The 11p15 ICR1 epimutation is a major, specific cause of RSS exhibiting failure to thrive. We propose a clinical scoring system (including a BMI < -2 SDS), highly predictive of 11p15 ICR1 LOM, for the diagnosis of RSS.

Severe Cushing's syndrome developed in a man of 35 years. Plasma ACTH and lipotrophin hormone levels were supranormal, and dexamethasone failed to stop their production. An ACTH-producing thymic carcinoid tumour was found to be responsible for the Cushing's syndrome. The tumour tissue contained pro-opiomelanocortin (POMC)-mRNA and POMC-related peptides. In addition, human corticotrophin-releasing hormone (h-CRH) (0.25 ng/mg wet tissue) was identified in the tumour extract. Among a series of extracts from two normal and three tumoral (Nelson's syndrome) pituitary glands, six non-pituitary POMC-producing tumours and five normal thymuses examined, only the extract from the thymic tumour of our patient contained h-CRH. The molecule isolated had the same properties as synthetic h-CRH (dilution, Sephadex G 50 chromatography). Circulating h-CRH levels, however, were normal. The possible involvement of such ectopic CRH production in the aetiology of Cushing's syndrome remains uncertain.