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A 15-Year-Old Boy With Snoring and Molar Tooth SignA Boy With Snoring and Molar Tooth Sign FREE TO VIEW

Karim El-Kersh, MD; Egambaram Senthilvel, MD
Author and Funding Information

From the Department of Pulmonary, Critical Care and Sleep Disorders Medicine (Dr El-Kersh), and Division of Pediatric Sleep Medicine (Dr Senthilvel), University of Louisville, Louisville, KY.

CORRESPONDENCE TO: Karim El-Kersh, MD, Department of Pulmonary, Critical Care and Sleep Disorders Medicine, University of Louisville, Ambulatory Care Bldg, 550 S Jackson St, Louisville, KY 40202; e-mail: karim.elkersh@louisville.edu


Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details.


Chest. 2015;147(4):e148-e151. doi:10.1378/chest.14-1971
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A 15-year-old boy presented for evaluation of snoring and sleep-disordered breathing. The parents noted that the patient snored every night and that he had episodes when he stopped breathing, ending with gasping for air. He had no history of sleep walking, night terrors, tongue biting, or seizures. The patient had two healthy siblings, but he had a history of intellectual disability and developmental delay. The patient had a history of adenotonsillectomy.

Figures in this Article

The patient was afebrile with stable vital signs. BP was 130/70 mm Hg, heart rate was 95/min, height was 185 cm, and weight was 123 kg with a calculated BMI of 35 kg/m2. His general physical examination revealed intellectual disability, developmental delay, dysarthria, hypotonia, and gate disturbance. Cardiac and pulmonary examinations were within normal limits apart from periods of tachypnea precipitated by the physical examination attempts. These tachypneic episodes were sustained for a few minutes with a respiratory rate of ≥ 60/min. The episodes were not associated with sweating, wheezing, stridor, change in color, or desaturation. Head and neck examination revealed the presence of a high-arched palate, maxillary retrusion, and Mallampati class 4.

The patient underwent overnight polysomnography that showed an overall apnea-hypopnea index of 31 events/h of sleep (central apnea index, 9; obstructive apnea index, 2; obstructive hypopnea index, 20). Frequent central apnea events were noted, alternating with episodes of tachypnea (Fig 1). The patient was not receiving any narcotics, and his echocardiogram was normal. To uncover potential causes of central apnea, the patient underwent MRI of the brain that showed the molar tooth sign (MTS) (Fig 2).

Figure Jump LinkFigure 1 –  A 4-min polysomnographic recording during stage N2 non-rapid eye movement shows hypopnea (red arrow) and central apneas (black arrows) alternating with periods of tachypnea.Grahic Jump Location
Figure Jump LinkFigure 2 –  Brain MRI axial T2-weighted image shows the molar tooth sign, which results from elongated thickened superior cerebellar peduncles (arrows), deepened interpeduncular fossa (*), and cerebellar vermis hypoplasia.Grahic Jump Location
What is the diagnosis?
Diagnosis: Joubert syndrome associated with obstructive and central apnea

Joubert syndrome (JS) and related disorders are autosomal (rarely X-linked) recessive congenital disorders that share the obligatory hallmark of MTS, with an incidence of one in 100,000. The prevalence of JS may be underestimated because of the low awareness about the MTS. The MTS is a neuroradiologic sign comprising a triad of cerebellar vermis hypoplasia, elongated thickened superior cerebellar peduncles, and deepened interpeduncular fossa. This constellation of changes gives an appearance similar to a molar tooth, hence the name.

JS represents a spectrum of ciliopathies with underlying complex genetic mutations. Genetic defects associated with JS appear to be more prevalent in Ashkenazi Jews and Hutterites. So far, 21 causative genes have been identified. These mutant genes encode for mutant proteins that result in a defective structure of the primary cilia. These defective primary cilia lead to an impaired normal embryogenesis with resultant differing congenital anomalies associated with JS.

A diagnosis of JS and related disorders requires the presence of hypotonia, which can evolve into ataxia, developmental delay, and the neuroradiologic MTS. Cases fulfilling these primary criteria with no other organ involvement are termed pure JS, whereas other phenotypic variants exist depending on the involvement of the retina, kidneys, liver, and skeleton with some genotypic-phenotypic correlations.

Although respiratory abnormalities are considered a classic hallmark of JS, they are reported in only up to 71% of patients and, thus, are not a consistent finding. Respiratory abnormalities were initially believed to be precipitated by emotional excitement only during wakefulness, but evidence shows the presence of these abnormalities during sleep. The abnormal breathing pattern consists mainly of phases of tachypnea (up to 230 breaths/min) and apnea (up to 1 min) that predominate during non-rapid eye movement sleep and can give rise to a Cheyne-Stokes pattern of respiration. The prolonged apnea in neonates and infants can be potentially life threatening and may require ventilatory support. There are no longitudinal studies tracking the natural history of sleep-disordered breathing in patients with JS. The episodes of abnormal breathing are most likely caused by an abnormal central control of ventilation, which can be a reflection of brainstem involvement in these patients. Similar breathing patterns are reported with other conditions such as Dandy-Walker malformation and Rett syndrome, both of which lack the MTS.

