02 May 2009

Common Genetics Problems in Pediatrics



Common Genetics Problems in Pediatrics
Presentation lecture by:Shannon Browning MD

Klinefelter Syndrome

* Occurs in approximately 1 in 1000 births
* 80% have the classic 47,xxy karyotype, with 10 % having 46,XY/47XXY mosaicism and another 10% having multiple x or Y chromosomes
* Results from nondisjunction and is often associated with advanced maternal age
* Rarely diagnosed before the onset of puberty
* Most children with KS present initially with behavior problems , abnormal puberty or infertility issues
* Typically taller than average and increased carrying angle and a relatively wide pelvis
* 30% will develop gynecomastia during in puberty
* 50% of children have speech delays and 25% have motor
* All affected males are infertile, although there are rare cases of fertility

Sickle Cell Disease

* Results from a single genetic mutation in which a nucleotide in the coding sequence of a beta-globin gene is mutated from adenosine to thymidine
* This mutation occurs in the middle of the triplet that codes for normally glutamic acid as the 6th AA of the beta-chain of hemoglobin. The single base change substitutes Valine for glutamic acid.
* The resulting mutated hemoglobin has decreased solubility and abnormal polymerization properties
* If only 1 beta-globin gene is mutated= heterozygous state which is referred to as sickle cell trait
* If both genes are mutated resulting in homozygous state and called sickle cell anemia or sickle cell disease.
* Prenatal testing for sickle cell has improved significantly over the past 2 decades.
* The newborn with sickle cell disease is not anemic initially because of the protective affects of elevated fetal hemoglobin. Hemolytic anemia develops over the 1st 2-4mo.
* Chorionic villus sampling can be performed as early as 9 wks gestation making it an earlier alternative to amniocentesis.

Teratogens

* Accutane embryopathy is associated with embryonic exposure to isotretinoin beyond the 15th day after conception and through the end of 1st trimester
* Isotretinoin is a vitamin A derivative that is administered orally and used for the treatment of cystic acne
* It impedes the normal neural crest migration in the developing embryo.
* This disruption in the migration of the neural crest cells leads to defects in the central nervous system, severe ear anomalies, conotruncal heart defects and thymic abnormalities
* Alcohol can cause all the above mentioned abnormalities with the exception of thymus abnormalities
* Warfarin embryopathy is a recognizable pattern of malformation. Warfarin acts as an anticoagulant because it is a vitamin K antagonist. It prevents the carboxylation of gamma-carboxyglutamic acid which is a component of osteocalcin and other vit K dependent bone proteins.
* The critical period of exposure is between 6-9 weeks.

Down’s Syndrome

* 95% of all those affected with DS have trisomy of the chromosome 21
* 90-95% of these cases are due to maternal meiotic error with 75% occurring in meiosis I. 3-5% are due to paternal meiotic errors and the remainder are due to mitotic nondisjunction
* Recurrence risk estimates are based on empiric data
* The overall recurrence risk for having a child with any trisomy is approx 1% added to the mother’s age-related risk. As a woman ages the age related risk exceeds the recurrence risk

Turner Syndrome

* The two most common features in girls with TS is short stature and gonadal dysgenesis. It should be suspected in any girl of short stature with unknown cause.
* Estimated that 1 in 2500 girls are affected
* Linear growth velocity varies: from birth to 3 yrs it is normal, from 3-12 yrs velocity decreases, and after age 12 it decelerates even further.
* Most affected girls have a 45,X karyotype
* Diagnosis is based on chromosomal analysis

Neurofibromatosis Type I

* Occurs in 1 in 3000 to 1 in 4000 lives births and is unrelated to gender, ethnicity or geographic location
* Autosomal dominant condition
* 50% of cases are spontaneous mutations in the gene that codes for neurofibromin on chromosome 17.
* Males and females are equally affected
* The recurrence risk to offspring of an affected individual is 50%
* This gene abnormality shows full penetrance
* Café au lait macules (CALMs) are uniformly pigmented flat spots that range in size from a few mm to as much as 30cm in adults. CALMs increase in size in proportion to growth.
* One or two CALMs are common more than 6 raises the concern about NF-1
* Of children who present with 6 or more CALMs 89% meet the diagnostic criteria for NF-1 within 3 years.

Angelman Syndrome

* Affected children are normal at birth
* They experience global developmental delay, but speech is affected most. Most children will never speak
* They laugh frequently and have an ataxic gait and often hold their elbows away from their bodies.

Common Genetics Problems in Pediatrics.ppt

0 comments:

All links posted here are collected from various websites. No video or powerpoint files are uploaded on this blog. If you are the original author and do not wish to display your content on this blog please Email me anandkumarreddy at gmail dot com I will remove it. The contents of this blog are meant for educational purpose and not for commercial use. If you use any content give due credit to the original author.

This site uses cookies from Google to deliver its services, to personalise ads and to analyse traffic. Information about your use of this site is shared with Google. By using this site, you agree to its use of cookies.

  © Blogger templates Newspaper III by Ourblogtemplates.com 2008

Back to TOP