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Background Neuroimaging Gross Pathology Histopathology & Immunohistochemistry Reference
BACKGROUND AND CLINICAL INFORMATION:
Head
Summary: Most
of the clinical features of Prader-Willi syndrome are believed to be a result of
hypothalamic insufficiency. This syndrome is characterized by severe infantile
hypotonia, subsequent hyperphagia (overeating with a lack of satiation) and
rapid weight gain after the first year, morbid obesity, obsessive compulsive
behavior, mild to moderated developmental delay, and hypogonadism.
Neuropathologic changes are usually limited to the paraventricular nuclei.
Incidence: 1
in 15,000 in the general population.
Genetics: Microdeletion
of the long arm of chromosome 15q11-13 that is of paternal origin. The maternal
gene is silenced by genetic imprinting.
Physical Features/Clinical:
Fetus: Reduced fetal activity and breech delivery is
common.
Infantile
hypotonia: Marked infantile hypotonia with feeding difficulty
that necessitate tube feeding. Respiratory difficult is not a common
picture. Crying is high-pitched and often weak. The hypotonia improves with
age and the child will eventually be able to walk.
Developmental delay: There is delay of developmental milestones.
Severe hypotonia leading to poor suck and failure to thrive. They have
an unusual and weak cry described as kitten-like or squeaky.
Deep tendon reflexes are weak.
Endocrine features and genital
hypoplasia: They are
secondary to hypothalamic insufficiency and infertility is the rule in both
sexes. In male, unilateral or bilateral cryotochorchidism is present in 80%
of patients; scrotal hypoplasia or micropenis are recognizable during the
newborn period. Hypogonadism is less obvious in female newborns. Menache is
usually delayed and oligomenorrhea is common; menache may not occur at all.
Breast size is usually small; clitoris and labia are hypoplastic.
Obesity: This is the most severe problem. The weight is
below normal initially because of hypotonia. Food intake improves and
eventually hyperphagia develops between 2 and 6 years of age with a lack of
normal satiation; severe obesity is often the result. The patients have an
obsession for food and are unable to vomit, two factors that aggrevate the
obesity. Complications of obesity including somnolence and hypoventilation
sometimes leading to Pickwickian syndrome, hypertension, type-II diabetes
mellitus, corpulmonale and right heart failure.
Craniofacial features: Typical facial features include a narrow bifrontal
diameter and the skull is often dolicocephalic; some patients may be
macrocephalic. A small mouth
with a thin and downturned upper lip that gives the mouth a triangular shape
(fish-mouth shaped mouth), a feature probably resulted from the hypotonia
and poor prenatal neuromuscular functioning. Oral co-ordination problems are
common. The saliva is sticky and viscous. Dental problems include delayed
eruption of teeth, dental caries, malocclusion, and enamel hypoplasia.
Almond-shaped eyes with a slight upslant laterally. Ophthalmic abnormalities
include strabismus and myopia. Hypopigmentaion is seen in about half of the
patients.
Hypopigmentation is more often seen in aptients with a deletion. The
hypopigmentation in the eye and elsewhere is thought to be associated with
hemizygosity of the P gene that is
located within the 15q11-13 region. This gene encodes a protein that
transports tyrosine across the membrane. About 1% of these patients with
Prader-Willi syndrome or Angelman syndrome have type II oculocutaneous
albinism which is secondary to an inherited pathological mutation in the P
gene on the normal chromosome 15 in addition to the deletion. Misrouting
of the optic fibers in the central pathway has been demonstrated in
these patients.
Undesented testis in male.
Neurocognitive:
IQ: The
range is from average to profoundly retarded.
Strength: Long-term
memory, particularly for incidental information. Visual-spatial percepual
abilities and visual memory. Reading decoding, acquied information and
vocabulary.
MRI is usually within normal limits.
No reproducible macroscopic changes.
HISTOPATHOLOGY AND IMMUNOHISTOCHEMISTRY:
Head
Paraventricular
nucleus: Pathologic changes are usually limited only to the paraventricular
nuclei. Hayashi
M et al., Brain Dev 1992 Jan;14(1):58-62
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Background Neuroimaging Gross Pathology Histopathology & Immunohistochemistry Reference