weakens the pharyngeal musculature, however this procedure was infrequently applied in such conditions. The risk of increasing weakness of the cricopharyngeal muscle and the rare possibility of affecting other close by muscles needs to be strictly assessed before this method becomes an endorsed management procedure for NMD's.
Experimental therapies of dysphagia were studied mainly in OPMD and will be discussed below.
Logemann et al. [41] point out that oral health and thus a dentist should play an important role in the management of patients with dysphagia. The status of dentition allowing a successful chew should be regularly checked. Oral hygiene also prevents halitosis which may lead to personal discomfort and social embarrassment. Finally, there are indications that poor oral health may be a risk factor for aspiration pneumonia albeit this has not been investigated in patients with neuromuscular disorders.

Oculopharyngeal muscular dystrophy (OPMD) : OPMD
is the prototypic adult-onset hereditary myopathy that has dysphagia as a major symptom. There are three large clusters of patients with high prevalence of this dominant disorder (French Canadians, Bukhara Jews and Hispanic in the USA). As a result, despite being a rare condition, there is relatively a large 'bank of data' about dysphagia symptoms, assessment, and management (including therapy trials) in this condition.
The median age of onset of dysphagia in this disorder was determined in a retrospective study of 333 patients in Quebec to be 53-54 years [42 , 43] . In 32% this was the first symptom and in an additional 9% it was ptosis and dysphagia.
A panel of experts reviewed the most frequent symptoms and assessed their effect on patients' life [44] . Of the list of 24 reported symptoms, swallowing difficulty mainly to solid food, a sense of throat blockade and coughing and choking during eating were considered to be the most problematic. The effects of all these symptoms were on eating habits (e.g. small bites) and prolongation of eating time [14 , 42 , 44] . Eating fatigue, a less commented-upon symptom in the past, received new attention.
The progressive nature of the dysphagia in OPMD led to therapeutic interventions within a mean of eight years from onset. Aspiration pneumonia became evident around a mean age of 73 years and those patients reaching the stage of need for PEG feeding tube, the time from disease onset averaged 18 years [43] . In 31% of death causes of OPMD patients it was due to respiratory problems.
Various modes of dysphagia assessment were used in OPMD. SWAL QOL was the best validated tool, however it had some weakness in a comparative study [14 , 44] . The main VFSS features of dysphagia were studied in 22 patients [42] . The vast majority had, as expected, pharyngeal dysphagia and half of them had cricopharyngeal 'bar'. When breaking the observations into more functional aspect, 51% had inefficient although safe swallowing, 32% had both inefficient and unsafe swallowing and the rest had both safe and efficient swallow test. In a more detailed kinematic VFSS assessment in 11 patients who participated in a drug trial [26] the most significant impairments were those of pharyngeal constriction, hyoid movement and timeliness airway closure, indicating a muscle malfunction.
Several treatments of dysphagia were specifically reported in OPMD. Results of pharyngeal dilatation were followed in nine patients [33] . Most patients had several repeated dilatations (mean seven per patient) with a mean interval of 15 months. Follow up showed reduced SSQ score by 73% as a result of this procedure. Extramuscular cricopharyngeal myotomy resulted in short term improvement in most patients, but about one third had to go through another surgical myotomy procedure within about four years [45] . Interestingly, a recent study of coping strategies toward dysphagia showed negative patients' attitude toward surgery [46] . Botulinum injection into the cricopharyngeus muscle, mostly percutaneous with EMG monitoring, was associated with subjective improvement in 60% of OPMD patients, but many injections (most patients received more than one) had adverse effects of dysphonia and transient dysphagic aggravation [47] .
Two preliminary results of therapy trials in OPMD were reported. Autologous myoblast transplantation into the cricopharyngeus muscle during myotomy was studied in 12 patients [48] . It showed cell dose-related reduction in cold water drinking test and improved quality of life as a result of the combined procedure. Weekly IV trehalose infusion over 24 weeks in an open label study led to significantly improved cold water drinking test [18] .

Oculopharyngeodistal myopathy (OPDM) : This condition
was first noted to be different from OPMD in few Japanese patients [49] .The main features of ocular involvement, swallowing difficulties and skeletal muscle weakness seem to resemble OPMD, however there are some clinical features that separate them: in OPDM ophthalmoplegia is a frequent early sign, facial muscle weakness and masseter atrophy are prominent and the weakness starts distally [50 , 51] . Two modes of inheritance were recorded: the more frequent is dominant but few pedigrees had recessive inheritance mode [52] . The genetic defect in the dominant form was recently identified [53] : a CGG repeat expansion in the LRP12 (low-density lipoprotein-related protein 12) gene.
