Introduction

Sucking, chewing, and swallowing are vital functions that are dependent upon the coordinated interaction of a set of neural structures designated by several authors as the “oromotor system” (OMS). Also dependent on this system are other not-so-vital but important functions such as language motor articulation and gestural communication by means of facial expression. Direct control of the OMS is located in the brainstem. Sensory inputs and motor actions are mediated through neuronal groups, the cranial nerve nuclei, located along the brainstem axis. These nuclei are, in turn, under the control of cortical and subcortical structures . This neuronal network allows the integration of the sensory information received and the voluntary or involuntary motor responses to these stimulations. The interaction of all these circuits allows the generation of complex reflexes and of voluntary actions that contribute to functions, such as sucking, chewing, swallowing, phonation, and facial nonverbal communication. The OMS can be disrupted in many ways and at different levels, giving rise to a multitude of disorders, most of them congenital, with clinical manifestations presenting and persisting throughout childhood.

Many aspects of OMS dysfunction have been reviewed in the literature under different headings. The most common terms used in monographs or pediatric textbooks have been: congenital flaccid bulbar paresis, congenital suprabulbar and pseudobulbar paresis, feeding or swallowing disorders in children, and dysphagia in childhood. Surprisingly, despite the fact that in most instances these disorders are caused by nervous system diseases, no monographs or reviews have approached their study from a neurological perspective and much less from a neuromuscular disorder (NMD) viewpoint. Indeed, pediatricians and child neurologists are often faced with neonates or infants with facial diplegia, feeding difficulties, dysphagia, muscle hypotonia, respiratory distress, and joint contractures that sometimes are associated with other craniofacial malformations. The causes for this constellation of clinical signs and symptoms are manifold. Congenital tumors, vascular malformations, severe perinatal trauma or hypoxic-ischemic events and restricted prenatal disruptive lesions, or malformations of the cerebral hemispheres or the brainstem, as well as congenital NMDs, are known to produce the aforementioned clinical picture during the neonatal period or infancy. Over the last 25 years, we have developed a concept and classification for disorders of the OMS ( Table 47.1 ) that takes into consideration both the cause and the anatomical location of the underlying disease. As can be deduced from Table 47.1 , occasionally both feeding and/or speech problems are reversible because the defect causing these functional difficulties can be corrected or because the clinical manifestations subside after a more or less prolonged period of time, as is the case for patients with acute illnesses, central nervous system (CNS) maturation delay, or mild congenital neuromuscular disorders. In this chapter, we will consider only those disorders giving rise to persistent or irreversible clinical manifestations.

Oromotor dysfunction (OMD) is among the possible consequences of perinatal hypoxic-ischemic injuries. These encephalopathies initially give rise to a suprabulbar syndrome with generalized hypotonia, lethargy, and facial diplegia with salivary incompetence that, subsequently, will result in feeding difficulties, respiratory complications, and clear signs of CNS involvement such as poor axial tone, spastic hypertonia or dystonia of the limbs, and dysarthria. OMD arising from restricted bilateral hemispheric involvement produces a suprabulbar paresis syndrome, first reported by Worster-Drought and characterized by orofacial paresis, dysarthria, difficulties of voluntary tongue motor control, mild pyramidal signs, and, characteristically, a dissociation of cortical and subcortical motor control. Genetic factors, prenatal infections, and vascular lesions are considered the most likely causes of this disorder. Newborns with congenital dysfunction of multiple cranial nerves are also a challenging diagnostic problem. Throughout the years, we have been able to identify a group of patients with a recognizable symptom complex characterized by a variable combination of congenital cranial nerve dysfunction, decreased muscle tone, and, in many cases, mild signs of pyramidal tract involvement due to prenatal disruptive brainstem lesions or to malformations of the brainstem, for whom we have proposed the term “brainstem dysgenesis” (BSD). Recently, other authors have postulated that the orofacial malformations seen in Pierre Robin, Moebius, and CHARGE syndromes are also the product of embryonic defects in brainstem development. In our experience, a clear-cut division can be drawn between the natural history of OMD arising from CNS diseases and that of OMD arising from NMDs. In the first case, when initial feeding and swallowing problems subside, learning difficulties, speech articulatory problems, and seizures (frequently) become apparent. In the natural course of most NMDs, as the initial muscle hypotonia, respiratory problems, and feeding difficulties improve, food sticking due to inadequate chewing, poor control of saliva, pulmonary aspiration of food or fluids, poor oral hygiene and dental decay, speech intelligibility, lack of facial expression, joint contractures, and skeletal deformities become the major clinical problems.

