Obstructive sleep apnoea in Treacher Collins syndrome: prevalence, severity and cause


This cohort study in 35 patients (13 children) evaluates the prevalence, severity and anatomical cause of obstructive sleep apnoea syndrome (OSAS) in patients with Treacher Collins syndrome. Ambulatory polysomnography was performed cross-sectionally to determine OSAS prevalence and severity. All upper airway related surgical interventions were evaluated retrospectively. In 11 patients, sleep endoscopy, and flexible and rigid endoscopy were applied to determine the level of anatomical obstruction of the upper airway. The overall prevalence of OSAS in Treacher Collins patients was 46% (54% in children; 41% in adults). Thirty-eight upper airway related surgical interventions were performed in 17 patients. Examination of the upper airway revealed various anatomical levels of obstruction, from the nasal septum to the trachea. Most significant obstruction was found at the level of the oro/hypopharynx. OSAS in Treacher Collins patients is an important problem so all patients should be screened for OSAS by polysomnography. Endoscopy of the upper airways was helpful in determining the level of obstruction. Surgical treatment at one level will not resolve OSAS in most patients because OSAS in Treacher Collins has a multilevel origin. Non-invasive ventilation (continuous positive airway pressure or bilevel positive airway pressure) or tracheotomy should be considered as a treatment modality.

Treacher Collins syndrome (TCS) is a rare congenital craniofacial condition. Its deformities can range from a slight defect of the cilia to severe defects such as micrognatia and zygomaticotemporomaxillary dysostosis. Mandibular hypoplasia, choanal atresia, underdevelopment of the auricles, a downslant of the eyelids, coloboma of the eyelids and hypoplasia of the zygomatic bone and lateral orbital wall are common features of this condition. TCS is an autosomal dominant disorder with an incidence of 1 in 50,000 live births. In more than 60% of cases there is no previous family history and the condition is thought to arise as the result of a de novo mutation. TCS is mainly caused by mutations in the TCOF1 gene, located on chromosome 5, which encodes a low complexity, serine/alanine-rich, nucleolar phosphoprotein known as treacle. Deletions, insertions, splicing, and missense and nonsense mutations in the TCOF1 gene cause TCS, however alterations in the POLR1D and POLR1C genes have also been demonstrated to cause TCS. Patients with craniofacial syndromes, such as Pierre Robin sequence, Apert, Crouzon and Pfeiffer syndrome, frequently suffer from obstructive sleep apnoea syndrome (OSAS).

The main factors that lead to OSAS in craniofacial syndromes appear to be midface and/or mandibular hypoplasia. Mandibular hypoplasia may result in a posterior collapse of the tongue base and a decreased oropharyngeal airway. Leaving OSAS untreated may result in major physical and functional impairment due to the disturbed sleep patterns. TCS is a syndrome in which mandibular hypoplasia is a frequent finding, but only a few studies suggest that TCS may be accompanied by sleep apnoea. These studies are case reports, with the exception of the study by Sher et al. published in 1986. They found a prevalence of 25% in a small group of TCS patients using OSAS criteria that differ from the current standards; they did not differentiate between paediatric and adult TCS patients.

It is important to establish the prevalence and severity of OSAS in TCS patients because of its potential long-term physical and functional effects; but this knowledge is currently lacking. The present study determined these factors in a large group of TCS patients, taking into account all respiratory related interventions that the patients had undergone.

Materials and methods

This cohort study comprised cross-sectional and retrospective parts and was conducted in a population diagnosed with TCS and treated by the multidisciplinary craniofacial team at the Erasmus MC since 1975 (over 36 years). All patients were eligible for inclusion if they were diagnosed with TCS within that period. The research protocol was approved by the Ethical Committee of the Erasmus MC (MEC-2008-402).

Patients were contacted by mail or approached personally at a regular appointment in the outpatient clinic. They had to decide whether to participate within 1 month. Patients were contacted at home by telephone if they had not responded to the mail within that period.

