Progeria

Progeria

A rare genetic disorder that causes children to age prematurely. The classic type of childhood progeria is Hutchinson-Gilford syndrome, which is commonly referred to as progeria.The word Progeria comes from the Greek progeros meaning ‘prematurely old’. The Greek word pro means ‘before’, while the word geras means ‘old age’ .

PROGERIA

Hutchinson–Gilford progeria syndrome

A rare genetic disorder that causes children to age prematurely. The classic type of childhood progeria is Hutchinson-Gilford syndrome, which is commonly referred to as progeria.The word Progeria comes from the Greek progeros meaning ‘prematurely old’. The Greek word pro means ‘before’, while the word geras means ‘old age’ . The disorder has very low incidences and occurs in one per eight million live births.  Those born with progeria typically live about thirteen years, although many have been known to live into their late teens and early twenties and rare individuals may even reach their forties

Symptoms

* Growth failure during the first year of life

* Narrow, shrunken or wrinkled face

* Baldness

* Loss of eyebrows and eyelashes

* Short statureShort stature

* Large head for size of face (macrocephalymacrocephaly)

* Open soft spot (fontanelle)

* Small jaw (micrognathiamicrognathia)

* Dry, scaly, thin skin

* Limited range of motionLimited range of motion

* Teeth – delayed or absent formation

Causes

It is a genetic condition that occurs as a new mutation and is not usually inherited, although there is a uniquely heritable form. This is in contrast to another rare but similar syndrome, dyskeratosis congenita (DKC), which is inheritable and will often be expressed multiple times in a family line.

Hutchinson-Gilford progeria syndrome (HGPS) is a childhood disorder caused by a point mutation in position 1824 of the LMNA gene, replacing cytosine with thymine, creating an unusable form of the protein Lamin A. Lamin A is part of the building blocks of the nuclear envelope.

Progeria is due to a single-letter “misspelling” in a gene on chromosome 1 that codes for lamin A, a protein that is a key component of the membrane surrounding the cell’s nucleus. Most children with classic progeria harbor exactly the same misspelling in the lamin A (LMNA) gene, a substitution of just a single DNA base — a change from cytosine (C) to thymine (T) — among the gene’s 25,000 base pairs. In a few progeria patients there may be a different single base substitution such as guanine (G) to adenine (A) just two bases upstream. In every instance, the parents are normal indicating that the misspelling is a new, or “de novo,” mutation in the child. The minute change in the LMNA gene changes the way in which the sequence is spliced by the cell’s protein-making machinery. The end result is the production of an abnormal lamin A protein that is missing a stretch of 50 amino acids near one of its ends.

The signs include:

* Insulin-resistant diabetesdiabetes (diabetes that does not respond readily to insulin injections)

* Skin changes similar to that seen in scleroderma (the connective tissue becomes tough and hardened)

Cardiac stress testing may reveal signs of early atherosclerosis of blood vessels.

Genetic testing can detect mutations in lamin A that cause progeria.

Prognosis

There is no known cure. Few people with progeria exceed 13 years of age.  At least 90% of patients die from complications of atherosclerosis, such as heart attack or stroke.

Mental development is not affected. The development of symptoms is comparable to aging at a rate eight to ten times faster than normal, although certain age-related conditions do not occur

Progeria is associated with a short lifespan. The average patient survives to the early teens. However, some patients can live up to 30 years. The cause of death is usually related to the heart or a strokestroke as a result of the progressive atherosclerosis.

TREATMENT

There is no treatment for this disease but many measures can reduce its complications such as by-pass surgery to reduce cardiovascular problem , disorders of respiration and arthritis.  In some cases hormone treatment is done to reduce the complication associated with Progeria

Certain therapies may ease some of the signs and symptoms.

They include:

* Low-dose aspirin. A daily dose may help prevent heart attacks and stroke.

* Physical and occupational therapy. These may help with joint stiffness and hip problems, and may allow your child to remain active.

* High-calorie dietary supplements. Including extra calories in your child’s daily diet may help prevent weight loss and ensure adequate nutrition.

* Feeding tube. Infants who feed poorly may benefit from a feeding tube and a syringe. You can use the syringe to push pumped breast milk or formula through the tube to make it easier for your child to feed.

* Extraction of primary teeth. Your child’s permanent teeth may start coming in before his or her baby teeth fall out. Extraction may help prevent problems associated with the delayed loss of baby teeth, including overcrowding and developing a second row of teeth when permanent teeth come in.

Drugs known as farnesyltransferase inhibitors (FTIs), which were developed for treating cancer, have shown promise in laboratory studies in correcting the cell defects that cause progeria. FTIs are currently being studied in human clinical trials for treatment of progeria