Delineation of late onset hypoventilation associated with hypothalamic dysfunction syndrome.
Late Onset Central Hypoventilation Syndrome associated with Hypothalamic Dysfunction (LO-CHS/HD) is a distinct entity among the clinical and genetic heterogeneous group of patients with late onset central hypoventilation. Here we report a series of 13 patients with LO-CHS/HD. Rapid onset obesity is the first symptom of HD followed by hypoventilation with a mean delay of 18 mos. The outcome remains poor for this group of patients and would benefit from early diagnosis to anticipate ventilation and possible metabolic disorders. Tumor predisposition is more frequent than initially suspected and as high as 40% in this series. These tumors of the sympathetic nervous system (TSNS) are usually differentiated and do not significantly worsen the prognosis. We report a familial case with recurrence in siblings. The cause underlying LO-CHS/HD remains poorly understood although recurrence in siblings argues for a monogenic disorder. We ruled out PHOX2B, ASCL1, and NECDIN as disease-causing genes by direct sequencing in our series of patients and discuss possible disease-causing mechanisms.
De Pontual
Loic
L
INSERM U781, Hôpital Necker-Enfants Malades, Paris, 75015, France. depontual@necker.fr
Trochet
Delphine
D
Caillat-Zucman
Sophie
S
Abou Shenab
Othman A
OA
Bougneres
Pierre
P
Crow
Yanick
Y
Cunningham
Steve
S
Esteva
Blandine
B
Heberle
Lada Cindro
LC
Leger
Juliane
J
Pinto
Graziella
G
Polak
Michel
M
Shafik
Magdy Helmy
MH
Straus
Christian
C
Trang
Ha
H
Munnich
Arnold
A
Lyonnet
Stanislas
S
Desguerre
Isabelle
I
Amiel
Jeanne
J
D017668:Age of Onset; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D005260:Female; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D007027:Hypothalamic Diseases / Q000150:complications* / Q000235:genetics* / Q000503:physiopathology; D007040:Hypoventilation / Q000209:etiology* / Q000235:genetics* / Q000503:physiopathology; D007223:Infant; D008297:Male; D009419:Nerve Tissue Proteins / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics
D051792:Basic Helix-Loop-Helix Proteins; D018398:Homeodomain Proteins; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D014157:Transcription Factors; C065500:ASCL1 protein, human; C109220:NBPhox protein; C069766:necdin