Neuromuscular diseases (NMDs) affect the development and growth of the neuromuscular system in children. The pathology can occur anywhere along the neuromuscular pathway, from the brain to the nerves to the muscle fibers. These diseases have a profound impact on the quality of life not only of children but also of their families. The predominant manifestation in NMDs is hypotonia, which leads to muscle weakness and fatigue, reduced mobility, and decreased physical performance. However, multiple organ systems can be affected, with resulting orthopedic, cardiac, infectious, respiratory, and nutritional problems. Children with NMD present an increased risk for several dietary and feeding difficulties because of their neuromuscular diagnosis, presentation, and severity. These problems include chronic gastrointestinal issues (constipation, dysphagia, gastroesophageal reflux, and diarrhea), dysphagia, malnutrition, and body composition alterations. As a result, compared to the overall pediatric population, infants and children with NMD are more likely to be malnourished, ranging from failure to thrive to overweight or obesity. Disease-specific guidelines vary in level of detail and recommendations for dietary management. Overall, nutritional data available are sparse, with the exception of Duchenne muscular dystrophy, spinal muscular atrophy, and congenital muscular dystrophy. The purpose of this review is to describe the spectrum of nutritional challenges in children with NMD and to summarize the main dietary and gastrointestinal recommendations for each neuromuscular disorder to provide guidance for daily clinical practice.

Pediatric neuromuscular disorders (NMDs) include a variety of diseases where the peripheral nervous system is the main site of abnormalities or damage. These include disorders of the anterior horn cell (i.e., spinal muscular atrophy, poliomyelitis, and amyotrophic lateral sclerosis), peripheral nerve (i.e., Charcot-Marie-Tooth disease), neuromuscular junction (i.e., congenital myasthenic syndrome), and musculature (i.e., myopathies and muscular dystrophies)[1]. The main and most frequent symptom in NMDs is hypotonia, which leads to muscle weakness, fatigue, reduced mobility, and decreased physical performance. Furthermore, a deterioration of the quality of life for NMD patients and their families is frequently brought on by orthopedic, cardiac, infectious, and respiratory issues[2]. Nutritional and gastrointestinal complications are also frequent in NMDs, but they are sometimes underestimated[2]. Compared with the general pediatric population, infants and children with NMDs are at higher risk of malnutrition, ranging from failure to thrive to being overweight or obese (Table 1)[3,4].

Moreover, they present an increased risk of developing chronic gastrointestinal (GI) conditions such as constipation, gastroesophageal reflux disease (GERD), dysphagia, and delayed gastric emptying. Several aspects related to nutrition need to be considered when prolonging survival in patients with NMD, including the negative impact of overnutrition on glucose metabolism, mobility, respiratory, and cardiac function and the effects of undernutrition on muscle development and strength ventilation function. In addition, difficulty chewing and swallowing can lead to a higher risk of aspiration, which predisposes to infectious diseases and respiratory issues[2]. Micronutrient deficiencies, such as vitamin D and calcium deficiencies, can affect bone health, particularly in children with Duchenne muscular dystrophy (DMD) who receive steroids (side effects include bone loss and fractures)[4,5].

The importance of optimal nutritional and GI management lies in reducing complications and mortality and improving the quality of life in this group of patients[4,5]. A particular attention to these issues is required with an early and appropriate approach. The purpose of this review is to describe the spectrum of nutritional problems in children with NMD and to provide specific dietary and GI recommendations for each NMD.

For this review, relevant studies published over the last 20 years were identified via a PubMed/Medline (http://www.ncbi.nlm.nih.gov/pubmed/) search using the following keywords or combinations of keywords: neuromuscular disorders, malnutrition, overnutrition, diet, GI symptoms, management, guidelines. All of the most common neuromuscular disorders were afterwards used as search terms to review literature data regarding the GI and nutritional issues. Particular emphasis was placed on evidence-based guidelines and all high-quality studies illustrating current management pathways. Additional papers were identified by reviewing reference lists of relevant publications. Non-English publications were excluded. A systematic approach to study selection was not implemented. Instead, data were extracted based on their relevance to the topic.

Spinal muscular atrophy (SMA) is an autosomal recessive neurodegenerative disease caused by a homozygous mutation or deletion in the survival motor neuron 1 (SMN1) gene. Defects in the SMN1 gene cause the selective destruction of alpha motor neurons in the anterior horn cells of the spinal cord and brainstem. Clinical manifestations include muscle atrophy and weakness, resulting in swallowing and feeding difficulties and respiratory complications. SMA affects approximately one in 6000-10000 newborns worldwide[18]. The classification of SMA consists of four subtypes based on age of onset and maximal functional ability: very weak infants unable to sit unsupported, onset < 6 mo of age (type 1), nonambulant patients able to sit independently, onset between 6 and 18 mo of age (type 2), ambulant patients with onset between 18 mo and 18 years (type 3), and adult onset SMA (type 4).