Although little is known about sleep abnormalities in JS, it is estimated that the prevalence of sleep apnea in this syndrome is higher than the general pediatric population based on small studies in which up to 43% of pediatric sleep questionnaire responders had scores suggestive of a sleep-related breathing disorder. Sleep apnea in JS can be obstructive, central, or mixed. The hypotonia and facial abnormalities reported with this syndrome can predispose to the obstructive events, whereas CNS abnormalities may include the regulatory center of breathing in the lower pons and medulla, which can result in central apnea.

Treatment of sleep apnea in JS can be challenging because of the associated abnormal underlying respiratory pattern with phasic episodes of apneas and tachypnea. Episodes of prolonged tachypnea can be precipitated by positive airway pressure trials. Although there are minimal data available on how to manage sleep-disordered breathing in patients with JS, attended positive airway pressure titration studies should be performed to determine the best settings to eliminate the obstructive and central events. Bilevel spontaneous/timed mode or adaptive servoventilation may be needed to control the central apneas.

Clinical Course

The patient underwent trials of mask acclimatization with low CPAP pressure for about 4 weeks, but with every trial, his respiratory rate went up to ≥ 60/min (Fig 3). During the titration study, treatment-emergent central sleep apnea (complex sleep apnea) was observed. Neither the tested CPAP nor the bilevel positive airway pressure in spontaneous/timed mode completely resolved the obstructive and central events. At the bilevel positive airway pressure setting of 11/7 cm H2O and backup rate of 18 breaths/min, snoring was reduced, the apnea-hypopnea index was reduced to 9, and the oxygen saturation was maintained at > 88%.

Figure Jump LinkFigure 3 –  A 2-min polysomnographic recording during wakefulness shows tachypnea at 60 breaths/min.Grahic Jump Location

  • 1. CNS imaging is recommended to uncover potential causes of central sleep apnea events in pediatric patients.

  • 2. MTS is an obligatory hallmark for the diagnosis of JS.

  • 3. Evaluation for sleep-disordered breathing in patients with JS is recommended.

Financial/nonfinancial disclosures: The authors have reported to CHEST that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

Other contributions: CHEST worked with the authors to ensure that the Journal policies on patient consent to report information were met.

Maria BL, Boltshauser E, Palmer SC, Tran TX. Clinical features and revised diagnostic criteria in Joubert syndrome. J Child Neurol. 1999;14(9):583-590. [CrossRef] [PubMed]
 
Valente EM, Brancati F, Dallapiccola B. Genotypes and phenotypes of Joubert syndrome and related disorders. Eur J Med Genet. 2008;51(1):1-23. [CrossRef] [PubMed]
 
Wolfe L, Lakadamyali H, Mutlu GM. Joubert syndrome associated with severe central sleep apnea. J Clin Sleep Med. 2010;6(4):384-388. [PubMed]
 
Kamdar BB, Nandkumar P, Krishnan V, Gamaldo CE, Collop NA. Self-reported sleep and breathing disturbances in Joubert syndrome. Pediatr Neurol. 2011;45(6):395-399. [CrossRef] [PubMed]
 
Romani M, Micalizzi A, Valente EM. Joubert syndrome: congenital cerebellar ataxia with the molar tooth. Lancet Neurol. 2013;12(9):894-905. [CrossRef] [PubMed]
 

Figures

Figure Jump LinkFigure 1 –  A 4-min polysomnographic recording during stage N2 non-rapid eye movement shows hypopnea (red arrow) and central apneas (black arrows) alternating with periods of tachypnea.Grahic Jump Location
Figure Jump LinkFigure 2 –  Brain MRI axial T2-weighted image shows the molar tooth sign, which results from elongated thickened superior cerebellar peduncles (arrows), deepened interpeduncular fossa (*), and cerebellar vermis hypoplasia.Grahic Jump Location
Figure Jump LinkFigure 3 –  A 2-min polysomnographic recording during wakefulness shows tachypnea at 60 breaths/min.Grahic Jump Location

Tables

Suggested Readings

Maria BL, Boltshauser E, Palmer SC, Tran TX. Clinical features and revised diagnostic criteria in Joubert syndrome. J Child Neurol. 1999;14(9):583-590. [CrossRef] [PubMed]
 
Valente EM, Brancati F, Dallapiccola B. Genotypes and phenotypes of Joubert syndrome and related disorders. Eur J Med Genet. 2008;51(1):1-23. [CrossRef] [PubMed]
 
Wolfe L, Lakadamyali H, Mutlu GM. Joubert syndrome associated with severe central sleep apnea. J Clin Sleep Med. 2010;6(4):384-388. [PubMed]
 
Kamdar BB, Nandkumar P, Krishnan V, Gamaldo CE, Collop NA. Self-reported sleep and breathing disturbances in Joubert syndrome. Pediatr Neurol. 2011;45(6):395-399. [CrossRef] [PubMed]
 
Romani M, Micalizzi A, Valente EM. Joubert syndrome: congenital cerebellar ataxia with the molar tooth. Lancet Neurol. 2013;12(9):894-905. [CrossRef] [PubMed]
 
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