Angelman Syndrome vs. Prader Willi Syndrome: Genetics and Clinical Features

Prader-Willi and Angelman syndromes are the two most common genetic disorders of imprinting. The concept of imprinting lies in the fact that the function of certain genes is dependent on their parents: maternal or paternal. Basically there is something wrong with the 15q11 region of the paternally derived chromosome in Prader Willi syndrome and that of the maternally derived chromosome in Angelman syndrome.

Prader-Willi phenotype can occur as a result of one of the following

1. Deletion of 15q11-q13 including the Prader-Willi critical region of the paternally derived chromosome 15 (most common)

2. Abnormality of the structure of Prader-Willi critical region of 15q11-q13 (for example translocation)

3. If the child has two maternally derived chromosome 15s. (Hence absence of paternal chromosome 15)

4. Mutations of imprinting control center genes (rare)

The critical region of chromosome 15 for Angelman syndrome is located very close to the Prader-Willi critical region. But, when deletion of the Angelman critical region results, it is the maternally derived chromosome that is affected.

Mechanisms leading to Angelman syndrome include the following:

1. Deletion of the 15q11-q13 including the Angelman critical region of the maternally derived chromosome 15 (most common)

2. Abnormality of the structure of the Angelman critical region of 15q11-q13 (e.g. translocation)

3. If the child has two paternally derived chromosome 15s. (Hence absence of maternal chromosome 15)

4. Mutations of imprinting control center genes (rare).

5. Mutations of the ubiquitin-protein ligase gene (UBE3A)

6. No identifiable etiologic mechanisms but a positive family history of other affected individuals and a classic phenotype

Clinical features of Prader Willi syndrome:


Newborns: hypotonia, poor sucking and swallowing, weak cry
Infancy: Delayed motor and speech development
Toddler: Hypotonia goes away! Extreme appetite leading to morbid obesity.

In addition hands and feet are noticeably small from birth, height is short and the penis and testes are hypoplastic. Patients have emotional lability and extreme temper tantrums.

Clinical features of Angelman syndrome:

Severe cognitive deficits; speech is heavily impared. Inappropriate paroxysms of laughter (happy puppets). Physical features include microcephaly, maxillary hypoplasia, large mouth, and short stature.Seizures are common. Except for case reports, all patients are infertile.