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Gorlin syndrome

Alternative Names:Nevoid basal cell carcinoma syndrome (NBCCS),basal cell nevus syndrome, multiple basal cell carcinoma syndrome and Gorlin–Goltz syndrome

Definition:–
Gorlin syndrome is an inherited medical condition involving defects within multiple body systems such as the skin, nervous system, eyes, endocrine system, and bones. People with this syndrome are particularly prone to developing a common and usually non-life-threatening form of non-melanoma skin cancers.

You may click to see more pictures of  Gorlin syndrome

People with the syndrome have a predisposition to multiple basal cell carcinomas (a form of skin cancer), jaw cysts and other generally harmless abnormalities in the bone. The severity of the disease can be wide-ranging.

About 10% of people with the condition do not develop basal cell carcinomas (BCCs). the name Gorlin syndrome refers to researcher Robert J. Gorlin (1923–2006).

First described in 1960, NBCCS is an autosomal dominant condition that can cause unusual facial appearances and a predisposition for basal cell carcinoma, a malignant type of skin cancer. The prevalence is reported to be 1 case per 56,000-164,000 population. Recent work in molecular genetics has shown NBCCS to be caused by mutations in the PTCH (Patched) gene found on chromosome arm 9q. If a child inherits the defective gene from either parent, he or she will have the disorder

Incidence:–
About 750,000 new cases of sporadic basal cell carcinomas (BCCs) occur each year in the United States. Ultraviolet (UV) radiation from the sun is the main trigger of these cancers, and people with fair skin are especially at risk. Most sporadic BCCs arise in small numbers on sun-exposed skin of people over age 50, although younger people may also be affected. By comparison, NBCCS has an incidence of 1 in 50,000 to 150,000 with higher incidence in Australia. One aspect of NBCCS is that basal cell carcinomas will occur on areas of the body which are not generally exposed to sunlight, such as the palms and soles of the feet and lesions may develop at the base of palmer and plantar pits. One of the prime features of NBCCS is development of multiple BCCs at an early age, often in the teen years. Each person who has this syndrome is affected to a different degree, some having many more characteristics of the condition than others.

Components:-
Some or all of the following may be seen in someone with Gorlin Syndrome:

1.Multiple basal cell carcinomas of the skin
2.Odontogenic keratocyst: Seen in 75% of patients and is the most common finding. There are usually multiple lesions found in the mandible. They occur at a young age (19 yrs average).
3.Rib and vertebrae anomalies
4.Intracranial calcification
5.Skeletal abnormalities: bifid ribs, kyphoscoliosis, early calcification of falx cerebri (diagnosed with AP radiograph)
6.Distinct faces: frontal and temporopariental bossing, hypertelorism, and mandibular prognathism

What genes are related to Gorlin syndrome?
Mutations in the PTCH1 gene cause Gorlin syndrome. This gene provides instructions for making a protein called Patched-1, which functions as a receptor. Receptor proteins have specific sites into which certain other proteins, called ligands, fit like keys into locks. Together, ligands and their receptors trigger signals that affect cell development and function. A protein called Sonic Hedgehog is the ligand for the Patched-1 receptor. Patched-1 prevents cell growth and division (proliferation) until Sonic Hedgehog is attached.

The PTCH1 gene is a tumor suppressor gene, which means it keeps cells from proliferating too rapidly or in an uncontrolled way. Mutations in this gene prevent the production of Patched-1 or lead to the production of an abnormal version of the receptor. An altered or missing Patched-1 receptor cannot effectively suppress cell growth and division. As a result, cells proliferate uncontrollably to form the tumors that are characteristic of Gorlin syndrome.

You may click to learn more about the PTCH1 gene.

How do people inherit Gorlin syndrome?
Gorlin syndrome is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the features that are present from birth, such as large head size and skeletal abnormalities. An affected person often inherits a PTCH1 mutation from one affected parent. Other cases may result from new mutations in the gene. These cases occur in people with no history of the disorder in their family. For tumors to develop, a mutation in the other copy of the PTCH1 gene must occur in certain cells during the person’s lifetime. Most people who are born with one PTCH1 mutation eventually acquire a second mutation in certain cells and develop basal cell carcinomas and other tumors.

Causes:-
Gorlin syndrome is an autosomal dominant condition. The abnormal gene is found on chromosome 9. New mutations (where neither parent carries the gene) are common.

