 What is progeria.  Incidence.  Epidemiology.  Signs and symptoms.  Causes.  Diagnosis.  Prognosis.  Treatments.

 The word ‘pro’ means before or premature, ‘geria’ means old age.  Progeria is also known as Hutchinson-Gilford Progeria Syndrome (HGPS)  It is a rare and very fatal genetic condition  Premature aging.  Classical Huchinson-Gliford progeria syndrome is usually caused by a sporadic mutation taking place during the early stages of embryo development.

 Progeria is listed as a rare disease by the Office of Rare Disease (ORD) of the National Institutes of Health (NIH).  Progeria affects all races with about 97% of the children affected being Caucasian.  Also, it affects both sexes almost equally with the slightly male predilection; the male-to-female ratio is 1.5:1.  In the pass 15 years children with progeria have been reported all over the world.

 A study from Netherlands has shown an incidence of 1 in 4 million births, currently there are 100 known cases in the world. Approximately 140 cases have been reported in medical history. However the Progeria Research Foundation believes there may be as many as 150 undiagnosed cases worldwide.

 There have been only two cases in which a healthy person was known to carry the LMNA mutation that causes progeria. These carriers was identify because they pass it on to their children.  The first reported case of a black child with progeria was identified in September 2011.

 Beginning around a year and a half to two years of age children show signs of accelerated aging  Growth Failure  Loss of body fat  Loss of hair(alopecia)  Aged skin  Stiff joints  Hip dislocation  Atherosclerosis  Heart disease  Stroke

 Small face and jaw  Pinched nose  Mental development is not affected  No neurodegeneration  No cancer predispositions  Age at a rate 6-8 times faster than normal

 Progeria usually only allows a child to live to be on average 13 years  Most cases of death is caused by atherosclerosis  Can die as young as 8  Oldest lived to be 29

 Progeria is thought to be a dominant trait and it is developed during cell division of a newly conceived child.  It also can take place in the gamete of one of the parents.

 A mutation in the LMNA gene (produces lamin A protein).  Located on chromosome 1.  This protein is what holds the cells nucleus together.  When this protein is defected it makes the nucleus unstable.  This is the process that leads to premature aging.

 Out of 664 Amino acids coding for the lamin A protein the mutation occurs in 50 of them.  Happens in exon 11.  This is a defect in the splicing.  There has not been enough information obtained on this so no image of the protein or mutation of the protein are available.

 Prelamin is when the protein is entering through the membrane  The prelamin is supposed to be cleaved off and detached from the membrane to form the lamin A protein that needs to be around the nucleus C Terminal globular domain The mutation happens after this globular domain

 The LMNA gene provides instructions for making a protein called lamin A. This protein plays an important role in determining the shape of the nucleus within cells. It is an essential scaffolding (supporting) component of the nuclear envelope, which is the membrane that surrounds the nucleus.

 The altered protein makes the nuclear envelope unstable and progressively damages the nucleus, making cells more likely to die prematurely. result in the production of an abnormal version of the lamin A protein.

 Diagnosis is suspected according to signs and symptoms, such as;  Skin changes.  Abnormal growth.  And loss of hair.  A genetic test for LMNA mutations can confirm the diagnosis of progeria.

 Parental diagnosis and PGD for risk at-risk pregnancies require prior identification of the disease-causing mutation in the family.  Of note, reoccurrence within a family is rare given that most mutation are de novo and germ line mosaicism is rare.

 Make sure the child stays well hydrated.  Provide frequent, small meals.  Provide opportunities for regular physical activity.  Get cushioned shoes or shoe inserts for the child.  Provide learning opportunities.

 Make sure the child is up to date on childhood.

 As there is no known cure, few people with progeria exceed 13 years age. At least 90% of patients die from complications of atherosclerosis, such as heart attacks or stroke.  Mental development is not adversely affected; in fact, intelligence tends to be normal to above average.

 With respect to the features of aging that progeria appears to manifest, the development of symptoms is comparable to aging at a rate eight to ten times faster than normal. Although there are may not be any successful treatments for progeria itself, there are treatments for the problems it causes, such as arthritic, respiratory, and cardiovascular problems.

 No treatment has proven effective.  Most treatment focuses on reducing complications (such as cardiovascular disease) with coronary artery bypass surgery or low-dose aspirin.  Physical and occupational therapy; these may help with joint stiffness and hip problems and may allow the child to remain active.

 Extraction of primary teeth; extraction may help prevent problems associated with the delayed loss of baby teeth,other medications; depending on the child’s condition, doctor may prescribe other medications, anticoagulants to help prevent blood clots. The use of growth hormone may help increase height and weight.

  www. progeria research.org   outreach/2_entrez/2ENTREZ_Index.htm