Dysphagia is clearly a major sign of OPDM as its name implies. However, there are only descriptive swallowing difficulty observations in this condition. It usually appears in patients who had the first sign (ptosis) for more than 5 years, although in few it was the first symptom. The dysphagia is more evident for liquids and is associated with hoarse and nasal voice [50] . Three patients in this series did not benefit from myotomy. Now that a genetic diagnosis is available, a more detailed study of the dysphagia in this syndrome can be performed. It is expected to be of mixed oral and pharyngeal disturbance and thus may differ from OPMD.

Myotonic dystrophy (DM): impaired eating and swallowing
is a common problem in DM especially when the disease progresses. The main observations about dysphagia were made in DM1 [54 , 55] , the more prevalent and severe form of myotonic disorder in adults. The prevalence of dysphagia in DM1 is reported to be 25-80%, depending on disease duration and severity. The degree of dysphagia ranges from mild (about half of the patients) to severe (about 20%). When SWAL-QOL questionnaire was administered to 75 DM1 patients low scores were found in all domains [56] . This clear subjective report did not, however, correlate with the VFS findings in a subgroup of this study. Furthermore, although presymptomatic subjects carrying the DM1 mutation did not complain about dysphagia even when a PRO was administered, most have shown abnormality in a FEES study [55] .
The type of dysphagia in DM1 is mixed and involves all phases. It should be pointed out that smooth muscle involvement in DM1 affects also the esophagus and contributes to impaired overall swallowing as shown by manometry and VFS [57] , but gastrointestinal affliction in DM1 is beyond the scope of this review. This is not surprising as in this disorder there is weakness of facial, palatal, pharyngeal and esophageal muscles. An EMG study suggested that myotonia of masticatory muscles contributed to the swallowing impairment (Ertekin quoted in [54] ). A review of oropharyngeal dysphagia in DM1 identified 16 studies using validated tests [54] . This review did not detail the esophageal impairment observations. It is clear that there was no uniformity of the tests used in DM1 patients, however FEES and manometry were the more frequently applied. The main features of oropharyngeal dysphagia in DM1 included pharyngeal pooling, decreased pharyngeal contraction with delayed pharyngeal reflex and reduced UES resting tone. The degree of impairment in the imaging studies and the amount of residue was dependent on the type of bolus used, more thick liquid was associated with more frequent abnormality.
Although this review is limited to dysphagia in adults with myopathies, it should be noted that in congenital DM1 swallowing problems are more prominent [58] .
In DM2, where symptoms appear later in life and are considered to be less severe than those of DM1, dysphagia can occur. It is usually milder and not associated with aspiration and weight loss, however FEES was abnormal in most patients who reported swallowing difficulty and the DOSS (Dysphagia Outcome and Severity Score) was correlated with patients' age [59] .
Recently published consensus-care recommendations on DM1 and DM2 [60 , 61] provide general recommendations, including nutritional supplement and dysphagia therapy referral, including compensatory strategies and dietary modifications.

Facioscapulohumeral dystrophy (FSHD): Facial weakness
is one of the main features of this dominantly-inherited condition. It is expected that weakness of lips and cheeks will affect food bolus preparation and impair swallowing. Most FSHD patients do not complain about dysphagia, however when SWAL-QOL is administered around a quarter report symptoms including increased eating duration and fear of choking [62] . There seems to be an effect of fatigue in their dysphagia.
A subgroup of FSHD patients has tongue weakness, despite the fact that this was considered an exclusion clinical criterion for this diagnosis in the past. Seven of 151 Japanese patients had tongue atrophy when studied by MRI [63] . Testing tongue power also showed reduction in a group of 43 patients [62] . When VFSS (or barium cineradiography) was used in small selected group of patients, abnormalities were found in 6/8 [64] or 5/20 [5] patients. These studies concluded that in FSHD mild to moderate dysphagia occurs, especially in those with early onset or tongue atrophy.

