Novel autonomic dysregulation score in children with hypothalamic syndrome.

Objective: Rapid-onset obesity with hypothalamic dysfunction, hypoventilation and autonomic dysregulation (ROHHAD) is a rare syndrome manifesting in childhood. Diagnosis of ROHHAD syndrome remains challenging due to the diversity of symptoms that may be missed easily, especially for autonomic dysfunction, and partly develop later in time. The 2023 hypothalamic syndrome (HS) diagnostic criteria are a novel tool for recognizing symptoms of hypothalamic dysfunction. However, symptoms of autonomic dysregulation are lacking in these criteria. They are therefore insufficient for use in ROHHAD patients. No other scoring system for autonomic dysfunction in ROHHAD syndrome exists. We aim to improve the diagnostic criteria for HS by including a score for autonomic dysregulation, supporting early diagnosis of ROHHAD syndrome. Methods: A score for autonomic dysregulation in ROHHAD syndrome supplementary to the 2023 HS diagnostic criteria was developed based on existing instruments to assess autonomic dysfunction symptoms adjusted for specific symptoms in ROHHAD syndrome, with a score ranging from 0 to 10. The diagnostic criteria for HS including our add-on were tested retrospectively in four ROHHAD patients. Results: Four ROHHAD patients, median age 9.4 years (range 4.6-25.7), were assessed regarding signs and symptoms of HS and autonomic dysfunction. All patients had HS and scored on at least three different domains of autonomic dysregulation. Median score was 9 out of 10 (range 4-9). Conclusions: The 2023 HS diagnostic criteria are not sufficient to recognize autonomic dysfunction due to hypothalamic dysfunction in ROHHAD syndrome. Our add-on score is clinically easy to use and may help in early recognition and follow-up in ROHHAD syndrome and other causes of HS. Significance statement: Rapid-onset obesity with hypothalamic dysfunction, hypoventilation and autonomic dysregulation (ROHHAD) is a rare cause of HS in childhood. In the recently developed diagnostic criteria for HS, the autonomic manifestations of hypothalamic dysfunction, which are common in ROHHAD syndrome, are not represented sufficiently. Children with ROHHAD may, for example, experience ophthalmological problems (strabismus or oculomotor apraxia), altered pain threshold, increased or impaired sweating, cold extremities, and/or heart rate dysregulation. Many of these symptoms are mostly unnoticed by the clinician or caregivers, leading to a delay in diagnosis and treatment. An add-on to the diagnostic criteria for HS including parameters of autonomic dysregulation will support early recognition of ROHHAD syndrome, follow-up during treatment and research purposes.