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Background Neuroimaging Gross Pathology Histopathology & Immunohistochemistry
BACKGROUND AND CLINICAL INFORMATION:
Head
Summary: Angelman syndrome is also known as the "Happy puppet syndrome". These patients are euphoric, frequently simile and with paroxysms of laughter. They also have unusual but characteristic posture characterized by flexion at the wrists and elbows when the arms are raised such that they resemble on a string. Clinically the patients have developmental delay and severe mental retardation, ataxia, seizure, hypotonia, postnatally developing microbrachyencephaly, and a characteristic facial appearance with macrostomia and prognathia. Abnormalities in the cerebrum have been revealed by Golgi impregnantation but very few cases have been studied histologically.
Physical
Features/Clinical:
Craniofacial:
Midface
hypoplasia, a large mouth, deep-set eyes and mandibular prognathism (a
promient chin). Macrostomia (large tongue) is present in childhood. Many
patients have a depression in the occipital bone near the posterior
fontanelle which is palpable as a horizontal groove with prominent occipital
condyle bilaterally.
Typical
posture of the upper limbs:
They have unusual but characteristic posture characterized by flexion at the
wrists and elbows when the arms are raised such that they resemble on a
string.
Visual
problem:
strabismus in about 40% of patients. Other anomalies include nystagmus and
refractive errors.
Others:
Otitis media is a frequent complication of the mid-face hypoplasia and poor
drainage of the eustachian tubes.
Behavior:
Severe
hyperactivity
in childhood which usually resolves by adulthood. Young children has a
tendency to constantly putting things in their mouths and constantly moving
from one object ot another.
Sleep
disturbance: In
about 90% of patients.
Intrusive
behavior:
biting, grabbing, and pinching.
Inpulsive
behavior and peculiar love of water:
The combination of the two often lead the patients to jump into a bath tub
or pool with their clothes on.
Fascination
for
things such as mirror or shinny objects.
Neurocognitive:
“Happy
puppet syndrome”: Patients
are happy. Frequent smiling and bouts of laughter begin between 16 months
and 3 years of age. The bouts of laughter may be provoked by minimal stimuli
or even painful stimuli.
Language
skill:
Severe developmental delay particularly in language skill and many patients
are completely non-verbal.
Seizures:
Usually develop between 18-24 months, seen in about 86% of patients. All
types of seizures can occur. Seizures subsequently disappear during or after
adolescence. Recurrance in adulthood may occur.
Neuroimaging:
Abnormalities
include: Cerebral
atrophy, cerebellar atrophy, partial agenesis of the temporal lobe, anomalous
gyral conbolutions.
Genetics:
Most
common is microdeletion of the long arm of chromosome 15q11-13 that is of
maternal origin (identifiable in approximately 60% of cases) which is the
same site as the chromosomal defect in Prader-Willi syndrome. The source of
the abnormal chromosome in Angelman syndrome is the mother (the paternal
gene is silenced by genetic imprinting), and in Prader-Willi syndrome, the
father (the maternal gene is silenced by genetic imprinting).
Uniparental
disomy: About 2% of them are due to paternal uniparental disomy (the child
has two copies of the father’s chromosome 15 but Is missing the mother’s
chromosome 15).
Imprinting
mutation: the patient shows an exclusively paternal methylation pattern on
the maternally derived alleles.
The
ubiquitin protein ligase E6-AP
of the proteasome pathway for protein degration is localized within
chromosome 15q11-13 and truncating mutatns of E6-AP is identified in
patients with Angelman's syndrome. [Kishino T et al., Nat. Genetics 1977
15:70; Sutcliffe JS et al., Genome Res 1997 7:368; Albrecht U et al., Nat,
Genetics 1997 17:75-78]
Abnormalities include: Cerebral
atrophy, cerebellar atrophy, partial agenesis of the temporal lobe, anomalous
gyral conbolutions.
No specific changes.
HISTOPATHOLOGY AND IMMUNOHISTOCHEMISTRY:
Head
No specific changes have been documented but the number of cases being studied are also limited. Abnormalities include minor perisylvian cerebral gyral abnormalities, partial agenesis of the corpus callosum, minor foci of neuronal dysplasia and heteropia in the temporal cortex and hypothalamus.
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Background Neuroimaging Gross Pathology Histopathology & Immunohistochemistry