Mitochondrial myopathies
Primary mitochondrial disorders (MIDs) are genetic conditions that impair various metabolic processes of these organelles (primarily but not solely oxidative metabolism). The clinical spectrum of this group of disorders is broad and usually affects multiple systems. Finsterer and Frank [65] performed a systematic review on gastro-intestinal involvement in mitochondrial disorders and found that dysphagia was reported in all types of MIDs including mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS), myoclonic epilepsy with ragged red fibers (MERRF), chronic progressive external ophthalmoplegia (CPEO), Kearns-Sayre syndrome, mitochondrial neurogastrointestinal encephalomyopathy (MNGIE), Leigh Syndrome (LS), and sensory ataxic neuropathy, dysarthria and ophthalmoparesis (SANDO). The review did not address diagnostic measures, but did briefly discuss management. Treatment of dysphagia was usually symptomatic, i.e. dietary measures, tube feeding or insertion of a PEG. In MNGIE therapy with bone marrow transplantation can restore thymidine phosphorylase enzyme function [66] . Despite a substantial transplant-related mortality, the patients who were engrafted and living more than 2 years after transplantation showed improvement of body mass index, gastrointestinal manifestations, and peripheral neuropathy. Recovery of the gastrointestinal symptoms and in particular weight gain took a long time and was often partial.
Patients with CPEO due to single large-deletions were screened for dysphagia by the cold-water test and a standardized questionnaire about dysphagia [67] . The authors found progression of dysphagia with age. Fourteen patients with CPEO caused by mtDNA deletion(s) or point mutations were subjected to videofluoroscopy to evaluate the pharyngeal transit of liquid, paste and solid boluses after they were carefully investigated by a speech-language pathologist [68] . Functional evaluation was performed with swallowing 5 mL and free volumes of liquid, paste and solid boluses. Nine out of 14 patients had swallowing difficulty mainly related to solid and dry foods, complaining about food stuck in the pharynx or choking during swallows and five were asymptomatic. More than 70% had residues in the oral cavity and almost 60% in the pharynx. A few patients had laryngeal penetration probably due to the latter.
A study on the presence of gastrointestinal problems and dysphagia evaluated by questionnaires in 92 MELAS patients, carriers of the m.3243A > G mutation, found that 45% had mild dysphagia, especially with solid food [69] .
Mutations in the mtDNA maintenance gene RNASEH1, encoding ribonuclease H1 (RNase H1), have recently been linked to adult-onset PEO and often CNS involvement, i.e. cerebellar ataxia, associated with multiple DNA deletions. Dysphagia was found in half of the 14 patients [70] .
A paper on 'Patient care standards for primary mitochondrial disease: a consensus statement from the Mitochondrial Medicine Society' provided sparse information on evaluation and management of swallowing dysfunction [71] . Recently, a workshop on outcome measures in following patients with mitochondrial disorders suggested that a clinical or bedside swallow assessment should be the first step in identifying whether dysphagia is present [72] . The workshop participants also agreed that clinical assessment can be improved, if considered safe, by using a 100 ml water swallow test (WST) and the test of masticating and swallowing solids (TOMASS), another validated and reliable quantitative assessment of a solid bolus [73] could be applied.

Duchenne muscular dystrophy (DMD)
As a consequence of better management of scoliosis, respiratory insufficiency and cardiac complications, patients with DMD live much longer [74] and new clinical issues emerge which did not occur or were not recognized previously. Van der Engel-Hoek et al. [75] described that increased tongue thickness is already present in the early non-ambulatory stages and complicates the oral phase of swallowing. In an ultrasound examination they showed that there was a correlation between increased echo-intensity of the superior longitudinal tongue muscle indicating dystrophic changes, and tongue thickness.
Videofluoroscopy showed piecemeal deglutition (i.e., the need for multiple swallows to clear the oral cavity) across the different age categories (ranging from 6 to 41 years) and functional stages, but mainly in the late non-ambulatory stage.
Delayed oral phase problems during swallowing and pharyngeal post-swallow residue, more with solid food were mainly observed in the late stages and ascribed to reduced strength of the dystrophic tongue.
