Discussion in 'Spot Diagnosis' started by Egyptian Doctor, Oct 20, 2012.
What is your medical diagnosis ?
Beckwith Wiedemann syndrome
Answer : Beckwith Wiedemann syndrome
I don't want to be seen as looking smart in hindsight, but full credit to both the respondents. The image of the child gives very little away ( no apparent hemihypertrophy (except may be left side of the face) - that coould point towards the diagnosis ). The image of the ear was supposed to hold the key
Stefan gave a good shot with CHARGE syndrome, but in CHARGE syndrome the ear is typically bowl shaped (lop ears )
The grooves in the image are characteristic for - Beckwith-Wiedemann syndrome.
Thanks again to Egyptian doctor for throwing up this interesting challenge !
the main gene involved in - Beckwith-Wiedemann syndrome is IGF-2 and a question on it's genetics is usually asked in highly competitive exams like the USMLE step 1 and is put in as a discriminator to determine who ends up with top scores. I will put in such discriminator questions wherever I see an opportunity ( in the interest of those who are going to face the exam ) (-:
Cancers may be caused by mutations in two types of genes, those that affect cell proliferation (oncogenes, tumor suppressor genes) and those that control rates of mutation (caretaker genes—i.e., those altering DNA repair). A child develops a wide gait and is found to have different leg lengths. On examination, one leg is larger (hemihypertrophy) and a mass is found in the lower abdomen. Surgery reveals a Wilms tumor, and the IGF2 (insulin-like growth factor 2) gene is known to be specifically overexpressed in Wilms tumor. Restriction analysis of the child's tumor DNA showed that both IGF2 alleles were undermethylated. It is known that normal adult tissues have one methylated and one undermethylated IGF2 allele, while the single IGF2 allele in sperm DNA is always undermethylated. The results are best summarized as which of the following?
A. A loss of imprinting (LOI) mutation that increased tumor IGF2 expression and identifies IGF2 as a caretaker gene
B. A loss of imprinting (LOI) mutation that increased tumor IGF2 expression and identifies IGF2 as an oncogene
C. A loss of imprinting (LOI) mutation that increased tumor IGF2 expression and identifies it as a tumor suppressor gene
D. A loss of imprinting (LOI) mutation that increased tumor IGF2 expression and causes Wilms tumor in females only
E. A loss of imprinting (LOI) mutation that increased tumor IGF2 expression and causes Wilms tumor in males only
[FONT=&]EXPLANATION:[/FONT][FONT=&] The undermethylation of IGF2 alleles in sperm as compared to methylated and undermethylated alleles in diploid adult tissues suggests that the gene is imprinted. During germ cell formation, certain chromosome regions are patterned differently or "imprinted" in males versus females, producing different levels of maternal versus paternal allele expression in tissues of the resulting embryos and adults. These imprinting patterns are associated with DNA methylation at key CpG dinucleotide sites, up- or down-regulating allele transcription and expression. Biparental origin of alleles in diploid tissues is thus necessary for normal levels of gene expression, a balance disrupted by uniparental disomy (both copies of a chromosome and its alleles from one parent) or loss of imprinting (LOI) of one allele. Imprinted genes are often growth factors, perhaps arising to regulate embryofetal growth but persisting in diploid tissues as potential sources of cell proliferation and tumors. The specific increased IGF2 expression in WIlms tumor suggests it is a potential regulator of cell proliferation rather than rates of mutation. The fact that one allele can increase expression and cause a tumor suggests IGF2 is an oncogene rather than a tumor suppressor that must have both alleles inactivated to produce a tumor.[/FONT]
[FONT=&]The answer is B.[/FONT]
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