ESPE Abstracts (2019) 92 P3-192

Rohhad Syndrome: Report of 2 Rare Cases From Crete-Greece

Pinelopi Smyrnaki1,2, Maria Chrysoulaki2, Vasiliki Daraki2, Grigoria Betsi2, Maria Sfakiotaki2, Paraskevi Floroskoufi2, Katerina Bouki2, Diamandis Kofteridis2, Christina Kanaka-Gantenbein1, Paraskevi Xekouki2


11 Division of Endocrinology, Diabetes and Metabolism, First Department of Pediatrics, Medical School, National and Kapodistrian University of Athens, "Agia Sofia" Children's Hospital, Athens, Greece. 2Endocrinology, Diabetes and Metabolism Clinic, University General Hospital of Heraklion, Heraklion, Greece


Introduction: ROHHAD syndrome (Rapid-onset Obesity with Hypoventilation, hypothalamic and autonomic dysregulation) is a rare and complex disease with potential fatal outcome. To this day there have been 158 cases reported in the literature while whole exome sequencing has not yet revealed any responsible genes. It usually presents at the age of 2-4 years and the diagnosis is based on the following criteria: 1) rapidly progressive obesity that develops at the age of 2-7 years 2) hypothalamic dysfunction 3) alveolar hypoventilation 4) dysregulation of the autonomic nervous system. In about 40% of the patients, neuroendocrine tumors have also been reported (ROHHAD-NET).

Aim: We hereby present, for the first time in Greece, two rare cases of ROHHAD syndrome from Crete.

Case Presentation: The first case, 20-year-old female, initially presented to the pediatric endocrinology outpatient care at the age of 9.5 with precocious puberty and obesity since the age of 4 years. On physical examination,her BMI was 27.6 kg/m², (>97th percentile), her height 1.46m and her bone age 12 years according to Greulich and Pyle. Pituitary MRI revealed a Rathke cyst without any other abnormal findings while laboratory testing showed hyperprolactinemia and low IGF-1. During follow up, the patient developed secondary amenorrhea, hypernatremia attributed to disrupted thirst mechanism, severe thermal dysregulation, hypothyroidism, while further testing with sleep study revealed obstructive sleep apnea, strongly suggesting ROHHAD syndrome. The second patient is a 16.5 year old boy who presented for the first time to the endocrinology outpatient care at the age of 14 years with significant obesity (BMI 38,08 >97th percentile) and metabolic syndrome. His height was 152cm (10th percentile) and his weight 88kg (>97th percentile) while he also demonstrated delayed puberty (Tanner 2, testicular volume 6ml), acanthosis nigricans and multiple vertical reddish-purple skin striae. His bone age was compatible with his chronological age. Laboratory testing revealed hypernatremia, hyperprolactinemia, hypogonadotrophic hypogonadism, growth hormone deficiency with normal cortisol secretion, insulin resistance, fatty liver disease, while sleep study demonstrated sleep apnea syndrome of increased severity for his age; findings compatible with ROHHAD syndrome. Currently, both patients receive hormonal replacement therapy while they also use a non invasive ventilation device (C-PAP).

Conclusion: ROHHAD syndrome is a rare disease which presents early in childhood. Rapidly progressive obesity and hypothalamic dysfunction are usually the first detectable signs of the disease. Prompt recognition of the syndrome as well as treatment of hormonal dysfunction and alveolar hypoventilation may prevent severe complications and increased morbidity mainly due to cardiopulmonary arrest.