A prospective study investigated and defined the nature of the dysphagic symptoms experienced by wheelchair-bound DMD patients with a mean age of 21.7 (4.2) years by using the SSQ. It was found that SSQ had a sensitivity of 0.78 and a specificity of 0.83 for determining dysphagia in the DMD participants [24] . The patients reported significant difficulty with swallowing hard foods, thick liquids and the need to cough up during meals which could all be attributed to pharyngeal weakness. These complaints had a marked impact on enjoyment and quality of life. There was a relatively low score for coughing/choking on fluids, which may indicate that aspiration of fluids is not a prominent phenomenon [24] . VFSS was performed on 19 DMD patients in different functional stages and ranging in age from 6 to 31 years who were referred for a feeding assessment by a speech and language therapist (SLT) [76] . Approximately half of them had macroglossia and pharyngeal swallowing difficulties were noted on SLT assessment. VFSS demonstrated that the pharyngeal phase is weak with incomplete pharyngeal clearance leading to a residue increasing in volume with age. The authors postulated that incomplete clearance in combination with less efficient chewing may result in choking. Airway aspiration was not observed [76] . The authors did not see much added value of VFSS in the diagnostic assessment of DMD patients with suspected dysphagia [76] . Mastication difficulty contributes to the pharyngeal residue as was shown in a case-control study of 23 DMD patients ranging in age from 6 to 38 years [77] . The patients had to fill out a questionnaire, underwent a clinical exam of the masticatory system and were subjected to ultrasound examination of the tongue. In thirteen patients (57%) mastication difficulties were reported, already at an early stage of the disease but increasing with disease severity. Prolonged meal-time ( > 30 min.) was reported by patients, parents or caretakers in 15 patients (65%), choking by 14 patients (61%) and the feeling of food sticking in the throat by 15 patients (65%). Malocclusion which can be ascribed to weakness of the facial, masticatory and tongue muscles was found in all patients and the maximum bite force was significantly weaker as compared to healthy controls [77] .
In general, it seems that administering SSQ to assess the presence of dysphagia suffices in DMD [12] and that, VFSS adds little practical information [70] . In case of choking VFSS may distinguish between supraglottic penetration and subglottic aspiration. Because of the risk of aspiration, these examinations must take place in a specialised unit where effective cough assistance techniques are available. In the recently revised care considerations on DMD, Birnkrant et al. [78] are less cautious and recommend that VFSS should be part of the assessment of dysphagia based on a paper by Hanayama et al. [79] who found abnormalities on VFSS in 90% of the cases [78 , 79] . Multidisciplinary management of nutritional care and assessment of dysphagia is key in late DMD patients. Toussaint et al. [12] developed a decision-making-tree algorithm to manage dysphagia in late ambulatory DMD patients. Avoidance of solid food and use of fluids and purees should be promoted. Additional sips of water are appropriate to clear the pharyngeal postswallow residue. In the case of aspiration, oral food should be discouraged and PEG placement considered. Other indications for gastrostomy tube placement include malnutrition that is unresponsive to interventions to improve oral caloric intake, diagnosis of moderate or severe dysphagia, and inability to maintain adequate hydration [78] .
Interestingly, a small study on seven DMD patients showed that if the patient is tracheotomized, swallowing may improve and this contradicts what traditionally is believed [80] .

Becker muscular dystrophy (BMD)
Similar to DMD, orofacial weakness leading to masticatory impairment and swallowing difficulty was described in BMD [81 , 82] . Lagarde et al. [82] reviewed charts of 11 ambulatory DMD patients (7.7 ± 1.7 years) and 11 BMD patients (10.7 ± 2.4 years) for data on SLT assessment, thickness and echogenicity of the orofacial muscles, maximum bite force. They found that BMD patients had equally affected orofacial muscles although they had a better 6-minute walking test compared to DMD patients. The question why BMD patients have early involvement of masticatory muscles remains as yet unsolved.
A comparison of videofluorography on 18 patients with BMD (45.6 ± 15.0 years) and a similar number of DMD patients (17.1 ± 3.7 years) showed that BMD patients had similar swallowing difficulty when matched according to physical functional status [81] .

Limb girdle muscular dystrophy
One would expect given the similarities between DMD and limb girdle muscular dystrophy (LGMD) caused by mutations in the sarcoglycan genes that dysphagia would occur as frequently as in DMD. However, there is only sparse data available. It might well be the result of less attention for involvement of the bulbar muscles in LGMD. An evidence-based guideline [83] on the diagnosis and treatment of LGMD's reports that no dysphagia was found in patients with LGMDR1-calpain3-related, LGMDR2-dysferlin-related, or LGMD caused by mutation in sarcoglycan genes, albeit macroglossia was found to be common in LGMDR5-γsarcoglycan-related, and LGMDR9-FKRP-related. There is one case report [84] on a patient with LGMDR2-dysferlinrelated, at that time designated as LGMD2B. In her thirties, she developed relatively rapid progressive proximal muscle weakness of the legs associated with difficulty swallowing solid food and subsequently liquids. Dysphagia worsened, with occasional penetration of liquids and she experienced intermittent nasal regurgitation of solids and liquids causing recurrent respiratory infections. Videofluoroscopy supported involvement of the oropharyngeal and upper esophageal skeletal musculature. Compensatory strategies from speech and language therapy led to marked improvement. In dominantly inherited LGMD caused by DNAJB6 mutation three cases (out of twelve) who also had dysphagia were described. Since these patients were wheelchairbound swallowing difficulty seems to be associated with advanced disease [85] . In another subtype of dominant LGMD which is due to a mutation in the termination codon of transportin 3 (TNPO3) gene dysphagia is found in 30% of the cases [86] . Interestingly, dysphagia may be transient [87] .
