title: Delineation of late onset hypoventilation associated with hypothalamic dysfunction syndrome.
abstract: 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.
authors.affiliation: INSERM U781, Hôpital Necker-Enfants Malades, Paris, 75015, France. depontual@necker.fr
authors.forename: Loic
authors.initials: L
authors.lastname: De Pontual
authors.forename: Delphine
authors.initials: D
authors.lastname: Trochet
authors.forename: Sophie
authors.initials: S
authors.lastname: Caillat-Zucman
authors.forename: Othman A
authors.initials: OA
authors.lastname: Abou Shenab
authors.forename: Pierre
authors.initials: P
authors.lastname: Bougneres
authors.forename: Yanick
authors.initials: Y
authors.lastname: Crow
authors.forename: Steve
authors.initials: S
authors.lastname: Cunningham
authors.forename: Blandine
authors.initials: B
authors.lastname: Esteva
authors.forename: Lada Cindro
authors.initials: LC
authors.lastname: Heberle
authors.forename: Juliane
authors.initials: J
authors.lastname: Leger
authors.forename: Graziella
authors.initials: G
authors.lastname: Pinto
authors.forename: Michel
authors.initials: M
authors.lastname: Polak
authors.forename: Magdy Helmy
authors.initials: MH
authors.lastname: Shafik
authors.forename: Christian
authors.initials: C
authors.lastname: Straus
authors.forename: Ha
authors.initials: H
authors.lastname: Trang
authors.forename: Arnold
authors.initials: A
authors.lastname: Munnich
authors.forename: Stanislas
authors.initials: S
authors.lastname: Lyonnet
authors.forename: Isabelle
authors.initials: I
authors.lastname: Desguerre
authors.forename: Jeanne
authors.initials: J
authors.lastname: Amiel
mesh_terms: 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
chemical_list: 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