Regardless of the disease causing the OMD, it is important to recognize that its impact on the three domains—body structures and functions, activity, and participation—established in the International Classification of Functioning, Disability, and Health changes as children grow and are exposed to different environmental situations. In newborns and infants with NMDs, the greatest impact on health and well-being are respiratory complications and undernutrition due to poor sucking and swallowing. As a result, interventions must focus on preventing food aspiration and ensuring appropriate nourishment by providing alternative methods of ingestion. At the other end of childhood, the school setting may have its greatest impact on well-being and participation because teachers and peers may not be aware that the physical impairment and/or communication problems of children with OMD may prevent them from participating in most activities. Interventions may seek to alter the environment by training the peers and teachers to recognize and understand the child’s communication, and adapt the physical surroundings and pattern of interaction, so the child can participate in all regular classroom activities. Because change in health issues occurs as children with OMD get older, it is crucial that a team of health professionals be involved in the care of these youngsters and their families. In practice, individual members of the health team become central at certain points in the patient’s disease and then move into the background as other problems are encountered and addressed. Because health professionals revolve through the children’s lives, parents may remain the only constant members of the team with recollection of the outcomes of all the interventions or treatments. As clinicians, we should bear in mind that each new health issue faced by a child demands readjustment. Information should be shared with parents to enable them to give their opinion and to make the decisions that will affect their child’s immediate and long-term health and well-being.

Oromotor Dysfunction Due to Neuromuscular Disorders

The central symptom of NMDs is muscle weakness, which often has a progressive course. The degree and location of muscle group weakness can be unevenly distributed, depending on the underlying NMD, and, in a number of NMDs, both skeletal and smooth muscles are involved. Weakness in some NMDs and in most congenital NMDs involves facial, oral, and pharyngeal musculature and is responsible for the multiple OMS functional problems ( Box 47.1 ). Other factors such as respiratory insufficiency, gastroesophageal reflux, esophageal dyskinesia, laryngomalacia or/and tracheomalacia, failure to thrive, and congenital heart disease are often associated with NMDs and, in addition to OMD, can have an impact on feeding, swallowing, and speech production, and must also be taken into consideration.

Facial muscle weakness impairs eye closure, lip function, and facial expression. Characteristically, the lower lip is flaccid and rotated outwards, and the upper lip is retracted. An expressionless face affects the ability to express emotions as well as the use of facial expressions for nonverbal communication and social interaction. Weak masseter muscles often lead to an open mouth posture; the tongue has a low and forward position in the oral cavity and its range of movement and fine motor skills are often impaired. Chewing ability can be affected by weak masseter muscles, jaw contractures, and also by malocclusion. Altered pressures on the teeth and dental arches in children with weak and hypotonic perioral muscles have an impact on facial growth and increase the risk for developing malocclusion. Decreased jaw mobility and restricted oral opening is sometimes present from birth, but in some NMDs, the progression of the disease will eventually lead to contractures in the temporomandibular joints. Buccinator muscle weakness contributes to food pooling into the cheeks during bolus preparation. These muscles, together with the tongue, help position the food bolus between the molars for efficient chewing. Weak oral and pharyngeal muscles interfere with all phases of swallowing. During the preparatory oral phase, lip closure is necessary to prevent food leakage and promote efficient swallowing. The lips are also active when taking food from the fork or emptying the spoon and when drinking from a cup, glass, or straw. Weakness of the muscles that elevate and retract the soft palate to accomplish velopharyngeal closure allows food to enter the nasal cavity and indirectly impairs swallowing efficiency. During the oral phase of swallowing, the tongue, the perioral, and the velopharyngeal muscles must be strong and coordinated to achieve effective swallowing and emptying of the mouth. The pharyngeal and esophageal phases are also dependent on strong, coordinated muscles for safe and effective swallowing. Weakness of the muscles of the floor of the mouth, including the mylohyoid, geniohyoid, and anterior belly of the digastric muscle, limits the upward and forward movement of the hyoid bone and larynx, thereby restricting the adequacy of the opening of the upper esophageal sphincter.