From our experience, clinical dysphagia is a very rare feature of autosomal recessive LGMD, even in advanced stages.

Pompe's disease
This review is about dysphagia in adult patients. However, as with DMD better treatment in Pompe's disease that became available in 2006 leads to long-term survivors. Therefore, we also discuss the sparse literature that has been published so far on dysphagia in follow-up studies of patients with infantile onset Pompe's disease (IOPD) who started on enzyme replacement therapy (ERT) with recombinant human acid α-glucosidase (rhGAA). It is possible that as survival is prolonged dysphagia will become a more prevalent problem in these patients.
An Italian study [88] followed 28 patients of whom 17 were still alive after they had been on ERT for a median of 71 months (range 25-134 months). Nine of them, ranging in age from 2.5 to 11.5 years had autonomous feeding capacities, including two who were on artificial ventilation. Nine patients (ranging in age from 4 to 11.5 years) had a gastrostomy and one (2.5 years) had a nasogastric tube.
Another study [89] found the following in 11 longterm survivors (median 8.0 years (5.4-12.0): 7/11 patients had an exclusively oral (PO) mode of nutrition intake, four used a combination of PO and gastrostomy tube feeds, and five patients had dysphagia with aspiration on videofluoroscopic swallow examination. It is of note that the swallowing function was variable in children of more or less the same age: a 12-year-old and a 10-year-old child were able to feed autonomously whereas the five suffering from dysphagia with aspiration on VFSS were between 5.6 and 10.2 years of age. A Dutch study [90] showed that swallowing was generally weak and ineffective and FEES revealed velopharyngeal incompetence and reduced muscular contraction of the pharynx leading to pharyngeal residues of food with penetration in three out of six patients. The patients were found to use no protective reflexes such as coughing or swallowing to try to clear the food. It is noteworthy that during ERT nasogastric tube (NGT) feeding could be discontinued in three out of eight patients who needed NGT right from the start. At the end of the study, five patients in age ranges from 2 to 12 years were completely orally fed. Still, four of these patients showed some signs of dysphagia, necessitating regular swallowing assessments by speech and language therapists and a safe feeding plan.
In late onset Pompe's disease (LOPD), tongue weakness, usually mild, was found in 19 adults, including two asymptomatic patients [91] . One third of them had dysphagia. The authors describe the 'methodology' as follows: 'Patients were instructed to push laterally with their tongue against their inner cheek bilaterally. The examiner simultaneously opposed with his opposite thumb and attempted to overcome the patient's lingual force while bracing with the opposite hand on top of the patient's head. Lingual strength was assessed to be normal or abnormal; if abnormal, severity of weakness was determined to be mild, moderate, or severe.' [91]. The same group later provided quantitative data demonstrating lingual weakness in 80% of 30 LOPD patients and in 42% weakness was severe [92] . In this study only dysarthria and not dysphagia was assessed. Hobson-Webb et al. [93] found dysphagia, lingual weakness and associated videofluoroscopic abnormalities in three out of 12 LOPD patients and stressed the importance of regular screening of the bulbar muscles in this condition. Carlier et al. [94] reported a bright signal in the tongue on T1-weighted MRI images of LOPD patients. Others [95 , 96] confirmed this finding and Karam et al. [96] found that it was also present in patients without dysphagia. They systematically reviewed brain MRIs of various disease groups and observed that the 'bright tongue sign' was present in three out of six LOPD patients, in two out of eight bulbar-onset ALS patients, in one out of four patients with myotonic dystrophy type 1 (DM1), and absent in patients with IBM and OPMD. Only one of the three LOPD patients with a bright tongue sign had dysphagia. In another patient there was also tongue atrophy and weakness which was much more frequently found in ALS patients (four out of eight).
