Referral Requirements
Important Note:
Diagnostic testing requires referral through Paediatrics, Neurology or Genetic Services.
Contacts:
Genetic Health Service NZ can be contacted on 0800 476 123.
Neurology can be contacted on (09) 307 4949 ext. 25662.
General Paediatrics can be contacted on (09) 307 4949 ext. 22559.
Background Information
Clinical features of Prader Willi syndrome (PWS) show a bi-phasic course. Neonates with PWS are hypotonic, are poor feeders and have a weak cry but improve over time. In later infancy, and childhood, the typical findings are global developmental delay, short stature, hypogonadism, small hands and feet, and marked hyperphagia leading to obesity.
Angelman syndrome (AS) is a non-progressive congenital disorder characterised by more significant developmental delay or mental retardation, ataxia, jerky arm movements, macrostomia, tongue thrusting, unprovoked laughter, virtual absence of speech and brachycephaly.
About 70 to 75% of patients with PWS and AS have a deletion at 15q11.2-q13, which may require high resolution chromosome analysis or FISH for visualisation at the chromosome level. In PWS, the deletion occurs on the paternal chromosome, whereas in AS, the deletion is on the maternal chromosome. An imbalance of functional maternal and paternal copies of this region of chromosome 15 also occurs due to uniparental disomy (UPD) or due to imprinting mutations. Approximately 25% of PWS patients show maternal UPD and approximately 5% of AS patients show paternal UPD. Imprinting mutations seem to be present in a small percentage of patients.
Within the PWS/AS critical region, the maternally and paternally derived chromosomes show specific methylation patterns, which reflect differences in imprinting of the two chromosomes. Methylation specific enzymes and a probe to this region can be used to analyse the methylation patterns present and therefore determine if both the maternal and paternal copies of the PWS/AS critical region are present.
