Down Syndrome for the Otolaryngologist -A Review

Causes and Epidemiologic Context

Down syndrome was first described in 1866 by John L. Down6 as a phenotype of common anatomic abnormalities and intellectual disability. Trisomy 21 occurs when chromosome 21 fails to separate during egg or sperm development, which results in an extra copy of chromosome 21. Partial or complete trisomy 21 is the most frequent genomic cause of Down syndrome, and a free trisomy 21 is present in approximately 95% of affected individuals, while translocation exists in 5% and mosaicism occurs in 2%.

Down syndrome has been associated with numerous anatomic characteristics, specifically retrognathic mandible, midface hypoplasia, relative macroglossia, hypertrophy of Waldeyer ring, subglottic stenosis, external auditory canal stenosis, inner ear dysplasia, laryngeal cleft, and eustachian tube malformation. Systemic characteristics that may affect otolaryngology-based conditions include hypotonia, short stature, cervical spine abnormalities, congenital heart disease, immune deficiency, and predisposition to obesity.

As the global population expanded during the past century, the lifetime prevalence of Down syndrome increased substantially. With a growing and aging population of individuals with Down syndrome, the likelihood of a patient with this condition entering an otolaryngology clinic is quite high.

Hearing and Communication Considerations

A morphologically defining characteristic of Down syndrome is the position of the pinna and narrow external auditory canal (EAC), which may result in common otologic concerns requiring evaluation by an otolaryngologist. Stenosis of the EAC is present in approximately 40% to 50% of individuals with Down syndrome and is associated with difficulty surveilling the middle ear, recurrent cerumen impactions, and development of conductive hearing loss (CHL). When the tympanic membrane is not easily visualized, regular evaluation and cerumen cleaning, particularly in children younger than 3 years old, every 3 to 6 months may ensure adequate surveillance of the middle ear space to prevent development of chronic otitis media (OM).

Conductive hearing loss is present in up to 80% of children with Down syndrome with OME, making treatment of middle ear effusion paramount to preventing adverse effects on language development

Hearing loss for individuals with Down syndrome is not limited to CHL. There is also a high percentage of sensorineural hearing loss (SNHL) and mixed hearing loss (MHL) among this patient population. The American Academy of Pediatrics (AAP) recommends that all newborns undergo a hearing screening by 1 month of age using auditory brain stem response or otoacoustic emissions testing. Then, hearing assessments for children with Down syndrome are recommended every 6 months until the age of 3 or 4 years and annually throughout childhood. This routine screening is recommended even when the child with Down syndrome passes the newborn hearing test.

Myringotomy with tympanostomy tube placement is the most common intervention for children, especially those with Down syndrome, who have experienced ETD that developed into chronic OM and CHL. Surgical candidacy for patients with Down syndrome does not differ from that of the general population and observation is initially recommended for middle ear effusion without hearing deficits. When stenosis of the EAC is present, tympanostomy tube placement may be delayed until the child is old enough for adequate manipulation of the tube in the ear canal, or a smaller tube maybe placed to resolve OM episodes with associated hearing loss. Longterm complications, such as tympanic membrane perforations and cholesteatoma are associated with the number of tympanostomy tube placements and chronicity of disease in patients with Down syndrome compared with age-matched children without Down syndrome.

Hearing aids have been proposed as an alternative therapy to tympanostomy tube placement in CHL, although no comparative trials have assessed outcomes in the population with Down syndrome. Bone-anchored hearing aids (BAHA) are also an option for patients with Down syndrome with CHL who cannot tolerate traditional hearing aids. The BAHA soft band is approved for patients less than 5 years old and has been shown to be associated with equivocal hearing and speech benefits in younger children when compared with normal BAHA and conventional hearing aids in older patients. In individuals more than 5 years old, BAHA is indicated for CHL, MHL, and single-sided deafness in both percutaneous and magnetic products. In the population with Down syndrome, BAHA implants have shown improved patient quality of life outcomes, higher patient and caregiver satisfaction rates, and no increased complication rates compared with the general population.

Early cochlear implantation is considered a surgical option for patients with Down syndrome and severe SNHL or single-sided deafness. Patients with Down syndrome require detailed diagnostic imaging to assess their candidacy for cochlear implant given the higher prevalence of otologic malformations. Additionally, development of speech progresses differently for patients with Down syndrome compared with typically developing children, regardless of cochlear implant placement, and caregivers should be made aware of this before surgery. Intensive and systematic rehabilitation through comprehensive care from knowledgeable practitioners, caregivers, and speech therapists can produce better postoperative outcomes.

Even with adequate hearing parameters, cognitive delay does not always explain the lack of correlation between speech and language measures in Down syndrome. Delayed and disordered speech will likely present in patients with Down syndrome before 3 years of age, but for many, the adverse effect present sooner owing to factors rooted in anatomy and motor control. While there are many hypotheses regarding orofacial characteristics and overall cognition associated with certain subtypes of Down syndrome, early engagement in speech therapy is paramount to preventing long-term communication problems.