A fine temporal coordination between respiration, chewing, swallow initiation, and airway closure is required to prevent aspiration. During swallowing, the larynx is closed to prevent aspiration as the bolus passes the airway. Between swallows, during chewing, and during bolus collection in the pharynx, the airway remains open and breathing continues. Newborns are one exception; in them, the oral phase is inseparable from the sucking reflex. On contact with the nipple, rhythmic contractions of the tongue occur and the lips are pressed together. The frequency of sucking varies from 0.6 to 2 per second. The pharyngeal phase occurs in a reflex manner after each suck so that the organization 1 suck/1 swallow and its coordination with respiration occur in an entirely automatic sequence. Deglutition apnea occurs simultaneously with the elevation of the soft palate, even before the closing of the glottis. Swallowing occurs during the natural pause between the end of inspiration and the onset of expiration. This apnea lasts 450 to 600 milliseconds. Thus, the newborn can feed itself without interrupting respiration, the rate of which is governed by the sucking rhythm and returns to its previous baseline rate when the meal is finished.

Optimal phonation and speech production also require respiratory strength, breath support, and control to manage the airflow stream. Respiratory health and function will therefore relate to swallowing and speech performance. This interrelationship can be affected by weak and poorly coordinated muscle movements. Weak and hypotonic oral and velopharyngeal muscles and respiratory insufficiency are responsible for the dysarthria observed in individuals with NMDs. Common symptoms are a low voice, blurred speech, hypernasality, compensatory articulation of bilabial consonants due to impaired lip function, and weak pronunciation of consonants.

Saliva is produced within the mouth and is swallowed automatically every few minutes throughout the day. Drooling can vary from minute to minute depending on factors such as hunger, thirst, fatigue, anxiety, excitement, and the circadian rhythm of saliva production over time. Drooling is not caused by hypersalivation but rather by OMD. Patients with NMDs and OMD are at risk of drooling and lung aspiration of oral secretions because its control is dependent upon effective lip closure and swallowing, as well as upon an effective sensory system able to react to the discrete inputs produced by the oral secretion volume.

Neuromuscular Disorders with Associated Oromotor Dysfunction

Few studies have examined the relationships between OMD and NMDs. The lack of medical research on this subject probably reflects the fact that in the last 40 years, scientific interest has been centered on elucidating the definitive cause and pathological mechanisms of NMDs rather than on establishing the intimate relationship between specific groups of peripheral nervous system diseases and their regularly associated clinical dysfunctions in order to improve NMD management. OMD can be present in some acquired NMDs or be identified at some point of the natural course of many inherited, progressive NMDs. OMD is a serious clinical problem in the advanced phases of this last group of illnesses, when weakness hampers respiratory function and involves muscles of the OMS; also, the lack of coordination due to altered sensory input of inappropriate motor responses interferes with the correct functioning of the OMS. Yet, in the early phases of NMDs, OMD is also a particularly common and important clinical problem that interferes with fetal development and shows clinical symptoms at birth or during the first few months of life. The degree and number of clinical manifestations closely relate to the phenotypic severity of the underlying NMD. In NMDs with onset during fetal development, it is difficult to distinguish genuine OMD from other associated factors such as multiple joint contractures (including temporomandibular ankylosis), micrognathia, retrognathia, macroglossia or microglossia, and weakness of respiratory muscles that, unquestionably, have a major impact on proper oromotor function.

