Craniosynostosis affects the majority of mucopolysaccharidosis patients and can contribute to increased intracranial pressure.

BACKGROUND: The mucopolysaccharidoses are multisystem lysosomal storage diseases characterized by extensive skeletal deformities, including skull abnormalities. The objective of this study was to determine the incidence of craniosynostosis in the different mucopolysaccharidosis (MPS) types and its clinical consequences. METHODS: In a prospective cohort study spanning 10 years, skull imaging and clinical evaluations were performed in 47 MPS patients (type I, II, VI, and VII). A total of 215 radiographs of the skull were analyzed. The presence and type of craniosynostosis, the sutures involved, progression over time, skull shape, head circumference, fundoscopy, and ventriculoperitoneal shunt (VPS) placement data were evaluated. RESULTS: Craniosynostosis of at least one suture was present in 77% of all 47 MPS patients (≤ 6 years of age in 40% of all patients). In 32% of all MPS patients, premature closure of all sutures was seen (≤ 6 years of age in 13% of all patients). All patients with early closure had a more severe MPS phenotype, both in the neuronopathic (MPS I, II) and non-neuronopathic (MPS VI) patient groups. Because of symptomatic increased intracranial pressure (ICP), a VPS was placed in six patients, with craniosynostosis as a likely or certain causative factor for the increased pressure in four patients. One patient underwent cranial vault expansion because of severe craniosynostosis. CONCLUSIONS: Craniosynostosis occurs in the majority of MPS patients. Since the clinical consequences can be severe and surgical intervention is possible, skull growth and signs and symptoms of increased ICP should be monitored in both neuronopathic and non-neuronopathic patients with MPS.

Sleep Architecture Linked to Airway Obstruction and Intracranial Hypertension in Children with Syndromic Craniosynostosis.

BACKGROUND: Children with syndromic craniosynostosis often have obstructive sleep apnea and intracranial hypertension. The authors aimed to evaluate (1) sleep architecture, and determine whether this is influenced by the presence of obstructive sleep apnea and/or intracranial hypertension; and (2) the effect of treatment on sleep architecture. METHODS: This study included patients with syndromic craniosynostosis treated at a national referral center, undergoing screening for obstructive sleep apnea and intracranial hypertension. Obstructive sleep apnea was identified by polysomnography, and categorized into no, mild, moderate, or severe. Intracranial hypertension was identified by the presence of papilledema on funduscopy, supplemented by optical coherence tomography and/or intracranial pressure monitoring. Regarding sleep architecture, sleep was divided into rapid eye movement or non-rapid eye movement sleep; respiratory effort-related arousals and sleep efficiency were scored. RESULTS: The authors included 39 patients (median age, 5.9 years): 19 with neither obstructive sleep apnea nor intracranial hypertension, 11 with obstructive sleep apnea (four moderate/severe), six with intracranial hypertension, and three with obstructive sleep apnea and intracranial hypertension. Patients with syndromic craniosynostosis, independent of the presence of mild obstructive sleep apnea and/or intracranial hypertension, have normal sleep architecture compared with age-matched controls. Patients with moderate/severe obstructive sleep apnea have a higher respiratory effort-related arousal index (p < 0.01), lower sleep efficiency (p = 0.01), and less rapid eye movement sleep (p = 0.04). An improvement in sleep architecture was observed following monobloc surgery (n = 5; rapid eye movement sleep, 5.3 percent; p = 0.04). CONCLUSIONS: Children with syndromic craniosynostosis have in principle normal sleep architecture. However, moderate/severe obstructive sleep apnea does lead to disturbed sleep architecture, which fits within a framework of a unifying theory for obstructive sleep apnea, intracranial hypertension, and sleep. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, II.

How does obstructive sleep apnoea evolve in syndromic craniosynostosis? A prospective cohort study.

OBJECTIVE: To describe the course of obstructive sleep apnoea syndrome (OSAS) in children with syndromic craniosynostosis. DESIGN: Prospective cohort study. SETTING: Dutch Craniofacial Centre from January 2007 to January 2012. PATIENTS: A total of 97 children with syndromic craniosynostosis underwent level III sleep study. Patients generally undergo cranial vault remodelling during their first year of life, but OSAS treatment only on indication. MAIN OUTCOME MEASURES: Obstructive apnoea-hypopnoea index, the central apnoea index and haemoglobin oxygenation-desaturation index derived from consecutive sleep studies. RESULTS: The overall prevalence of OSAS in syndromic craniosynostosis was 68% as defined by level III sleep study. Twenty-three patients were treated for OSAS. Longitudinal profiles were computed for 80 untreated patients using 241 sleep studies. A mixed effects model showed higher values for the patients with midface hypoplasia as compared to those without midface hypoplasia (Omnibus likelihood ratio test=7.9). In paired measurements, the obstructive apnoea-hypopnoea index (Z=-3.4) significantly decreased over time, especially in the first years of life (Z=-3.3), but not in patients with midface hypoplasia (Z=-1.5). No patient developed severe OSAS during follow-up if it was not yet diagnosed during the first sleep study. CONCLUSIONS: OSAS is highly prevalent in syndromic craniosynostosis. There is some natural improvement, mainly during the first 3 years of life and least in children with Apert or Crouzon/Pfeiffer syndrome. In the absence of other co-morbid risk factors, it is highly unlikely that if severe OSAS is not present early in life it will develop during childhood. Ongoing clinical surveillance is of great importance and continuous monitoring for the development of other co-morbid risk factors for OSAS should be warranted.

Screening for obstructive sleep apnea in Treacher-Collins syndrome.

OBJECTIVES/HYPOTHESIS: This study evaluated the accuracy of established obstructive sleep apnea syndrome (OSAS) questionnaires based on presenting symptoms and complaints as screening tools for OSAS in Treacher-Collins syndrome (TCS). STUDY DESIGN: Cross-sectional cohort study. METHODS: In 35 TCS patients (13 children, 22 adults) in whom diagnostic polysomnographic results on OSAS were available, the Brouillette score was evaluated in children and the Epworth Sleepiness Scale in adults. RESULTS: The total Brouillette score showed a sensitivity of 50%, specificity of 71%, and positive and negative predictive values of 60% and 63%, respectively. The answer "No" to the question as to whether a child snored could rule out OSAS in children, and showed positive and negative predictive values of 55% and 100%, respectively. The Epworth Sleepiness Scale showed a sensitivity of 0%, specificity of 92%, and positive and negative predictive values of 0% and 57%, respectively. A positive answer to the question of whether a person falls asleep while sitting and talking to someone (sometimes or more) was able to predict OSAS in adults; this question had positive and negative predictive values of 100% and 72%, respectively. CONCLUSIONS: This cross-sectional cohort study showed that the Brouillette score and the Epworth Sleepiness Scale are of minimal usefulness in TCS. Diagnosis of OSAS based solely on complaints is not reliable, probably due to habituation. Therefore, for a good evaluation and optimal multidisciplinary treatment of this chronic disease in TCS, all newly referred pediatric and adult TCS patients should be screened for OSAS at least once with polysomnography.