Between January 2007 and November 2009 all included patients underwent a nightly ambulatory polysomnography (PSG) for clinical and/or research purposes. Patients were divided into a paediatric group and an adult group based on their age at the time of the PSG; there was no overlap between the two groups. With the use of a paediatric and an adult group (cut-off at age >18 years) the authors were able to determine the proportion of patients suffering from OSAS in both groups separately. PSG was carried out with the Embletta Portable Diagnostic System and analysed with Somnologica for Embletta software 3.3 ENU (Medcare Flaga, Reykjavik, Iceland). Cardiorespiratory variables were measured in the clinical or home setting. Respiratory variables measured were nasal airflow, chest and abdominal wall motion, snoring, oxygen saturation, and oximeter pulse waveform. The minimal total registration time was 6 h. Analysis of the PSG was expressed in the apnoea-hypopnoea index (AHI) and the oxygenation-desaturation index (ODI). AHI was defined by the number of obstructive apnoeas and hypopnoeas per hour. ODI was defined by the number of desaturations (≥4% decrease with respect to the baseline oxygen saturation during 10 s) per hour. An obstructive apnoea was defined as a cessation of airflow referred to baseline airflow signal, during at least 10 s or less if followed by desaturation. A hypopnoea was defined as a reduction in airflow of 50% referred to baseline airflow signal, during at least 10 s or less if followed by desaturation.

For children, the obstructive-AHI (OAHI) was used. Central apnoeas were not included. An OAHI score <1 was considered normal for children, 1–5 was defined as mild OSAS, 5–24 as moderate OSAS, and a score >24 as severe OSAS. The duration of obstructive apnoea and hypopnoea was defined as ‘longer than two breaths’. ODI scores were taken into account, but not for diagnostic differentiation between grades of severity of OSAS in children.

For adults, the current OSAS guideline standards for adults were used. OSAS was diagnosed when AHI fell outside the normal limit (AHI >5). An AHI of 5–15 was defined as mild OSAS, 15–30 as moderate OSAS, and an AHI >30 was defined as severe OSAS.

Regarding upper airway surgery, a retrospective chart review was performed on upper-airway-related surgery in all patients. Surgery performed in other medical centres was also taken into account. All available PSGs and the presence of a tracheotomy or use of continuous positive airway pressure (CPAP) for severe OSAS were taken into account. Types of surgeries were categorized according to the level of the upper airway.

Regarding sleep endoscopy and the level of obstruction in TCS with OSAS, data on drug-induced sleep endoscopy were taken into account for patients suffering from severe OSAS to assess the anatomical site of obstruction during sleep. The jaw-thrust manoeuvre was applied to check whether the obstruction could be alleviated. If available, results from flexible and rigid endoscopy were taken into account. Plain lateral skull radiographs for cephalometric analysis were taken to determine the severity of the mandibular/maxillary hypoplasia.

Statistical analysis

All statistics concern descriptive numerical and categorical data. Measured values are reported as mean ± 1 standard deviation (SD) or median (range), as appropriate. Outcomes of PSGs are expressed as median and interquartile range. Analyses were made using SPSS 17.0 for Windows (SPSS, Inc., Chicago, IL, USA).



From 1974 to 2010, 58 patients were diagnosed with TCS. In this period four patients died: three suffered from severe OSAS, two deaths were not related to OSAS, and the cause of death was unknown for one patient. The death of one patient was related to OSAS because of asphyxiation due to frequent aspiration. Of the 54 patients, 19 did not participate due to emigration (1 patient), lack of correct personal details (3 patients), unwillingness to participate (14 patients), and loss to follow-up (1 patient). At least two patients who refused to participate suffered from severe OSAS (one tracheotomy, and one used CPAP). Another patient who was lost to follow-up was known to have a tracheotomy for severe OSAS.

Thirty-five of the 54 patients (65%) were included in this study. At time of the inclusion this group comprised 13 children (5 boys) and 22 adults (10 males). Median age of the paediatric group was 12 years (range 0–17 years) and for the adult group, 37 years (range 20–60 years). The median body mass index of the adult group was 20.7 (15.2–29.4), and was 17.4 (11.0–20.5) in the paediatric group.


A PSG was performed in 12 children and showed OSAS in 6 of them. No PSG was performed in 1 child who required instant treatment (tracheotomy) for severe OSAS; because temporary closure of the cannula caused immediate breathing problems, decannulation was impossible. This patient was therefore classified as having severe OSAS without undergoing a formal assessment. Seven of the 13 children (54%) had OSAS: 1 mild, 5 moderate and 1 severe ( Table 1 ). Five of the 13 children (38%) had undergone airway treatment prior to these measurements.