Rhinosinusitis and Midface Anatomy

Patients with Down syndrome have many underlying anatomic factors that predispose them to nasal obstruction, rhinorrhea, and chronic rhinosinusitis, including midface hypoplasia with narrow nasal passages and hypoplastic sinuses, adenoid hypertrophy, andciliary dysfunction, and immune compromise. Radiographic studies have described abnormal frontal, maxillary, and sphenoid sinuses development ranging from hypoplasia to total nonpneumatization. Although many of these patients may be treated by a primary care physician, some will require surgical procedures, including adenoidectomy and endoscopic sinus surgery. Adenoid regrowth has been reported to be more common in patients with Down syndrome than the general population and should be considered as a source of infection even after adenoidectomy has been performed. Outcomes for endoscopic sinus surgery in the Down syndrome population have not been compared with the general population to date.

Sleep, Airway, and Swallowing Function

Obstructive Sleep Apnea

The most common reason for a consultation with an otolaryngologist among pediatric patients with Down syndrome is obstructive sleep apnea (OSA). The prevalence of OSA in children with Down syndrome may be as high as 80% vs 2% to 5% among the general pediatric population. The AAP recommends polysomnographic (PSG) screening for OSA detection in children with Down syndrome at 3 to 4 years of age. The risks of untreated OSA are well established in children, and include memory and cognitive impairment, as well as systemic medical comorbidities. Children with Down syndrome are already at a higher risk than the general population for pulmonary hypertension, and untreated OSA has been shown to increase that risk. Central sleep apnea and mixed sleep apnea have also been identified in this patient population, although neither is as prevalent as OSA. As patients with Down syndrome age, respiratory events during sleep become obstructive because of the narrowing of the upper airway.

Pediatric patients with Down syndrome have many anatomical risk factors for OSA. Adenotonsillar hypertrophy is common in these patients, as are craniofacial abnormalities including midface and mandibular hypoplasia, narrow nasopharynx, macroglossia, shortened palate, and lingual tonsil hypertrophy that may predispose them to upper airway obstruction. Patients with Down syndrome may also have generalized hypotonia that contributes to glossoptosis, hypopharyngeal collapse, and laryngomalacia. Furthermore, children with Down syndrome who are also obese are twice as likely as other children with Down syndrome to have OSA, which at baseline is more severe.

Adenotonsillectomy (AT) is the first-line treatment for children with Down syndrome and OSA. Positive airway pressure (PAP) therapy is an appropriate treatment alternative to surgery in patients with Down syndrome, especially children who are poor surgical candidates, have CSA, or who have persistent OSA after AT. Adherence to PAP usage can be a challenge, particularly at initiation of therapy.

Drug-induced sleep endoscopy (DISE) is indicated in persistent OSA for children with Down syndrome when considering further sleep surgery. In surgically naive children with Down syndrome, DISE has demonstrated greater overall obstruction, with higher rates of tonsillar, tongue base, and arytenoid collapse. Efficacy of DISE-directed surgery is mixed, with some studies demonstrating improvement in clinical and PSG outcomes and some showing little benefit. Lingual tonsillectomy and posterior midline glossectomy have demonstrated improvement in PSG parameters for children with Down syndrome and persistent OSA. Finally, tracheotomy may be necessary to provide PAP or ventilator support during sleep to some patients with severe OSA sequalae who have failed previous surgical or PAP therapy.

Hypoglossal nerve stimulator implants are an area of active investigation for pediatric patients with Down syndrome and OSA. The hypoglossal nerve stimulator (InspireMedicalSystems) is a surgically implantable device that uses a sensor electrode in the intercostal muscles and a stimulation lead around anterior branches of the hypoglossal nerve to deliver electrical impulses to tongue protrusio muscles during inspiration to alleviate tongue base obstruction during sleep. The device is well tolerated, and has been shown to improve PSG parameters and quality of life with a low adverse effect profile.

Adults with Down syndrome should be screened for PSG given the high prevalence of OSA and because self-reported symptoms are unreliable. For adults with Down syndrome, PAP is the cornerstone of treatment although compliance remains an issue, as it is with pediatric OSA. In those who need further treatment, the hypoglossal nerve stimulator implant has already been approved for all adults, including those with Down syndrome.

Airway Anomalies

Patients with Down syndrome have an increased incidence of comorbid airway anomalies, including laryngomalacia, laryngotracheal cleft, tracheomalacia, subglottic stenosis (congenital and acquired), tracheal stenosis, complete tracheal rings, and tracheal bronchus. Presenting symptoms may include stridor, dyspnea, cough, recurrent respiratory infections, aspiration, and/or cyanosis or apnea. The reported incidence of laryngomalacia in infants with Down syndrome is highly varied, estimated at 1% to as high as 50% in Down syndrome infants with respiratory symptoms. Laryngomalacia may persist beyond infancy because of hypotonia and gastroesophageal reflux.

