A survey on Prader-Willi syndrome in the Italian population: prevalence of historical and clinical signs.

Prader-Willi syndrome (PWS) is characterized by hypotonia and feeding problems in neonatal period, hyperphagia and rapid weight gain after the first year of life, mental retardation, behavioral problems and hypogenitalism. For diagnosis, anamnestic and clinical criteria have been established by consensus in 1993 (Holm and Cassidy). Then, definitive genetic analysis became available. Subsequently revised criteria according to age have been proposed in 2001 in order to raise diagnostic suspicion to prompt genetic tests, avoiding expense of testing unnecessarily.The aim of our study was to analyse the frequency of anamnestic and clinical features in Italian PWS population in order to assess their validity in raising diagnostic suspicion and in identifying the patients to test genetically. We evaluated 147 patients with PWS (67 m, 80 f), aged 0.9-34.6 yrs (13.6 ± 6 yrs) with genetically confirmed diagnosis of PWS using the consensus diagnostic criteria. Data where classified according to age, sex and genotype. All PWS patients achieved the score according to the clinical diagnostic criteria.The frequency of features changed with age and sex. Sensitivities of some major clinical signs as neonatal hypotonia and learning problems (in patients > 6 yrs old) ranged from 96 to 100% in both sex. Cryptorchidism was present in 100% of cases, while female genital hypoplasia ranged from 50 to 75% without any significant difference between ages. Feeding problems in infancy varied from 25 to 82% in females and from 80 to 88% in males, meanwhile characteristic facial features varied from 67 to 100% in females and from 50 to 100% in males without any significant difference between ages. The sensitivity of hyperphagia and excessive weight gain increased with age, in both sex, reaching 100% after 13 years. The sensitivity of some minor and supportive criteria like characteristic behaviour problems, myopia, saliva alteration, skin picking, scoliosis and/or kyphosis, early adrenarche changed significantly with age. Speech defects and osteoporosis changed with age only in females. It is noticeable that some clinical signs as acromicria and behavioural problems, scoliosis and/or kyphosis, considered as minor or supportive by Holm and Cassidy, emerged to have higher sensitivity than some major criteria, and, therefore, more useful to support the diagnosis of the syndrome. Hypopigmentation and acromicria were significantly more frequent in subjects with deletion than those with UPD, meanwhile osteoporosis was more frequent in patients with UPD. This study demonstrates that some clinical characteristics are particularly frequent during specific ages of life and therefore confirms the necessity of a classification of criteria according to age as already suggested previously.