UNEXPECTED DEATH AND CRITICAL ILLNESS IN PRADER-WILLI SYNDROME:  REPORT OF NINE INDIVIDUALS 

DA Stevenson, MD^1,6, TM Anaya¹, MD, J Clayton-Smith, MD², B Hall, MD³, MI Van Allen, MD⁴, RT Zori, MD⁵, CL Clericuzio, MD¹

 ¹Univ. of New Mexico, Albuquerque, NM;  ²St. Mary’s Hospital, Manchester, UK;  ³Univ. of Kentucky, Lexington, KY;  ⁴Univ. of BC, Vancouver, BC, Canada;  ⁵Univ. of Florida, Gainesville, FL;  ⁶Univ. of Utah, Salt Lake City, UT  

Individuals with Prader-Willi syndrome (PWS) generally survive into adulthood.  Common causes of death are cor pulmonale and respiratory failure.  In 1996, Clericuzio et al. reported three children who died suddenly in the first two years of life and two others with life threatening illnesses. Schrander-Stumpel et al. in 1998 reported the deaths of an additional three children. Since 1996, we have learned of an additional four individuals with PWS who have died unexpectedly and report here on a total cohort of seven children and two adults with unexpected death or critical illness.

Deaths:  Infants :  Case 1, a 5-month-old male, died after admission for fever. Autopsy found no cause of death. Case 2, a 9-month-old male, died after 24 hours of diarrhea with subjective fever. Autopsy found no cause of death. Case 3, a 19 month-old female was found dead after a febrile respiratory tract infection. There was no autopsy. Toddlers: Case 4, a 3.5 year old male, was found dead in the morning after being well the night before. Death was thought to be secondary to apnea. Case 5, a 3.5 year old female, died in the hospital, comatose after admission for vomiting and diarrhea. Autopsy showed viral gastroenteritis, adrenal hypoplasia, but cause of death was not found. Adults: Case 6 was a 29-year-old severely retarded male who collapsed suddenly after vomiting twice. Autopsy showed acute and chronic aspiration, but no definite cause of death. Case 7 was a 43-year-old group home client who died while taking an unsupervised tub bath.  She had lost 215 pounds several years earlier. No autopsy was done, but it was hypothesized that she fell asleep and drowned. Critical Illness:  Case 8, a female, had two admissions in infancy with fever near 43 C with shock, one with pneumonia, one with diarrhea. Case 9, a female, developed severe dilated cardiomyopathy at age 17 months.  

These data show age-specific characteristics of PWS patients with fatal or life-threatening illnesses. Under age 2, childhood illnesses were associated with extremely high fevers and rapid demise or near-demise. Hypothalamic dysfunction likely plays a role in exaggerated fever response, but also perhaps in central regulation of adrenal function. Hypoplastic adrenal glands were found in one child, which raises again the possibility of unrecognized adrenal insufficiency in individuals with PWS and emphasizes the vital role of autopsy. The adult tub drowning could be related to central hypersomnia, which has been reported in PWS. Tub drowning is essentially unheard of in the forensic drowning literature in the absence of intoxication, seizure or arrhythmia. Lastly, we have a subjective impression that those individuals with extreme medical vulnerability have in general a more severe developmental phenotype than average. This impression bears further investigation, as it may provide a guideline for identifying individuals with PWS who require particularly close medical monitoring.

July 2002