TY - JOUR
T1 - Rapid-onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation presenting in childhood
AU - Ize-Ludlow, Diego
AU - Gray, Juliette A.
AU - Sperling, Mark A.
AU - Berry-Kravis, Elizabeth M.
AU - Milunsky, Jeff M.
AU - Farooqi, I. Sadaf
AU - Rand, Casey M.
AU - Weese-Mayer, Debra E.
PY - 2007/7
Y1 - 2007/7
N2 - OBJECTIVE. The goal was to characterize the phenotype and potential candidate genes responsible for the syndrome of late-onset central hypoventilation with hypothalamic dysfunction. METHODS. Individuals with late-onset central hypoventilation with hypothalamic dysfunction who were referred to Rush University Medical Center for clinical or genetic assessment in the past 3 years were identified, and medical charts were reviewed to determine shared characteristics of the affected subjects. Blood was collected for genetic testing of candidate genes (PHOX2B, TRKB, and BDNF) and for high-resolution conventional G-banding, subtelomeric fluorescent in situ hybridization, and comparative genomic hybridization analysis. A subset of these children were studied in the Pediatric Respiratory Physiology Laboratory at Rush University Medical Center. RESULTS. Twenty-three children with what we are now naming rapid-onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation were identified. Comprehensive medical charts and blood for genetic testing were available for 15 children; respiratory physiology studies were performed at Rush University Medical Center on 9 children. The most characteristic manifestations were the presentation of rapid-onset obesity in the first 10 years of life (median age at onset: 3 years), followed by hypothalamic dysfunction and then onset of symptoms of autonomic dysregulation (median age at onset: 3.6 years) with later onset of alveolar hypoventilation (median age at onset: 6.2 years). Testing of candidate genes (PHOX2B, TRKB, and BDNF) revealed no mutations or rare variants. High-resolution chromosome analysis, comparative genomic hybridization, and subtelomeric fluorescent in situ hybridization results were negative for the 2 patients selected for those analyses. CONCLUSIONS. We provide a comprehensive description of the clinical spectrum of rapid-onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation in terms of timing and scope of symptoms, study of candidate genes, and screening for chromosomal deletions and duplications. Negative PHOX2B sequencing results demonstrate that this entity is distinct from congenital central hypoventilation syndrome.
AB - OBJECTIVE. The goal was to characterize the phenotype and potential candidate genes responsible for the syndrome of late-onset central hypoventilation with hypothalamic dysfunction. METHODS. Individuals with late-onset central hypoventilation with hypothalamic dysfunction who were referred to Rush University Medical Center for clinical or genetic assessment in the past 3 years were identified, and medical charts were reviewed to determine shared characteristics of the affected subjects. Blood was collected for genetic testing of candidate genes (PHOX2B, TRKB, and BDNF) and for high-resolution conventional G-banding, subtelomeric fluorescent in situ hybridization, and comparative genomic hybridization analysis. A subset of these children were studied in the Pediatric Respiratory Physiology Laboratory at Rush University Medical Center. RESULTS. Twenty-three children with what we are now naming rapid-onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation were identified. Comprehensive medical charts and blood for genetic testing were available for 15 children; respiratory physiology studies were performed at Rush University Medical Center on 9 children. The most characteristic manifestations were the presentation of rapid-onset obesity in the first 10 years of life (median age at onset: 3 years), followed by hypothalamic dysfunction and then onset of symptoms of autonomic dysregulation (median age at onset: 3.6 years) with later onset of alveolar hypoventilation (median age at onset: 6.2 years). Testing of candidate genes (PHOX2B, TRKB, and BDNF) revealed no mutations or rare variants. High-resolution chromosome analysis, comparative genomic hybridization, and subtelomeric fluorescent in situ hybridization results were negative for the 2 patients selected for those analyses. CONCLUSIONS. We provide a comprehensive description of the clinical spectrum of rapid-onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation in terms of timing and scope of symptoms, study of candidate genes, and screening for chromosomal deletions and duplications. Negative PHOX2B sequencing results demonstrate that this entity is distinct from congenital central hypoventilation syndrome.
KW - Alveolar hypoventilation
KW - Autonomic nervous system dysregulation
KW - BDNF gene
KW - Hypothalamic dysfunction
KW - NTRK2 gene
KW - PHOX2B gene
KW - Rapid-onset obesity
UR - http://www.scopus.com/inward/record.url?scp=34447118767&partnerID=8YFLogxK
U2 - 10.1542/peds.2006-3324
DO - 10.1542/peds.2006-3324
M3 - Article
C2 - 17606542
AN - SCOPUS:34447118767
SN - 0031-4005
VL - 120
SP - e179-e188
JO - Pediatrics
JF - Pediatrics
IS - 1
ER -