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Diagnosis of Prader-Willi syndrome

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The relationship between genotype and phenotype in Prader-Willi syndrome has not been completely delineated. Clinical diagnosis is based on a list of major or minor criteria present in the neonatal period and in later childhood, adolescence, and adult life. Genetic diagnosis is dependent on methylation analysis at the SNURF/SNRPN locus. A study based on the former Anglia and Oxford Health Region (J Whittington and colleagues. (

) has provided more data about the relationship between clinical features and genetic diagnosis.

The study included 103 people with positive genetic tests for Prader-Willi syndrome. Sixty-one of these were from a population based sample within the region and 42 from other regions). There were 19 with negative genetic tests but positive clinical criteria, and 10 from the population study with neither appropriate clinical criteria nor positive genetic tests plus 22 controls with learning disorders of other aetiologies.

Four neonatal criteria were invariably present when genetic testing was positive; they were poor suck, feeding problems, floppiness at birth, and weak cry or inactivity. Hypogonadism was also an invariable accompaniment of the genetic diagnosis. When all learning-disabled subjects were considered the combination of poor suck at birth, weak cry or inactivity in infancy, decreased vomiting, and thick saliva correctly distinguished between Prader-Willi syndrome and other diagnoses in 92% of cases. No combination of clinical features, however, predicted a positive genetic diagnosis with certainty. When there is no information about neonatal features the most discriminatory clinical features are hypogonadism, small hands and feet, thick saliva, more than usual stubbornness, and insensitivity to hot and cold.

The authors of this paper suggest use of the core neonatal criteria to decide about genetic testing in infancy. In later life, if neonatal data are unavailable, indications for genetic testing include eating disturbance and learning disabilities together with hypogonadism (including infrequent (<5 per year) and sparse menstruation in postpubertal girls or women).

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