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A 5 year old girl with Prader-Willi syndrome and worsening snoring during growth hormone therapy

Case Editor - Kamyar Afshar

Reviewed By Clinical Problems Assembly

Submitted by

Camilla K. B. Matthews, MD

Assistant Professor

Department of Pediatrics

Wisconsin Sleep Center, University of Wisconsin School of Medicine and Public Health

Madison, Wisconsin

Mihaela Teodorescu, MD, MS

Assistant Professor

Department of Medicine

Wisconsin Sleep Center, University of Wisconsin School of Medicine and Public Health

Madison, Wisconsin

Submit your comments to the author(s).

History

A 5 year-old girl with Prader-Willi syndrome (PWS) on growth hormone (GH) therapy since 14 months of age was seen in evaluation for obstructive sleep apnea (OSA), due to increased snoring and possible breathing pauses during sleep. The patient was born in Korea and had been diagnosed with PWS by genetic analysis as an infant.  GH was started at age 14 months. No sleep study was performed at that time. After almost 3 years on treatment, her mother noted that the patient was snoring with increased frequency and severity, with possible breathing pauses during sleep. Over the past 6 months, her weight had also increased due to the consumption of large portion sizes of food and increased inactivity related to recent surgical procedures for bilateral hip dysplasia. She had no prior history of adenoidectomy or tonsillectomy.

Physical Exam

On exam, the patient had a blood pressure of 102/84 mm Hg and pulse of 111 beats/min. Her BMI was 28 kg/m2, compared to 20 kg/m2 one year previously. Her general appearance was notable for obesity and the general facies of a child with PWS, including almond-shaped eyes, thin upper lip, and down turned corners of the mouth.  HEENT exam showed no thyromegaly, however, her tonsils were 4+. Her lungs were clear to auscultation. The cardiac exam showed a regular heart rate without murmur or gallop. Musculoskeletal exam revealed subtle scoliosis. Her gait was broad based.  The skin exam revealed well healed scars on the hips from osteotomies for bilateral hip dysplasia.  The neurological exam was notable for diffuse hypotonia.  Her skin exam was normal.

Lab

Although no baseline IGF-1 data was available for the patient, her IGF-1 level had risen during GH therapy from 340 ng/ml (laboratory's normal range 66-351 ng/ml) at 28 months into treatment, to 514 ng/ml a few months prior to her sleep evaluation.

The patient was referred for a nocturnal polysomnogram (PSG). As depicted below (Fig 1), she was found to have severe OSA with an apnea-hypopnea index (AHI) of 24 events/hour and a REM sleep AHI of 38 events/hour and a lowest oxygen saturation of 81% (Fig 2).

Figures

LEOG AND REOG, left and respectively right outer cantus electro-oculography electrodes; F3-M2, C3-M2 and O1-M2, left frontal, central and respectively, occipital electroencephalography electrodes; F4-M1, C4-M1 and O2-M1, right frontal, central and respectively, occipital electroencephalography electrodes; Chin EMG, submental electromyography signal; INT EMG, intercostals electromyography signal; ECG II, one standard electrocardiogram lead; RTibial and LTibial, right and respectively left lower limbs electromyography electrodes; SNORE, the snoring sound via microphone; TFLOW, the airflow via nasal/oral thermocouples; PFLOW, the airflow via nasal air pressure transducer; CHEST and ABDO, chest and respectively abdominal walls motion via inductive plethysmography; SpO2, the pulse oximetry by finger probe; PLETH, phlethysmographic waveform; POSITION, S=Supine; PCO2 and ETCO2, end tidal CO2 monitoring with accompanying waveform.

 


Hypnogram from baseline PSG depicting multiple respiratory events, more frequent and with lower oxygen desaturations during supine-REM sleep

Figure 2: Hypopneas recorded more frequently during supine-REM sleep

Figure 3: Hypnogram from follow-up PSG showing significant improvement in sleep-disordered breathing.

Figure 4: Follow-up PSG showing hypopnea and variability in airflow (see arrows) during supine REM sleep.

Figure 5: Follow-up PSG continued to show variability in the plethysmographic waveform (see arrows) during NREM sleep suggesting increased upper airway resistance.

Question 1

What would be your recommendation to assess her snoring and witnessed apneas?

References

  1. Nixon GM, Brouillette RT. Sleep and Breathing in Prader-Willi Syndrome. Pediatric Pulmonology 2002; 34:209-217.
  2. Camfferman D, McEvoy RB, O’Donoghue F, Lushington K. Prader Willi syndrome and excessive daytime sleepiness. Sleep Medicine Reviews 2008; 12:65-75.
  3. Camfferman D, Lushington K, O’Donoghue F, McEvoy RB. Obstructive sleep apnea syndrome in Prader-Willi Syndrome: an unrecognized and untreated cause of cognitive and behavioral deficits? Neuropsychol Rev 2006; 16:123-129.
  4. Pavone M, Paglietti MG, Petrone A, Crino A, De Vincentiis GC, Cutrera R. Adenotonsillectomy for obstructive sleep apnea in children with Prader-Willi Syndrome. Pediatric Pulmonology 2006; 41:74-79.
  5. Grugni G, Livieri C, Corrias A, Sartorio A, Crino A. Death during GH therapy in children with Prader-Willi syndrome: description of two new cases. J Endocrinol Invest 2005; 26(6):554-557.
  6. Miller JL, Shuster J, Theriaque D, Driscoll DJ, Wagner M. Sleep disordered breathing in infants with Prader-Willi syndrome during the first 6 weeks of growth hormone therapy: a pilot study. J Clin Sleep Med. 2009; 5(5):448-453.
  7. Miller J, Silverstein J, Shuster J, Driscoll D, Wagner M. Short-term effects of growth hormone on sleep abnormalities in Prader-Willi syndrome. J Clin Endocrinol Metab 2006; 91:413-417.
  8. Eiholzer U. Deaths in Children with Prader-Willi Syndrome. Horm Res 2005; 63:33-39.