Prader-Willi syndrome. Epidemiological, behavioural, language and neurochemical aspects

Abstract

Prader Willi syndrome (PWS) has not previously been the object of systematic controlled clinical, epidemiological or neurochemical studies in the Scandinavian countries. The aims of the present study, therefore, were to investigate: (1) the prevalence of PWS, (2) the behavioural phenotype of PWS, (3) the language and speech characteristics of the syndrome, and (4) certain neurochemical parameters in PWS. PWS prevalence in individuals under age 25 years was studied by screening the whole age-specific population in the county of Skaraborg, Sweden, suspected of suffering from or already diagnosed as having PWS. All kinds of special schools, careproviders and health staff were approached in the screening. Eleven individuals met the diagnostic criteria used in the late 1980s, yielding a prevalence of 1.2 in 10,000. The behavioural phenotype was studied at personal examination and psychiatric interviews with caregivers and, in cases with appropriate mental age, with the individuals suffering from PWS. Parents of a group of 44 individuals with PWS and of a comparison group were given interviews and questionnaires about their children's behaviour. Significantly raised levels of many types of behaviour problems were reported in individuals with PWS. Some behaviour features were characteristic of PWS when contrasted with same-sexed cases of similar age, body mass index (BMI) and IQ. Some of the characteristic behaviours emerge already in the first few years of life and most have become evident by age 7 years. Voice, speech and language skills were examined in 11 individuals with PWS, who were compared with 11 non-PWS cases matched for age, sex, IQ-level and BMI. Language skills were generally impaired in PWS. Oral motor function, pitch level and resonance were specifically disordered and clearly differentiated the PWS and comparison groups from each other. Certain perinatal risk factors separated PWS from other obese children and adolescents, but did not differentiate within the PWS group. Underlying cerebral dysfunction and a characteristic anatomy of the mouth and larynx were suggested to be important pathogenetic factors.The concentration of the metabolites of serotonin (5-HIAA), dopamine (HVA), and noradrenaline (HMPG) in the cerebrospinal fluid (CSF) were analyzed in 13 cases with PWS and compared with those of 56 individuals belonging to healthy and other contrast groups. Levels of 5-HIAA were markedly increased in the PWS group. Levels of HVA were also raised. The increased concentrations were found in PWS cases independently of age, BMI or IQ-level, suggesting that the monoamine disturbance might be linked with the core syndrome rather than with associated features. Platelet MAO-B activity in 17 PWS and 18 comparison cases was also analyzed. The activity was significantly higher in the PWS group, again suggesting monoamine dysfunction in this group.