According to a guideline on management of LOPD, general medical care recommendations also include optimizing nutritional status and other behavioral therapies such as thickeners and exercise [97] .

Idiopathic inflammatory myopathies (IIM)
The current classification includes dermatomyositis (DM). immune mediated necrotizing myopathies (IMNM), overlap myositis (OM), antisynthetase syndrome (ASS), and inclusion body myositis (IBM) [98] . Based on the presence of myositis associated or specific antibodies there are numerous subtypes but this is beyond the scope of this review. We will confine ourselves to the broad categories of IIM. Dysphagia in IIM is the result of inflammation of the swallowing muscles leading to impairment of the oral, pharyngeal or esophageal phase.
Dysphagia occurs in all myositis subtypes, not uncommonly as presenting symptom, mainly in IBM (4.4-14% [99] ), but also in IMNM with and without immune checkpoint inhibitor (ICI) exposure [100] , and rarely in OM [101] . In a single case of anti-Jo1 myositis, dysphagia necessitating placement of a PEG was the sole manifestation [102] . Patients in whom dysphagia was the initial symptom had a longer time to diagnosis as compared to patients with a more diffuse presentation [100] . A recently published systematic review and meta-analysis comprising 109 studies including 10,382 subjects showed an overall estimate of dysphagia prevalence of 36% in IIM [101] . In IBM patients, a prevalence of 56% was estimated [101] . Most IIM patients first report difficulty with solids, and later also with liquids, albeit one study found that dysphagia with liquid boluses occurred more frequently than previously reported [1] . Numerous studies show that dysphagia often goes unnoticed and is only demonstrated by imaging, but swallowing difficulty may also not be reported unless specifically asked about [103] .
In IIM, dysphagia negatively affects quality of life, but is also associated with increased morbidity (i.e., dehydration, malnutrition and aspiration pneumonia) and increased mortality, probably due to aspiration pneumonia which is significantly more prevalent in dysphagic as compared to non-dysphagic patients, and especially in IBM [99 , 101 , 104] . It is noteworthy that a survey amongst 510 IIM patients (IBM excluded) and 101 health care professionals (HCPs), dysphagia was ranked much higher by HCPs as compared to patients implying that this symptom will not enter the top domains of the core set of PROs [105] .
Unfortunately, the meta-analysis by Labeit et al. [101] only distinguishes DM, PM and IBM, whereas we currently know that IIM without skin development ('PM') can be differentiated in OM, IMNM and also a proportion of ASS patients.
There is only sparse literature on non-invasive assessment methods to identify the causes of swallowing difficulty in IIM patients. Recently Barsotti et al. finetuned a test -oropharyngo-esophageal scintigraphy (OPES) -that was used in OPMD patients and conducted a study on IIM patients. Fifty-one patients (DM, PM -defined by Bohan and Peter criteria [106] -and IBM) were first subjected to PROs (EAT-10 and the MD Anderson Dysphagia Inventory (MDADI)), and were found to have dysphagia in 49% and 59%, respectively. The OPES showed at least one abnormality in every patient and found a higher frequency of abnormalities with the semisolid as compared with the liquid bolus. The majority of patients had swallowing dysfunction during the oral phase and esophageal abnormalities were associated with a longer disease duration. OPES and in particular the test with the semisolid bolus also detected tracheobronchial inhalation in three asymptomatic patients. Both at baseline and at 6 months follow up there was a correlation between the MDADI score and several OPES parameters both for liquid and semisolid swallowing and in particular at pharyngeal level. Whereas this is a valuable study there are also flaws regarding the methodology. All patients without skin features were lumped together into the group of polymyositis defined by the Bohan and Peter criteria which are by now considered outdated [107 , 108] . Besides, the authors only included 2 IBM patients. The MDADI was used as primary tool which was validated in patients with dysphagia due to head and neck cancer.
Olthoff et al. performed real-time MRI on patients with IBM [29] and found bolus retention as the major abnormality in 15 out of 20 patients with IBM and this was associated with a significantly prolonged pharyngeal transfer time . The authors compared real-time MRI with VFSS and FEES and found that MRI was non-inferior to the other techniques.