The most common NMDs associated with OMD are depicted in Box 47.2 . Two main groups of NMDs according to the age at onset of clinical manifestations have been considered. Although we are aware that a large number of NMDs, at some point in their natural course, give rise to OMD and therefore constitute a major management problem in the field of NMDs, in our experience the neonatal form of congenital myotonic dystrophy, spinal muscular atrophy (SMA) Type IA or type I, congenital myopathies, congenital muscular dystrophies, and congenital myasthenic syndromes are, in order of frequency, the most commonly found NMDs associated with OMD throughout childhood. All the aforementioned disorders have been extensively described in other chapters of this book, and therefore only a brief note pointing out the relationships between each group of NMDs and their most commonly associated OMD will be presented here. As suggested in the introduction of this chapter, all types of congenital NMDs should be differentiated from arthrogryposis, BSD, Worster-Drought or Prader Willi syndromes (see Chapter 6 , Chapter 7 ). All of the aforementioned conditions can present during the neonatal period with profound generalized hypotonia, respiratory problems, multiple cranial nerve involvement, and feeding difficulties requiring enteral tube nutrition.

Slowly progressive muscle weakness and myotonia are cardinal symptoms of myotonic dystrophy type I. Severe hypotonia, respiratory insufficiency, and sucking difficulties are present in newborns who have the congenital form of myotonic dystrophy and particularly in those born prematurely. In this form of myotonic dystrophy, muscle tone and muscle strength improve during the first 2 years of life but, later on in the course of the disease, myotonia in the hands, jaws, and tongue appears and muscle weakness slowly returns. A moderate OMD is present in nearly all children with infantile myotonic dystrophy due to delayed oromotor development and weak hypotonic muscles. The face and jaw muscles are generally the most affected, causing impaired facial expression, an open mouth, and difficulties with chewing. Craniofacial development of many individuals with myotonic dystrophy type I is characteristic, with a more vertical cranial growth, narrower maxillary arches, and deeper palatal depth than healthy controls. Malocclusion is common, especially an anterior open bite and a cross bite. Impaired lip articulation and hypernasality due to velopalatine insufficiency contribute to dysarthria, although associated intellectual disabilities also influence speech and language development. Other commonly affected organs or systems in myotonic dystrophy type I are heart, smooth muscle, gastrointestinal tract, endocrine system, and CNS; their clinical involvement can aggravate the OMD problems.

Infants with SMA type I (see Chapter 8 ) often have a weak cry and cough, paradoxical respirations due to the relative sparing of the diaphragm, and difficulties with breathing, feeding, and swallowing as well as tongue fasciculations, but this last sign is not known to cause any OMD. Speech is rarely affected in SMA types II–IV, but patients are at risk of developing a decrease in jaw-opening ability as the disease progresses. Increasing difficulties with chewing and swallowing in children with SMA type II have also been reported. Unusual phenotypes of congenital motor neuron disorders include SMA with arthrogryposis (XL-SMA; SMAX2), congenital SMA (5q) with arthrogryposis (SMA type IA), distal infantile spinal muscular atrophy with diaphragmatic paralysis (SMARD1), early-onset myopathy with areflexia, respiratory distress, and dysphagia (EMARDD), congenital lethal contractures syndromes, and SMA with pontocerebellar hypoplasia type I; in these conditions, the onset of the disease occurs prenatally and the infants are born with multiple joint contractures (arthrogryposis) as well as with respiratory problems that contribute to their OMD and eventually lead to the patient’s death. In congenital lethal contractures syndrome and acute forms of SMA type I, brainstem motor neurons are involved; in the latter condition, dysphagia may be present from birth but facial muscles are spared. Extraocular muscles are characteristically involved in congenital SMA with arthrogryposis. Again, all these rare forms of congenital motor neuron disorders are very difficult to differentiate clinically from BSD and arthrogryposis. Progressive bulbar paralysis of childhood or Fazio-Londe disease is a rare inherited disorder. The age of onset ranges from 12 months to 12 years. The most frequent presenting symptoms are stridor, followed by ptosis, dysarthria, facial palsy, and dysphagia. Progressive involvement of cranial nerves and respiratory difficulties are responsible for the patient’s death within a few years. Brown-Vialetto-van Laere syndrome 2 (BVVLS2), or progressive bulbar palsy with sensorineural deafness, is considered to be an allelic form of Fazio-Londe disease and is due to a riboflavin transporter defect. Deafness, gait disturbance, and exercise intolerance as well as the possibility of medical treatment are its distinctive traits.

