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Breathing Related Sleep Disorders in Rubinstein-Taybi Syndrome
Raour Amin, M.D.
Pulmonary Medicine
Children's Hospital Medical Center
Cincinnati, Ohio
Introduction:
Rubinstein-Taybi Syndrome (RTS) is a rare multiple congenital anomalysyndrome characterized by a pattern of malformation that includes typical facial dysmorphic features, small
stature, broad thumbs and toes, and mentalretardation (1). Studies have shown that breathing disturbances occur in11% of subjects with RTS (2). The clinical history and the characteristiccraniofacial
malformations indicate that the nature of breathing disturbances in TRS is related to airway obstruction during sleep. Thefollowing section explains how craniofacial malformation in RTS predisposes to
the development of airway obstruction during sleep.
The major goal of the respiratory control system during wakefulness and sleep is a homeostatic one: to keep blood gases in a range that allows the metabolic functions of the body
to remain normal. Disturbances of breathing during sleep such as sleep apnea can disrupt the normal body homeostasis and adversely affect the function of other organs. The changes in breathing
patterns during sleep, which might be inconsequential in normal subjects may contribute to sleep apnea in children and adults with craniofacial malformations such as in RTS. Specifically the decrease in
upper airway muscle tone during rapid eye movement sleep (REM) increases the risk for upper airway closure. Sleep apnea is defined as cessation of airflow at the nose and mouth. When no respiratory
effort is present the event is termed central apnea., If respiratory effort persists despite cessation of airflow the event is termed obstructive apnea. Central apnea results predominantly from
disturbance of the control of respiration during sleep, while obstructive apnea is a result predominantly from disturbances of mechanisms that maintain the patency of the pharyngeal airway during sleep.
Obstructive Sleep Apnea (OSA):
Obstructive sleep apnea is characterized by recurrent closure of the pharyngeal airway during sleep. Although the exact mechanisms of obstructive sleep apnea are not
completely understood, there is wide agreement that upper airway patency during sleep is determined by a balance of forces that tend to collapse the airway and forces that tend to maintain the upper airway
open.
Determinants of Upper Airway Patency During Sleep:
The pharyngeal airway is a collapsible tube that lacks bony or cartilgenous structures to maintain its patency. The inspiratory phase of respiration is associated with
a reduction in the pressure in the lumen of the airway leading to a decrease in the pharyngeal cross-section. The upper airway
dilating muscles, which provide intrinsic stiffness to the pharyngeal
wall, act during inspiration to minimize the pharyngeal narrowing induced by negative intraluminal pressure (3). The compliance of the pharyngeal wall, which reflects the degree of stiffness of the airway,
modulates the collapsing effects of the negative intraluminal pressure. Studies have shown that the pharynx becomes more collapsible as it narrows (4). There is also compelling evidence that
patients with obstructive sleep apnea have a smaller pharyngeal airway relative to normal subjects (5). It is therefore evident that airway size is an important determinant of the patency of the upper
airway during sleep. The smaller the size of the airway the easier it is for the airway to collapse. The patency of the upper airway however, does not depend exclusively on the size and compliance of
the pharynx. Other factors such as the adhesive forces of the mucosa (6), changes in the vascular tone of the blood vessels supplying the airway (7) and central ventilatory control may also play an important
role in maintaining airway patency during sleep (8).
Craniofacial Structures:
The face in (RTS) shows striking age related change. The telltale signs of the syndrome become accentuated with age. Microcephaly with concomitant reduction in head
width and length are present across all age groups from infancy to adulthood. There is also narrowing at the skull base, and relative broadening across the brows and the lower face. Upper facial,
mid-facial, and lower facial depth are also reduced (9). Although there has been no study that radiographically examined the size of the pharyngeal airway in RTS, the reduced width and depth of the face
suggest that the
cross section area of the pharynx is smaller relative to normal. Otolaryngological examination of the upper airway in RTS shows redundant mucosal folds of the lateral and posterior
pharyngeal wall, which further contribute to airway obstruction (10).
Additional Factors Which Contribute to Upper Airway Obstruction During Sleep
in RTS:
Although the pharynx is the predominant site of obstruction in subjects with OSA, obstruction at any level along the upper airway increases the degree of severity of sleep apnea.
Nasal obstruction due to narrowing of nasal passages has been described in RTS. Deviated nasal septum has been reported to occur in up to 71% of subjects with RTS. Abnormalities of the size and
placement of the mandible occurs in 48% of cases, while micrognathia defined as small size mandible, occurs in 49% of cases (2). Hypertrophy of the tonsils and adenoids further compromise the size of the
airway and increase the severity of upper airway obstruction. Obesity can play an important role in the fat infiltration of upper airway structures with consequent mucosal hypertrophy and obstruction to
air passage during sleep (11).
Clinical Presentation of Obstructive Sleep Apnea:
OSA presents with nighttime as well as daytime symptoms. William Osler has described the nighttime symptoms in 1892. "At night the child's sleep is greatly
disturbed, the respirations are loud and snorting, and there are prolonged pauses, followed by deep noisy, inspirations."
