Describe the genomic Imprinting of Prader-Willi & Angelman Syndromes.

Definition

Prader-Willi and Angelman syndromes both involve the 15q11–q13 region and classically illustrate genomic imprinting — the phenotype depends on the parent of origin of the missing/abnormal genetic material.

Prader-willi Syndrome (loss of Paternal 15Q11–13)

• Neonatal hypotonia and poor feeding, then hyperphagia and obesity in childhood.
• Short stature, hypogonadism, small hands/feet, almond-shaped eyes, and intellectual disability/behavioural problems.

Angelman Syndrome (loss of Maternal 15Q11–13)

• 'Happy puppet' — ataxic, jerky movements, inappropriate laughter.
• Severe intellectual disability, absent speech, seizures.

Diagnosis

Confirmed by molecular tests (methylation studies, fish/microarray) of the 15q11–13 region — the same region, different parent of origin, gives two very different syndromes.

Mechanisms

The syndromes arise from deletion, uniparental disomy or imprinting defects of 15q11–13; because certain genes are expressed only from one parental copy, loss of the paternal copy causes Prader-Willi and loss of the maternal copy causes Angelman.

Management

• Prader-Willi — strict dietary/environmental control of hyperphagia, growth hormone, hormone replacement, and behavioural support.
• Angelman — seizure control, communication aids, physiotherapy and family support.

Diagnostic Approach

Methylation-specific testing of 15q11–13 detects most cases of both syndromes; further tests (fish, microarray, uniparental disomy studies) define the exact mechanism, which affects recurrence risk.

Prognosis & Follow-up

Both are lifelong conditions requiring multidisciplinary follow-up; Prader-Willi care centres on preventing obesity-related complications, and Angelman care on seizures, communication and mobility.

Same locus, opposite parent of origin — the classic imprinting example.