Angelman Syndrome

 

Epidemiology and Etiology:

    • del(15)(q11q13)mat (70%)
    • upd(15)pat (3-5%)
    • UBE3A (E6-AP) mutations (5%)
      • Ubiquitin-protein ligase E3A
    • Abnormal imprinting by methylation analysis (3%)
    • Idiopathic (10-14%)
    • de novo (great majority)

 

Common sites:

    •  

 

Gross features:

    • Distinctive facies
    • spasticity

 

Histologic features:

    •  

 

Immunophenotype:

Marker:

Sensitivity:

Specificity:

 

 

 

 

Molecular features:

    • SNRPN methylation abnormality (80%)
      • Only unmethylated alleles
    • 4 Mb deletion (15q11-q13)
      • 2 proximal sites (BP1 for type 1, BP2 for type 2)
      • 1 distal site (BP3)
      • Those with larger class I deletions:
        • More likely to meet autistic criteria
        • Lower cognitive scores
        • Lower expressive language scores
        • More medications to control seizures
      • 4 genes that are deleted in class I but not class II deletions:
        • NIPA1
        • NIPA2
        • CYFIP1
        • GCP5
    • UBE3A mutations

 

Other features:

    • severe mental retardation
    • absent speech
    • ataxic movements and gait
    • increased tone after infancy
    • seizures
    • happy disposition with paroxysmal laughter

 

References:

    • ACMG statement on diagnostic testing for UPD (2001)
    • Thompson & Thompson 2008