Congenital subglottic stenosis, including an elliptical cricoid, is a common asymptomatic finding in children with Down syndrome. Care should be taken to intubate these pediatric patients with a smaller endotracheal tube. A higher incidence of prematurity and cardiac anomalies may necessitate intubation in infancy, which has been associated with a predisposition to acquired subglottic stenosis and posterior glottic stenosis.

The incidence of multilevel airway anomalies and need for tracheostomy or tracheoplasty are higher in the population with Down syndrome vs the general population. Mild to moderate tracheomalacia may be managed conservatively, but in severe cases defined by hospitalizations for recurrent respiratory infections and need for PAP or intubation, tracheobronchopexy, aortopexy, tracheal stenting, and/or tracheotomy procedure may be necessary.

Similarly, congenital tracheal stenosis was found to be the underlying cause of symptoms in 5% of patients with Down syndrome who were undergoing an operativeendoscopic procedure. The overall prevalence of symptomatic congenital vs acquired tracheal stenosis in patients with Down syndrome is estimated to be 0.4% and 0.8%, respectively.65Regarding decannulationafter tracheotomy, no difference was identified after laryngotracheal reconstruction in children with or without Down syndrome.

Complete tracheal rings is often associated with congenital heart disease and is treated with tracheal resection or slide tracheoplasty depending on the length and location of the stenosis. Tracheal surgical outcomes, such as tracheal resection and slide tracheoplasty, are worse among those with Down syndrome, and expectant management is appropriate when symptoms are mild

Swallowing Function

Children with Down syndrome are at increased risk of dysphagia and aspiration, which may persist into adulthood. Anatomic factors, such as shortened palate, macroglossia, dental anomalies, and airway anomalies as previously described along with functional deficits, including hypotonia and delayed development of oromotor function, increase the risk of an unsafe swallow in this population. Underlying immune deficiency in the setting of aspiration events may predispose patients with Down syndrome to greater risk of pneumonia and recurrent infections. Symptoms of poor feeding may include delayed suckling, problems with breast and bottle feeding, and desaturations. Unfortunately, individuals with Down syndrome have a high rate of silent aspiration.

Video fluoroscopic swallow studies (VFSS) have demonstrated abnormalities in swallow initiation, oral and pharyngeal phase dysphagia, aspiration, pharyngeal residual clearance, pharyngonasal reflux, and bolus formation among the population with Down syndrome.

Early referral to speech and language pathology services and screening for dysphagia aspiration using VFSS and functional endoscopic evaluation of swallow are vital in this population. Use of thickeners has been found to be more beneficial in children with dysphagia and Down syndrome, whereas a change in feeding system has been shown to be less helpful. Some children may require nasogastric feeds or gastrostomy tube placement, at least temporarily.

Although oromotor dysfunction with dysphagia has been reported in 31% to 80% of children with Down syndrome, the estimated prevalence in adults with Down syndrome is 25% to 30%. This decrease in prevalence with age may be explained by improvement in function and tone, although it is also possible that difficulties become hidden as children grow and learn to compensate and adapt. In addition to dysphagia, patients with Down syndrome have high rates of behavioral feeding difficulties, such as picky eating, slow rates of eating (a variant of obsessive-compulsive disorder), and rapid eating or food stuffing which predisposes to choking and asphyxiation.

Adults with Down syndrome are also prone to increased risk of aspiration and dysphagia associated with aging and the development of Alzheimer disease.

A confluence of characteristics common to Down syndrome may be associated with issues in the head and neck, from infancy through adulthood. Hearing concerns range from narrow ear canals and cerumen impactions to eustachian tube dysfunction, middle ear effusion, cochlear malformations, and conductive, sensorineural, and/or mixed hearing loss. Immune deficiency, hypertrophy of Waldeyer ring, and hypoplastic sinuses may complicate and develop into chronic rhinosinusitis. Speech delay, obstructive sleep apnea, dysphagia, and airway anomalies are also common among this patient population. Because these concerns may necessitate otolaryngologic surgery, it is vital for otolaryngologists to familiarize themselves with anesthetic concerns, including cervical spine instability, in patients with Down syndrome. Comorbid cardiac disease, hypothyroidism, and obesity may also affect these patients and otolaryngologic care.

Patients with Down syndrome may visit otolaryngology practices at all ages. It is important that otolaryngologists familiarize themselves with the common head and neck manifestations experienced by patients with Down syndrome. Knowing when to order screening tests is imperative to providing comprehensive care to this population of patients.

Source: Habib G. Zalzal, MD; Claire M. Lawlor, MD; JAMA Otolaryngol Head Neck Surg. doi:10.1001/jamaoto.2023.0001