Langdon et al. [1] performed combined manometry and VFSS in 18 patients with IIM (of whom 12 had IBM) and found that the dysphagia was consistent with pharyngeal and suprahyoid muscle weakness rather than failed UES relaxation. Another study [109] performed a retrospective review of VFSS on 23 IIM patients (7 had IBM and 13 DM) and found that patients with myositis had a significantly shorter duration of UES opening and laryngeal vestibule closure than healthy subjects. The authors hypothesize that this might be caused by poor endurance in the suprahyoid musculature of the IIM patients. The results of these studies have consequences for therapy. However, both studies suffer from relatively small sample sizes.
There are manifold therapeutic regimens, including numerous immunosuppressants or immunomodulation modalities aimed at ameliorating muscle weakness including dysphagia. However, there is no evidence base for that, since a Cochrane review did not address dysphagia as a separate outcome measure [110] . Furthermore, as IBM does not respond to these pharmacological interventions dysphagia therapy remains of major concern as this condition progresses.
In order to properly assess the outcome of invasive therapies, like botulinum toxin, cricopharyngeus dilatation or myotomy, it is crucial to determine the mechanism of dysphagia. In particular, there is uncertainty about the role of the UES in the swallowing process, suggesting that the suprahyoid musculature shows weakness or reduced endurance rather than failed UES relaxation.
All three above-mentioned interventions have been performed in IIM with varying results as regards improvement of the swallowing function and the duration of the symptom relief, which perhaps is not surprising since most interventions take place without thorough evaluation of the cause of dysphagia. Even more concerning is the fact that there are no interventional trials with meaningful clinical endpoints [101] . This also holds true for behavioral swallowing therapies [101] .
Given the paradigm shift as regards the role of the cricopharyngeus muscle exercise therapy rather than mechanical disruption of the cricopharyngeus muscle has been suggested [109 , 111] . A pilot study using a device (the Expiratory Muscle Strength Trainer) to strengthen the suprahyoid musculature showed feasibility but failed to show improvement of the swallowing function which may be due to underpowering.

Miscellaneous conditions
Some patients with congenital myopathies and relatively benign course survive into adulthood and may have dysphagia. Usually there are no specific details about this late feature but in some of these very rare disorders there are more reported details [112] .
Dysphagia has been reported in adult myofibrillar myopathies MFM caused by mutation in the desmin gene and αB-Crystallin gene and rarely in Emery-Dreifuss muscular dystrophy/scapuloperoneal myopathy caused by four-and-onehalf LIM1 protein (FHL1) defects [113] . No data is available about assessment and management. Similarly adult onset myopathy due to CRYAB defect (one of the myofibrillar myopathies group) may also feature weakness of pharynx and the soft palate with swallowing difficulties [114] .
A rigid spine syndrome with vacuolar changes in muscle fibers presents with myopathy in early childhood (before age 6 years). The exact genetic defect is unclear but few reported patients are sibs. Some complain about swallowing difficulties and nine patients were studied by manometry [5] , which revealed only mild esophageal impairment.
In the severe infantile onset X-linked myopathy (XLMTM), dysphagia is part of the life-threatening condition in boys. Interestingly, a female carrier with mild myopathy belonging to a pedigree with the infantile form had a milder condition and at adulthood reported dysphagia. VFS demonstrated the impaired laryngeal movements [115] .
Distal myopathy with vocal cord involvement (VCPDM) is an adult onset autosomal dominant disorder due to defects in the MATR3 gene [116] . Pharyngeal weakness accompanying the vocal cord dysfunction may be part of the presenting clinical picture, between the 4th-6th decade [117] . The disorder is slowly progressive and patients may need interventions but no formal studies were performed.
Late adult onset nemaline myopathy with or without monoclonal gammopathy is a rare condition which may have a genetic basis (e.g. RYR1 mutation). In 4% of a cohort of such patients dysphagia was an initial symptom and about half of the patients developed swallowing impairment during the course of the disease [118] .

Conclusions
This review shows that swallowing impairment frequently occurs in adults with myopathies, but is often not recognized either by the patient or by the physician who is not always aware of this complication. The underrecognition of swallowing impairment may lead to a reduced quality of life, to increased morbidity in terms of weight loss or aspiration and in some diseases, there may be an association with mortality (the main ones are OPMD, DM1, adults with DMD and IBM). In these conditions surgical interventions seem currently to be the best mode of treatment.
We have also demonstrated that there are numerous swallowing assessment tools, but that most of these await disease-specific validation. There is a disconcerning lack of interventional therapies due to this, but also as a result of a lack of clinically meaningful outcome measures.