Background: Prader-Willi Syndrome (PWS), due to loss of paternal gene expression on chromosome 15q11.2-13, is characterized by hypotonia, hypothalamic-pituitary dysregulation, abnormal respiratory drive, and hyperphagia. GH, often started in infancy, improves tone, body composition, and height. Concerns about sudden death in children with PWS started on GH, hypothesized secondary to worsening obstructive sleep apnea (OSA) from adenotonsillar hypertrophy, resulted in guidelines for polysomnography (PSG) evaluation before and after starting GH.
Method: We report two cases of worsened OSA in infants with PWS after GH due to unmasked laryngomalacia.
Results: Case 1 Female with PWS due to imprinting center epimutation. Initial PSG at 2 months old (mo) showed apnea hypopnea index (AHI) 15, obstructive AHI (oAHI) 12, nadir oxygen saturation (nO2) 94%. GH was started soon after (0.5 mg/m2 per day). PSG at 4 mo was significantly worse (AHI 31, oAHI 29, nO2 81%). GH was held and a flexible fiberoptic laryngoscopy (FFL) showed laryngomalacia. Supraglottoplasty was done at 5 mo. PSG at 6 mo showed improvement (AHI 6, oAHI 1.8, nO2 90%) so GH was restarted at 7 mo. Repeat PSG at 8 mo was stable (AHI 6, oAHI 4, nO2 88%).
Case 2 Female with PWS due to deletion. Initial PSG at 5 mo (AHI 15, oAHI 9, nO2 75%). GH was started at 7 mo (0.5 mg/m2 per day). PSG at 8 mo was significantly worse (AHI 33, oAHI 28, nO2 57%). GH was held and she had a adenotonsillectomy at 11 mo. Soon after, FFL showed laryngomalacia which was monitored and repeat PSG at 12 mo showed improvement (AHI 12, oAHI 8, nO2 71%). GH was resumed at 13 mo but repeat PSG at 16 mo was significantly worse (AHI 44, oAHI 30, nO2 61%) so GH was held again. PSG off GH at 22 mo was improved (AHI 13, oAHI 9, nO2 64%). Supraglottoplasty was done at 22 mo and PSG at 24 mo showed further improvement (AHI 8, oAHI 6, nO2 72%).
Conclusion: Respiratory difficulties can lead to significant morbidity in PWS. Laryngomalacia is not well described in this population but can exacerbate OSA. GH has significant benefit for infants with PWS but is monitored carefully due to concerns about aggravating OSA secondary to adenotonsillar hypertrophy. However, our cases demonstrate that GH may also unmask underlying laryngomalacia, possibly due to improved inspiratory force, which requires separate evaluation and treatment.
27 - 29 Sep 2018
European Society for Paediatric Endocrinology