The SMA multidisciplinary care focuses on reducing complications and improving quality of life. Symptoms of GI dysfunction, including constipation, delayed gastric emptying, and GERD, are important determinants of mortality and morbidity, for example dysphagia and reflux can lead to pulmonary disease[19].

In 2007, a consensus statement was published by the International Conference on the Standard of Care for SMA. A two-part update of the topics covered in the prior recommendations was published in 2018 as a result of the more current data publications and more generally made advancements in the themes mentioned in the original version[20].

One of the nine topics included in this update focused on nutrition. The main nutritional goals, which are slightly different for each type of SMA, include weight control, swallowing and dysphagia management, and management of GI dysfunction. Regular growth checks are important for all SMA types. Growth and body composition are measured using a variety of methods, such as basic anthropometry, dual-energy X-ray absorptiometry, and bioelectrical impedance analysis[19,20].

Specific growth charts for SMA are not currently available. Due to modifying body composition in standardized SMA growth charts, it may be helpful to monitor growth trends rather than monitor weight. In contrast, children with SMA type III are prone to overeating and obesity from physical inactivity and have reduced energy needs due to lower basal metabolic rates[3].

For optimal care, a nutritionist assessment is recommended every 3-6 mo for younger children and annually for older children and adults[20]. In addition, a qualified dietician should also promote healthy nutrition and keep track of hydration, macronutrient, and micronutrient intake, particularly calcium and vitamin D intake for bone health. Calcium and vitamin D supplements are recommended if the levels are low. It’s crucial to inquire and record the specifics of GI symptoms in all subjects, which could include GERD, constipation, use of bowel regulators, delayed gastric emptying, and vomiting.

Infants and children with SMA types I and II should receive gastrostomies in the first few months of life to avoid the risk of malnutrition. This approach is also recommended to reduce the risk of respiratory infections[20]. Nutritional and GI evidence for SMA children is summarized in Table 3.

Charcot-Marie-Tooth disease (CMT) is the most common inherited NMD with an estimated prevalence of up to 40 in 100000 people, which corresponds to 200000 cases in the European Union[24]. The disease generally appears in the first two decades of life and progresses slowly over many years. It is a genetically heterogeneous disorder resulting from mutations in genes that encode proteins in various locations, which include compact and non-compact myelin, Schwann cells, and axons. These proteins are involved in a wide variety of functions, including myelin compaction and maintenance, formation of the cytoskeleton and axonal transport rich, as well as mitochondrial metabolism[25]. Since motor and sensory peripheral nerves are affected, CMT is also known as hereditary motor and sensory neuropathy. Distal weakness, hand and foot deformities, slow loss of sensory perception, and mild to moderate disability are the most common clinical phenotypes.

There is still no effective drug therapy for CMT. A multidisciplinary approach is necessary for therapeutic management; the neurologist should work closely with other professionals such as orthopedics for the surgical treatment of skeletal deformities and soft tissue anomalies[1,25].

There are no specific nutritional recommendations for this patient group, and the nutritional approach must be evaluated individually. Sometimes the use of oral nutritional supplements may be recommended. Skeletal deformities may be associated with an increased risk of GERD.

Congenital muscular dystrophies (CMD) are a group of genetic neuromuscular disorders defined by muscle weakness that appears at birth or in the first few months of life and the presence of dystrophic biopsies and/or increased creatine kinase, two markers that are diagnostic of a muscular dystrophy[26]. The identification of different CMD subtypes backed by precise gene identification has been made possible by developments in molecular genetics and histopathology techniques[27]. Despite rapid advances in basic research, clinical care for patients with CMD remains poor due to the rarity of this pathology and the difficulty of differentiating clinical phenotypes.

The International Standard of Care Committee for Congenital Muscular Dystrophy published a consensus statement in November 2009 on standards of medical care divided into 7 areas: Diagnosis, neurology, pulmonology, orthopedics, gastroenterology and nutrition, speech, and oral care, cardiology, and palliative care[28]. Main topics are nutrition and growth, food intake, GI motility, and oral care[28]. There are no specific growth charts or data on the energy and nutritional needs of CMD children, and this makes monitoring nutrition and growth even more difficult[28]. Patients with CMD often have a growth trajectory that is below age, and one of the most typical childhood problems is malnutrition and poor weight gain. Instead, obesity should be considered in adults due to the limited mobility of these patients.

