Developmental Diseases of the NS Flashcards
Marked enlargement of one cerebral hemisphere as a result of a developmental abnormality. Usu. Cognitively delayed. Some have epilepsy.
Hemimegalencephaly
There are individuals whose heads and brains are enlarged but who are normal in all other respects. This has been shown to be inherited in what pattern?
Autosomal dominant
Common congenital defect associated with macrocephaly, varying degrees of mental impairment, optic defects and seizures and on CT is revealed as a “bat-wing” deformity of the ventricles.
Agenesis of the corpus callosum.
Most severe and lethal of the craniostenoses.
Clover-shaped skull
Two genetic variations of Down Syndrome
- Triplication of Chromosome 21
2. Translocation therefore duplication of distal portion of long arm of chromosome 21
H3O mnemonic for Prader-Willi Syndrome and associated genetic defect
Hypotonia
Hypomentia
Hypogonadism
Obesity (from hyperphagia)
Microdeletion 15q11-q13
70% noninherited deletion from paternl X chromosome
Syndrome that is associated with an identical chromosomal abnormality to that of Prader-Willi syndrome but maternally inherited, presenting with developmental delay, microcephaly, refractory seizures inappropriate laughter, absence of speech ataxia, prominent jaw, thin upper lip
Angelman syndrome
Most common anomaly attributable to anticonvulsant drugs
Cleft lip and palate
Others reported: Craniofacial defects Spina bifida Minor cardiac defects Dysraphisms
Features the phakomatoses have in common
- Hereditary transmission
- Involves organs of ectodermal origin
- Slow evolution of lesions in childhood and adolescence
- Tendency to form hamartomas
- Disposition to fatal malignant transformation
Characteristic triad of Tuberous Sclerosis?
Two diagnostic dermal features of the disease?
Adenoma sebaceum, Epilepsy & developmental delay
“Ash-leaf” lesions - hypomelanotic skin macules
Subepidermal fibrotic Shagreen patch
Genetic abnormality in Tuberous Sclerosis?
In one of the ff:
TSC1 (hamartin) on long arm of chromosome 9
TSC2 (tuberin) on short arm of chromosome 16
Lesion pathognomonic of Tuberous Sclerosis
Adenomas of Pringle - well-developed facial lesions angiofibromas, red to pink nodules with smooth glistening surface limited to nasolabial folds, cheeks, chin (occ forehead and scalp)
Radiologic surveillance to detect enlargement of subependymal tumors in Tuberous Sclerosis
Annually for <21y
Then every 2-3yrs after
Symptom common in adults with NF1 often related to a malignant peripheral nerve sheath tumor
Pain
This distinguishes molluscum fibrosum of NF1 from other skin tumors such as multiple lipoma
“buttonholing” - when pressed, these soft tumors tend to invaginate through a small opening in the skin
Defective protein in Ataxia-Telangiectasia. Absent in 90% of those with the disease
ATM protein - a kinase that’s a transducer in the pathway for DNA repair that halts the cell cycle after DNA damage
Ataxia-Telangiectasia or Louis-Bar syndrome
Autosomal recessive
Progressive ataxia with humoral immune deficiency and telangiectasia
Two mutant genes identified as causes of the Osler-Rendu-Weber Disease
endoglin
novel kinase
Causative mutation and pattern of inheritance of von Hippel-Lindau disease
Mutation in the VHL gene on chromosome 3
Autosomal dominant with variable but high penetrance by older age
Characteristic finding of Sturge Weber Syndrome on Skull films taken after the 2nd year
“tramline” calcification which outlines the involved convolutions of the parietooccipital cortex
Hutchinson triad
Dental deformities
Interstitial keratitis
Bilateral deafness
Seen albeit infrequently in its complete form in congenital syphilis
An acoustic neuroma developing before this age should be suspected to be caused by NF2
Before 30yrs
What is a stacked arrangement of two rows of elongated palisading nuclei that alternates with acellular zones made up of cytoplasmic processes? In which tumor is this seen? A. Schwannoma B. Neurofibroma C. Both D. None of the above
Verocay body
C. Seen in both schwannoma and neurofibroma
A polymorphism in this gene is seen in almost 90% of patients with the Sturge-Weber trait and a similar # of patients with non-syndromic port-wine stains on the cranium
GNAQ
Whitish, marble-like appearance of the putamen, thalamus and border zones of the cerebral cortex that is the most frequent pathologic finding in the brain after insult to the infant brain
Status marmoratus or état marbré
Whitish strands - nerve cell loss and gliosis
Condensation - bands of traversing myelinated fibers
Pathologic changes of symmetrically distributed nerve cell loss and gliosis and unique yellow staining of nuclear masses from hyperbilirubinemia in kernicterus spare the what areas?
Hippocampus
Immature cerebral cortex
Target serum bilirubin level in the treatment of erythroblastosis fetalis that would allow the nervous system to escape perinatal damage
Keep blood bilirubin to less than 20mg/dL in term infants, <10mg/dL in premature infants
Until this age of gestation, large microbial organisms such as bacteria, spirochetes, protozoa, fungi, are unable to invade the embryo
3rd - 4th month of gestation
Times the ff organisms are able to invade the developing embryo A. Rubella B. CMV C. HIV D. HSV2 E. Treponema pallidum F. Toxoplasma G. Listeria monocytogenes
A. Rubella - first 10wks AOG (up to 24th wk AOG)
B. CMV - 1st trimester, during delivery, breastfeeding
C. HIV - 1st trimester, during delivery, breastfeeding
D. HSV2 - during delivery
E. Treponema pallidum - 4th to 7th mos AOG
F. Toxoplasma - late in the gestational period
G. Listeria monocytogenes - during delivery or in utero from maternal and fetal septicemia
What drug may be used to prevent fetal infection from mothers who develop toxoplasma antibodies in the first 2-3 mos of pregnancy?
Once fetus is infected, what drug should be used?
Spiramycin (Rovamycine)
If fetus infected - use pyrimethamine and sulfadiazine
Cerebral calcifications are present mainly in both Congenital Toxoplasmosis and CMV infections, how can the two be differentiated on imaging?
Toxoplasma- widely disseminated cerebral calcifications
CMV - calcifications are periventricular
Pregnant mothers with syphilis must be treated before what month to prevent infection of the fetus?
Before the 4th month AOG
Transmission occurs at any time from the 4th to 7th months
In which congenital viral infection can a second child be infected?
CMV
Genetic abnormality in the Fragile X syndrome
Unstable inherited CGG repeating sequence at the distal end of the long arm of the X chromosome
The Fragile X premutation syndrome may be manifest in adult women as
Premature ovrian failure
