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Patient Y.D.
Clinicopathologic Conference (CPC)
Neurology Resident: Natalia Gonzalez
Pathologist: Ronald Hamilton
HPI: Y.D. was a male infant born at 37 weeks via elective C-section. A second
trimester prenatal ultrasound was concerning for ventriculomegaly, a dilated left
renal pelvis with hydroureter, a small VSD, and a two vessel cord.
At delivery, the infant was limp with poor respiratory effort requiring intubation. A
VPS shunt was placed. The infant passed at 2 weeks of age from
cardiorespiratory failure after life support was withdrawn.
FH: Mother was 33yo, G3P2. Family is from Mexico. Patient has a healthy 17 yo
brother and 8 yo sister.
Physical Examination
Vitals: Birth weight was 6.6 lbs. OFC 41cm (97 %ile).
HEENT: Macrocephaly. Large anterior and posterior fontanelles. Microphthalmia.
Low set and posteriorly rotated ears. Right iris coloboma. Slit lamp: anomolous iris
b/l with multiple vessels and persistent pupillary membranes. Dense cataracts.
Anterior and posterior fetal vasculature.
Derm: Tuft of hair over sacral region (ultrasound normal underneath)
Ext: Single palmar creases. Digitalized right thumb. Bilateral 5th clinodactyly.
Neuro: Responds to stimulus with flexion of ext. Otherwise no movements. Pupils
unreactive bilaterally. + oculovestibular response. Decreased axial tone. Normal
tone in extremities. DTRs elicited in patella bilaterally. Babinski and plantar grasp
Fetal ventriculomegaly (ventricle width > 10mm)
1. Obstructive
1. Dysgenesis
1. Destructive
Ventricles are typically smooth-walled.
Ventricle orientation is normal.
Cortex is intact, but compressed.
Posterior fossa structures may be abnormal. If normal, consider
aqueductal stenosis.
Cavum septum pellucidum may be absent if severe.
The falx is present.
Ventricle shape and position is abnormal
Ventricles are typically smooth-walled
Cavum septum pellucidum is abnormal
Falx may be abnormal
Other CNS abnormalities may be visible (e.g. fused frontal horns)
Destructive - infarcts, bleeds, infections, trauma
Ventricle position is normal
Thinning/loss of cerebral cortex in a patchy asymmetric distribution
Midline structures are normal
Posterior fossa structures are normal
Falx is present
MRI Brain
Metabolic workup - normal peroxisomal panel and sterol panel
CPK ranged from 2,000 to 23,280
Sent microarray for congenital muscular dystrophy panel…
Pt homozygous for POMT1 gene
- for a sequence variant causing a frame-shift mutation
- located on 9q34.13
- Defective glycosylation of alpha-dystroglycan complex (in skeletal
muscle works as a transmembrane linkage between extracellular
matrix and the cytoskeleton. In brain, impairs interaction of
migrating neurons with matrix elements, causing malformations of
cortical development.
- Dystroglycan also found in other tissues including kidneys and
Walker-Warburg Syndrome
- AKA Muscle-Eye-Brain Disease
- Autosomal recessive - 25% chance of having another child with WWS
- Life expectancy 4 months (but variable phenotypes and severities depending
on exact mutation)
- Can include macro or microcephaly, eye malformations (retinal dysplasia,
ocular colobomas, cataracts), brain malformations (hydrocephalus,
lissencephaly type II, Dandy-Walker, cerebellar malformations,
encephalocele, agenesis of the corpus callosum), congenital muscular
Expected pathology
- Gross pathology: CNS structural abnormalities including cobblestoning of
lissencephaly type II
- Micro: Type II lissencephaly: Chaotic neuronal organization, interrupted glia,
allowing passage of neurons into subarachnoid space
- Muscle biopsy usually shows dystrophic changes. Immunohistochemistry
shows deficient alpha-dystroglycan with normal dystrophin
Virtual Microscopy
Cortex Slide A
Cortex Slide B
Cerebellum Slide F
Spinal Cord Slide J
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