Table 1
Cross-sectional polysomnography outcomes in paediatric and adult TCS patients ( n = 35).
Prevalence No OSAS Mild OSAS Moderate OSAS Severe OSAS Total
TCS children ( n = 13) 46% (6/13) 8% (1/13) 38% (5/13) 8% (1/13) * 54% (7/13) **
Median OAHI (interquartile range) n/a 0.9 (–) 5.4 (5.2–11.0)
Median ODI (interquartile range) n/a 1.9 (–) 8.3 (0.3–20.2)
TCS adults ( n = 22) 59% (13/22) 14% (3/22) 0% (0/22) 27% (6/22) 41% (9/22) **
Median AHI (interquartile range) n/a 9.0 (9.0–14.0) 55.0 (54.0–111)
Median ODI (interquartile range) n/a 4.0 (2.0–6.0) 28.5 (14.5–38.75)
Total ( n = 35) 54% (19/35) 11% (4/35) 14% (5/35) 20% (7/35) 46% (16/35) **
n/a: not applicable.

* No PSG was performed in one child who required instant treatment (tracheotomy) for severe OSAS. Because temporary closure of the cannula immediately caused severe breathing problems this patient was classified as having severe OSAS, without undergoing formal assessment.

** Twelve of the 22 adults and 5 of the 13 children underwent airway surgery prior to the PSG.

A PSG was performed in all 22 adults; OSAS was diagnosed in 9 (41%). Mild OSAS was diagnosed in 3 patients and severe OSAS in 6 patients ( Table 1 ). Of these 22 adults, 12 had undergone airway treatment (55%) prior to these measurements.

Upper airway surgical procedures in TCS

In 17 (49%) of the 35 TCS patients 38 interventions related to the upper airway were performed. Figure 1 shows the follow-up process.

Fig. 1
Follow-up of TCS patients: time at polysomnography, severity of OSAS, all forms of invasive or non-invasive airway treatment, endoscopies and X-rays are presented together with the obstruction levels. MDO, mandibular distraction osteogenesis; MRD, mandibular repositioning device; PSG, polysomnography; SARME, surgically assisted rapid maxillary expansion; TMD, transmandibular distractor.
Symbols used: ( ) OSAS diagnostic evaluation moment, (|) surgical intervention and (♢) obstruction level evaluation moment.

A tracheotomy was performed in two of the newborn infants because of severe upper airway obstruction. One of these patients has now reached adulthood and has been successfully decannulated.

Nasal surgery was performed in three patients (two in childhood) aged 5, 17 and 49 years at the time of intervention. Two patients suffered from severe OSAS preoperatively. In the adult patient the distinct septum deviation was surgically corrected, resulting in a reduction of apnoeas of 224 to 3 per/h during the night ( Fig. 1 : no. 7) ( Table 2 : no. 7). In 1 paediatric patient (with severe OSAS preoperatively), surgery for choanal atresia at 5 years of age resulted in moderate OSAS postoperatively.

Table 2
Levels of obstruction found in the upper respiratory tract in 10 patients with Treacher Collins syndrome.
Levels of obstruction in the upper respiratory tract including the diagnostic tools used
Level of obstruction Paediatric cases Adult cases
No. 1 No. 2 No. 3 No. 5 No. 7 No. 8 No. 9 No. 10 No. 11 No. 12
Choana Rigid Flex
Septum Flex Flex
Nasopharynx * Rigid
Maxilla X-ray X-ray X-ray
Adenoid Flex
Palate Sleep
Oro/hypopharynx Flex Sleep Flex
Glossoptosis Flex Sleep Sleep Sleep
Hypoplastic mandible X-ray X-ray X-ray
Pharynx * Rigid Flex Flex Sleep
Epiglottis Sleep
Larynx Flex Rigid Flex Flex
Trachea Rigid
Only gold members can continue reading. Log In or Register to continue

Jan 26, 2018 | Posted by in Oral and Maxillofacial Surgery | Comments Off on Obstructive sleep apnoea in Treacher Collins syndrome: prevalence, severity and cause
Premium Wordpress Themes by UFO Themes