In this group of patients, special attention needs to be paid to feeding and swallowing problems, which should be evaluated regularly during routine clinic visits, asking about: (1) Length of meals; (2) frequency of meals; (3) frequency of lung infections; (4) difficulty chewing (choking and coughing); (5) change in the structure of food; (6) stress in the family or enjoyment of meals for the child and parents; and (7) ability to eat independently. Videofluoroscopy can reveal difficulties in the oral phase, a delay in pharyngeal swallowing, and increased risks with aspiration[28]. In the case of dysphagia and feeding problems, treatment strategies may include adjustments in standing positioning and sitting, support for self-feeding, which include adjustment of feeding utensils and devices, safe swallowing procedures, and texture modification. When symptomatic treatment is inadequate, the use of tube feeding must be considered.

GERD and GI dysmotility, i.e., delayed gastric emptying and constipation, are common in CMD patients. In order to minimize the risk of gastroesophageal reflux and dysmotility, the frequency and volume of tube feeding should be adjusted and attention should be paid to adequate fluid intake, posture, and movement. Medical treatment includes use of proton pump inhibitors and treatment with antacids and laxatives for GERD and constipation, respectively[28]. Increasing fiber intake or using natural food enteral formulas could also be considered to treat constipation[16,17].

Myotonic dystrophy (MD) is the most common form of muscular dystrophy in adults, with an estimated prevalence of 1 in 8000[29]. Myotonia and muscular dystrophy were traditionally used to name this multisystem condition. Myotonic dystrophy type 1 (MD1, Steinert disease) is caused by a cytosine, thymine, and guanine repeat expansion in the 3^rd untranslated region of the myotonic dystrophy protein kinase gene on chromosome 19[30]. MD1 patients range from asymptomatic or moderately severe, late adult onset to severe congenital variants, with an autosomal dominant inheritance pattern. In particular, congenital MD is the most severe form and may present prenatally with polyhydramnios and reduced fetal movements.

Respiratory failure, hypotension, feeding difficulty, weakness, and tented or fish-shaped upper lips are all frequent at birth[30]. Facial weakness, dysarthria, myotonia, low intellect, and cardiac conduction anomalies characterize the childhood-onset (1-10 years) phenotype[31]. Patients may gradually present with early cataracts, myotonia, muscle weakness or atrophy, fatigue, excessive daytime sleepiness, central or obstructive apnea, respiratory failure, cardiac arrhythmia, insulin resistance, dysphagia, GI dysmotility, cognitive impairment, cluster C personality traits, and/or mood swings.

No particular dietary risks are reported for MD patients, although each patient must be assessed on an individual basis. The major GI problems that arise during the course of the disease are dysphagia, postprandial bloating or abdominal pain, diarrhea, constipation, and/or fecal incontinence, and cholelithiasis[31]. Drug therapy for the treatment of GERD does not differ from that for other patient groups[32].

The management of children with NMDs, who frequently present with nutritional issues like inappropriate weight and body composition, difficulty swallowing and feeding, constipation, and GERD, places a high priority on nutritional care. Effective interdisciplinary management can considerably lower morbidity and mortality even though there is often no treatment available.

This present study is an unstructured, narrative review, so there are inherent limitations, such as the lack of direct comparison between studies. However, we described the methods for selecting and reviewing literature to make it possible to verify or replicate these results. Moreover, the heterogeneity of the published studies on the nutritional and GI care of pediatric patients with NMDs made it challenging to implement a systematic approach to study selection and interpretation. The aims of the present article were to report the spectrum of nutritional problems in children with NMD and to provide clinicians with specific dietary and GI directions for each NMD while highlighting the knowledge gaps in this topic. There are no specific nutritional and GI recommendations for all of the NMDs in the scientific literature currently available, especially in the pediatric age group. More nutritional and GI data are available for DMD and SMA. Future studies should focus on creating disease-specific treatment guidelines, including dietary recommendations based on age group, physical activity status, and swallowing problems. This patient population is at high nutritional risk, so a proactive attitude is recommended. The clinician should plan for the early use of tube feeding and the appropriate selection of the most appropriate formula, with a particular interest in enteral hydrolyzed formulas. In terms of GI symptoms, the greatest challenges lie in the treatment of GERD and chronic constipation. The use of drugs to inhibit acid secretion should be prompt. The possibility of increasing fiber intake or the use of natural food formulas in enteral feeding should also be considered to further assist in the management of constipation.