Journal of Sleep Disorders: Treatment and CareISSN: 2325-9639

Case Report, J Sleep Disor Treat Care Vol: 7 Issue: 1

Severe Obstructive Sleep Apnea in a Patient with Fragile X Syndrome

Mashaqi S* and Johnson K

Department of pulmonary, critical care and sleep medicine, Sanford Health - University of North Dakota, Grand Forks, USA

*Corresponding Author : Mashaqi S
Sanford Sleep Center– University of North Dakota, 2801 University Dr. S Fargo, ND 58104, USA
[email protected]

Received: July 31, 2017 Accepted: February 20, 2018 Published: March 04, 2018

Citation: Mashaqi S, Johnson K (2018) Severe Obstructive Sleep Apnea in a Patient with Fragile X Syndrome. J Sleep Disor: Treat Care 7:1. doi: 10.4172/2325-9639.1000206


Fragile X Syndrome (FXS) is a common disorder associated with intellectual disability. It is a multi-systemic disorder (e.g. cardiac, neurological, growth, gastrointestinal, ocular and congenital). It is also associated with many psychiatric features (anxiety, autism spectrum disorder, attention and aggression). Sleep disorders tend to occur at a higher prevalence in patients with FXS (e.g. insomnia and obstructive sleep apnea). This case reports severe obstructive sleep apnea in a patient with FXS that was treated successfully with PAP therapy and lead to the improvement of several medical and psychiatric symptoms.

Keywords: Fragile X syndrome; Obstructive sleep apnea; Polycythemia; Positive airway pressure; Hypoxia, Seizure


FXS: Fragile X Syndrome; OSA: Obstructive Sleep Apnea; APAP: Automated Positive Airway Pressure; AHI: Apnea Hypopnea Index; ASD: Autism Spectrum Disorder; REM: Rapid Eye Movement


Fragile X syndrome is a genetic disorder which results from expansion mutation of a CGG repeat sequence with subsequent reduction in the gene product “Fragile X mental retardation protein”. The absence of this protein results in many morphological features, intellectual disabilities, cognitive dysfunction and many other systemic features. It is more common in boys. The prevalence of FXS is estimated to be 1:5,000-7,000 males and 1: 4,000-6,000 females. It is the second leading cause of intellectual disability after Down syndrome1. Patients with FXS appear to be at higher risk of developing sleep related breathing disorders. Our case reports a patient with FXS who presents with a severe degree of obstructive sleep apnea (OSA).

Case Report

The patient is a 26 year old white male patient with a history of fragile X syndrome (FXS). He presented to the hematology and pulmonary clinics with polycythemia. The work up for hematological neoplasms was negative. He had an overnight pulse oximetry that showed nocturnal oxygen desaturation and a pattern that is suggestive of sleep related breathing disorders (Figure 1). Subsequently, he was referred to sleep medicine.

Figure 1: Overnight pulse oximetry on room air showing a “saw tooth pattern” that is highly suggestive of obstructive sleep apnea.

The patient presented with excessive daytime sleepiness. He lives in a special needs residential facility and was told by his friends that he dozes off and looks very sleepy in the morning. His routine sleep schedule consists of bedtime at 9:30 PM and wake up time at 6:20 AM. The patient denied insomnia of sleep initiation or maintenance. He denied morning headache. His mother witnessed loud snoring and apnea episodes. He denied any symptoms of restless legs syndrome. He does have a family history of obstructive sleep apnea. He underwent tonsillectomy and adenoidectomy. His past medical history includes seizure which is controlled with medications.

Physical exam showed a long and narrow face with prominent forehead, high arched palate, severe retrognathia, Mallampati scale IV. Neck circumference was 15 inches and a body mass index of 25 kg/m2 [1]. The rest of the physical exam was normal.

His laboratory tests at presentation showed Hgb 20.5 g/dl, RBC 6.11 M/Ul, Hct 56.9%. Hemoglobin electrophoresis was within normal limits, erythropoietin level was 11.4 mIU/ml which is within normal limits. Bone marrow biopsy showed a mildly hypocellular bone marrow with unremarkable hematopoiesis. Flow cytometry showed normal B and T lymphocytes with no monoclonal B lymphoid population.

The patient underwent overnight polysomnography and CPAP titration studies (Figure 2) which showed a severe degree of obstructive sleep apnea. Unfortunately, the patient did not tolerate CPAP during the titration study which resulted in very poor sleep efficiency. Subsequently, the patient was started on Auto PAP device with settings of 4-12 cm H2O. His mask was switched from full face mask to Amara View mask and he did tolerate that well.

Figure 2: Overnight pulse oximetry on APAP 4-12 cm H2O demonstrates normal SPO2 throughout the night.

In the follow up visit (six months later), the patient and his mother did notice significant improvement in excessive daytime sleepiness and more alertness and involvement with friends. There was resolution of snoring and apnea episodes. The download data from APAP device showed very good compliance (93% use => 4 hours with average use of 7 hours and 44 minutes, AHI 4.7,95th percentile leak was 19 L/M and 95th percentile pressure was 12 cmH2O). Overnight pulse oximetry conducted on APAP showed no evidence of nocturnal oxygen desaturation (Figure 2). The last CBC performed showed improvement in polycythemia and erythrocytosis (Hgb 18.4 g/dl, RBC 5.61 M/Ul, Hct 49.9%).


FXS is associated with multiple sleep problems. The prevalence of sleep disorders in patients with intellectual delay and autism spectrum disorder (ASD) ranges from 36% to 73% [2]. Insomnia of sleep initiation and maintenance is common. In one large parental survey of 1295 children with FXS, 32% reported insomnia [3]. There is an increased risk of sleep related breathing disorders (particularly obstructive sleep apnea). In one study, the prevalence of loud snoring and OSA was 38% and 34% respectively. The exact pathophysiology is not fully understood but it seems that the morphological facial features (e.g. long and narrow face, prominent forehead high arched palate, retrognathia and hypotonia) do play a role. In another study four out of seven patients with FXS were found to have obstructive sleep apnea with severe oxygen desaturation [4].

Although our patient presented with excessive daytime sleepiness, daytime fatigue, snoring and witnessed apnea, the major presenting reason was polycythemia and erythrocytosis. Improvement of polycythemia with PAP therapy supports the role of repetitive hypoxemia associated with severe obstructive sleep apnea in developing secondary polycythemia.

Most patients with FXS present with generalized anxiety, autistic features and behavioral problems that make the utilization of inlab polysomnography and the use of PAP therapy very challenging [5]. Although our patient had intellectual disability, fortunately anxiety was not prominent which enabled us to utilize overnight polysomnography to establish the diagnosis and use PAP therapy successfully. PAP therapy resulted in significant improvement in medical (polycythemia, nocturnal hypoxia) and psychiatric (anxiety, aggression) symptoms.

We encourage primary care providers and pediatricians to screen for sleep disordered breathing in patients with FXS.


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