Snoring is present in 97% of subjects with OSA, respiratory pauses and restless sleep are present in 78% of cases. Subjects with OSA tend to sweat excessively during their
sleep. Bed-wetting occurs in 8% of children with OSA. There is a high prevalence of odd sleep position in children with OSA. Sleeping with the neck hyperextended, kneeling in knee chest position,
sleeping on propped up pillows and sitting upright occurs in up to 65% of children with OSA.
William Osler has also described the daytime symptoms of obstructive sleep apnea in 1892. "The expression is dull, heavy, and apathetic. In longstanding cases the child
responds slowly to questions, and may be sullen and cross. Among other symptoms may be mentioned headache, general listlessness, and an indisposition for physical and mental exertion."
On awakening from sleep, subjects with OSA have more frequent complaints of headaches, grogginess and dry mouth. Excessive daytime sleepiness has been reported in 8% to 85% of
children with OSA. Impaired school performance, speech defect, hyperactivity and attention deficit syndrome have also been linked to OSA. It is important, however to emphasize that the effect of
OSA on daytime behavior has yet to be proven. Gastrointestinal symptoms such as nausea, vomiting, swallowing difficulties, poor weight gain, and poor appetite are more prevalent in children with OSA
relative to normal control. Symptoms of heart failure usually manifest in longstanding and severe degreeof OSA (12).
Management of Obstructive Sleep Apnea:
Careful history and physical examination are the first steps in the evaluation of patients suspected of having OSA. An overnight polysomnography is essential in confirming the
diagnosis of OSA and in determining the degree of its severity. Given the multiple factors which could worsen the degree of airway obstruction in RTS, it is important that the management be tailored to
each individual. Identification of all the factors contributing to airway obstruction is essential. Cephalometric and Otolaryngological examinations including upper airway endoscopy and airway
fluoroscopy could be of value in determining the site of airway obstruction. It is also important to determine whether obesity contributes to airway obstruction and implement a plan for weight loss. The
management of obstructive sleep apnea consists of medical and surgical interventions. The medical management includes nasal steroids, weight loss for obese subjects, and continuous positive airway
pressure (CPAP). The most commonly performed surgical procedure is the removal of adenoids and tonsils. Other surgical techniques have proven to be of value in the management of OSA in adults.
Further studies are needed to delineate the role of surgical management of OSA in children with craniofacial abnormalities such as RTS.
Reference List
1. Kenneth Lyons J (ed). Rubinstein-Taybi Syndrome. Smith's Recognizable
Patterns of Human Malformation, ed 4, 84-87. 1988.
2. Hennekam RC, van den Boogaard MJ, Sibbles BJ, Van Spijker HG.
Rubinstein-Taybi syndrome in The Netherlands. American Journal of Medical
Genetics - Supplement 1990;6:17-29.
3. Remmers JE, de Groot WJ, Sauerland EK et al. Pathogenesis of airway
occlusion during sleep. J Appl. Physiol 44:931-938. 1978.
4. Kryger MH, Roth T, Dement WC eds. Anatomy and physiology of upper airway
obstruction. Principles and Practice of Sleep Medicine, 632-656. 1994.
5. Schwab RJ, Gefter WB, Hoffman EA, Gupta KB, Pack AI. Dynamic upper
airway imaging during awake respiration in normal subjects and patients with
sleep disordered breathing. Am. Rev. Respir. Dis. 1993. Nov. 148:1385-400.
6. Van der Touw, Crawford ABH, Wheatly JR. Effects of a synthetic lung
surfactant on pharyngeal patency in awake human subjects. J Appl. Physiol
82, 78-85. 1997.
7. Wasicko JJ, Hutt DA, Parisi RA et al. The role of the vascular tone in
the control of upper airway collapsibility. Am Rev. Respir. Dis. 141,
1569-1577. 1990.
8. Onal E, Burrows DL, Hart RH, Lopata M. Induction of periodic breathing
during sleep causes upper airway obstruction in humans. J Appl. Physil
1986; 61(4):1438-43.
9. Allanson JE, Hennekam RC. Rubinstein-Taybi syndrome: objecive
evaluation of craniofacial structure. American Journal of Medical Genetics
1997; 71(4):414-9.
10. Zucconi M, Ferini-Strambi L, Erminio C, Pestalozza G, Smirne S.
Obstructive sleep apnea in the Rubinstein-Taybi syndrome. Respiration 1993;
60(2):127:32.
11. Horner RL, Mohiaddin RH, Lowell DG, Shea SA, Burman ED, Longmore DB, Guz
A. Sites and sizes of fat deposits around the pharynz in obese patients
with obstructive sleep apnea and weight matched controls. European
Respiratory Journal 1989; 2(7):613:22.
12. Brouillette RT, Fernback SK, Hunt CE. Obstructive sleep apnea in
infants and children. Journal of Pediatrics 1982; 100(1):31:40.
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