Congenital myopathies are defined by the early onset weakness together with characteristic pathological findings on muscle biopsy and normal to slightly elevated creatine kinase levels (see Chapter 28 ). Because of advances in molecular genetics, congenital myopathies are now understood to be a more diverse group of disorders than initially suspected. As a group, they show varied and overlapping clinical and histologic phenotypes, but they share more genotypes than anticipated. In fact, many of the histological features on muscle biopsies, which were used in the past to distinguish them, occur on a spectrum that crosses the boundaries of individual genetic entities. Children with congenital myopathies have muscle weakness and delayed motor development. Severe phenotypes often have significant respiratory problems that lead to the patient’s demise or that require prolonged ventilatory support. Feeding impairment, dysphagia, drooling, and dysarthria with hypernasal speech are frequent findings due to the profound weakness of the pharyngeal and facial muscles. Involvement of the extraocular, facial, and oromotor musculature is not infrequent in this group of myopathies. See Case Example 47.1 .

Congenital muscular dystrophies (CMD) are a group of genetic disorders in which weakness and abnormal muscle histologic features are present at birth (see Chapter 29 ). The mode of inheritance for most of them is autosomal recessive with significant genetic heterogeneity. Muscle weakness is slowly progressive or not progressive, depending on the individual disease, but complications of the dystrophy can become more prominent over time. From a practical clinical point of view, CMD can be divided into two subgroups, one with normal mental development and the other with associated intellectual disability. Magnetic resonance imaging of the brain, therefore, is imperative in the clinical approach to CMD as it reveals abnormalities of brain formation and neuronal migration or changes in the white matter. Most forms of CMD with abnormalities of brain formation that have been defined on a molecular level show alterations of dystroglycan O-linked glycosylation. The main phenotypes in this group have been delineated on clinical grounds and include Fukuyama CMD, muscle-eye-brain disease, and Walker-Warburg syndrome, but variations and overlapping phenotypes are frequent. Common clinical characteristics of this group of NMDs include severe muscular dystrophy, neuronal migration defects including lissencephaly type II (cobblestone lissencephaly), pachygyria, cerebellar and brainstem abnormalities, and variable ocular anomalies. OMD is present in most cases, congenital contractures are common, and some infants require ventilatory assistance and tube feeding. Primary laminin-2 (merosin) deficiency causes one of the most common single forms of CMD. These patients usually present at birth or during the first month of life with muscular hypotonia, joint contractures, respiratory insufficiency, and feeding problems. Facial weakness is often prominent and motor development is markedly delayed, precluding independent ambulation. Most patients develop respiratory insufficiency requiring ventilatory support during the first decade of life. Gastroesophageal reflux, feeding difficulties, and poor nutrition are common. Even though abnormalities of the white matter are commonly found in laminin-2 mutations, they generally do not prevent normal mental development. Collagen VI is a component of the extracellular matrix that does not belong to the group of dystrophin-associated proteins. Autosomal dominant mutations of collagen VI are known to cause Bethlem myopathy. Autosomal recessive mutations give rise to a more severe clinical phenotype known as Ullrich myopathy. Common clinical manifestations of patients with collagen VI deficiency are generalized muscle weakness, striking hypermobility of distal joints, and variable contractures of more proximal joints. Additional clinical findings include kyphoscoliosis, protruding calcanei, and follicular hyperkeratosis. Patients with the Ullrich phenotype may develop severe respiratory insufficiency but seldom have OMD. CMD with rigid spine is characterized by early rigidity of the spine and a restrictive respiratory syndrome. These signs are often preceded by hypotonia and predominant axial muscle weakness in the first months of life. Mutations in at least three genes ( SEPN , FHL1 , and LMNA ) have been linked to the rigid spine phenotype. SEPN1 gene mutations are associated with multiminicores, which are typically smaller in size than those associated with recessive RYR1 mutations. Clinically, patients with SEPN1-related disease manifest with a predominantly axial myopathy with weak neck flexors, spinal rigidity, and scoliosis as well as prominent respiratory compromise disproportionate to the extremity weakness. The respiratory compromise may be progressive even when limb weakness remains relatively mild and static. Bulbar weakness has been reported in some cases while extraocular muscle involvement does not seem to occur. The majority of SEPN1 patients are able to achieve and maintain independent ambulation. FHL1 gene mutations give rise to a slowly progressive clinical picture that, due to the severe hyperextension of the neck, interferes with or impedes oral feeding in the late stages of disease.

Facioscapulohumeral muscular dystrophy occurs in all age groups, but onset is most common during adolescence. About one third of patients have mild symptoms. The inheritance pattern is autosomal dominant, and the most common cause of the disease is a contraction of a repeat (D4Z4) on chromosome 4 (4q35) (see Chapter 32 ). A severe infantile form is often associated with hearing loss (Coats’ syndrome). Asymmetric weakness is characteristic and is primarily located in the face, shoulder girdle, and upper arm muscles. The most commonly affected facial muscles are the sphincter muscles that close the eyes (orbicularis oculi) and the mouth (orbicularis oris). In addition to impaired facial expression and eye closure, facial weakness can affect saliva control and cause milder problems related to eating and drinking. The progression of muscle weakness and wasting is relatively slow. Speech is rarely affected during childhood.

Disorders of neuromuscular transmission (see Chapter 25 , Chapter 26 , Chapter 27 ) have variable pathophysiology and expression. Symptoms usually appear during the first few months or years of life, and typical clinical findings include feeding difficulty, respiratory dysfunction, ophthalmoparesis, ptosis, and hypotonia. Symptoms may worsen with crying and physical activity. In neonatal transient myasthenia gravis there is no correlation between the severity of the maternal disease and that of the infant. Symptoms appear within the first few hours and the mean disease duration is 18 days. A prenatal onset results in a severe form with polyhydramnios, arthrogryposis, and severe hypotonia. Occasionally, maternal disease may be latent and acute choking episodes may be a presenting symptom in a floppy baby with associated bulbar weakness. Congenital myasthenic syndromes (CMS) comprise a group of heterogeneous genetic diseases whose clinical manifestations vary depending on the syndrome subtype. Some patients present with signs at birth or shortly after, whereas others, especially those with mild presentations, go undiagnosed until adolescence or adulthood. CMS can be classified as presynaptic, synaptic, or postsynaptic, depending on the location of the primary defect within the neuromuscular junction. Postsynaptic defects comprise up to 75% to 80% of all cases. Abnormalities of presynaptic neuromuscular transmission constitute the rarest forms of CMS. The subtype of CMS with episodic apnea is attributed to deficiency of choline acetyl transferase, and its main clinical manifestations include sudden episodes of respiratory distress and bulbar weakness causing apnea. These episodes may be triggered by fever, infections, or stress. Endplate acetylcholinesterase deficiency begins in childhood and is characterized by weakness, muscle atrophy, and slow pupillary response to light stimulation after the administration of acetylcholinesterase inhibitors. Skeletal deformities (lordosis or scoliosis), ptosis, ophthalmoplegia, dysphagia, difficulty breathing, and limb weakness can occur with disease progression. Defects of the acetylcholine receptor genes can cause CMS that can begin in childhood, adolescence, or adulthood. In affected families, the pattern of inheritance is autosomal recessive. The main signs include hypotonia, delayed motor development, ptosis, ophthalmoplegia, weakness that may worsen on exertion, skeletal deformities (arthrogryposis, lordosis, or scoliosis), muscular atrophy, dysphagia, and respiratory difficulty. The fast-channel syndrome, due to the abnormal activity of the acetylcholine receptor ion channel, presents in neonates and infants, and its main clinical signs include ptosis, ophthalmoplegia, dysphagia, and weakness. The three main groups of postsynaptic subtypes of CMS with defects of the acetylcholine receptor complex are rapsyn deficiency, which is typically of neonatal onset and often associated with arthrogryposis and bulbar symptoms; Dok-7 myasthenia; and MuSK deficiency. Their clinical symptoms are similar to those of agrin defects and involve ptosis, ophthalmoplegia, and proximal weakness of the limbs. Other rare forms of postsynaptic CMS and OMD include Escobar syndrome, which represents the association of CMS with arthrogryposis multiplex congenita, pterygium, and difficulty breathing, and CMS with centronuclear myopathy.