Diagnosis:–
Diagnosis of NBCCS is made by having 2 major criteria or 1 major and 2 minor criteria.

The major criteria consist of the following:

1.more than 2 BCCs or 1 BCC in a person younger than 20 years;
2.odontogenic keratocysts of the jaw
3.3 or more palmar or plantar pits
4.ectopic calcification or early (<20 years) calcification of the falx cerebri
5.bifid, fused, or splayed ribs
6.first-degree relative with NBCCS.

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The minor criteria include the following:

1.macrocephaly.
2.congenital malformations, such as cleft lip or palate, frontal bossing, eye anomaly (cataract, colobma, microphtalmia, nystagmus).
3.other skeletal abnormalities, such as Sprengel deformity, pectus deformity, polydactyly, syndactyly or hypertelorism.
4.radiologic abnormalities, such as bridging of the sella turcica, vertebral anomalies, modeling defects or flame-shaped lucencies of hands and feet.
5.ovarian and cardio fibroma or medulloblastoma (the latter is generally found in children below the age of two).
People with NBCCS need education about the syndrome, and may need counseling and support, as coping with the multiple BCCs and multiple surgeries is often difficult. They should reduce UV light exposure, to minimize the risk of BCCs. They should also be advised that receiving Radiation therapy for their skin cancers may be contraindicated. They should look for symptoms referable to other potentially involved systems: the CNS, the genitourinary system, the cardiovascular system, and dentition.

Genetic counseling is advised for prospective parents, since one parent with NBCCS causes a 50% chance that their child will also be affected.

Treatment:–
Although there’s no cure, the carcinomas can be treated by surgery, lasers or photodynamic therapy, which reduces scarring.

If there’s a family history of the syndrome, it’s possible for family members to be tested to see if they carry the faulty gene.

Those with Gorlin syndrome are now advised to avoid – or to take advice before undergoing – any radiation treatment, as it’s thought it may exacerbate the condition.

Treatment is usually supportive treatment, that is, treatment to reduce any symptoms rather than to cure the condition.

*Enucleation of the odontogenic cysts can help but new lesions, infections and jaw deformity are usually a result.
*The severity of the basal cell carcinoma determines the prognosis for most patients. BCCs rarely cause gross disfigurement, disability or death .

*Genetic counseling

Advice and support:-
•Gorlin Syndrome Group
•Tel: 01772 496849
•Email: info@gorlingroup.org
•Website: www.gorlingroup.org

Disclaimer: This information is not meant to be a substitute for professional medical advise or help. It is always best to consult with a Physician about serious health concerns. This information is in no way intended to diagnose or prescribe remedies.This is purely for educational purpose.

Resources:
http://www.bbc.co.uk/health/physical_health/conditions/gorlinsyndrome1.shtml
http://en.wikipedia.org/wiki/Nevoid_basal_cell_carcinoma_syndrome
http://ghr.nlm.nih.gov/condition/gorlin-syndrome
http://dermnetnz.org/systemic/gorlins.html

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Goldenhar syndrome

Alternative Names:Oculoauriculo-vertebral spectrum(OAV).

Definition:
Goldenhar syndrome is a rare congenital defect characterized by incomplete development of the ear, nose, soft palate, lip, and mandible. It is associated with anomalous development of the first branchial arch and second branchial arch. Common clinical manifestations include limbal dermoids, preauricular skin tags, and strabismus.It  is a highly complex combination of malformations which leaves babies with an underdeveloped face.

YOU MAY CLICK TO SEE THE PICTURE…

The term is sometimes used interchangeably with hemifacial microsomia, although this definition is usually reserved for cases without internal organ/verterbrae disruption.

Goldenhar syndrome was first described by Dr. Maurice Goldenhar in 1952.

It affects between 1/3500 to 1/26000 live births in the UK

Symptoms:
Chief markers of Goldenhar syndrome are incomplete development of the ear, nose, soft palate, lip, and mandible on usually one side of the body. Additionally, some patients will have growing issues with internal organs, especially heart, kidneys, and lungs. Typically, the organ will either not be present on one side or will be underdeveloped. Note that whilst it is more usual for there to be problems on only one side, it has been known for defects to occur bilaterally (approximate incidence 10% of confirmed GS cases).

The main features of the condition affect the ear, which may not have developed at all. This combines with underdevelopment of the jaw and cheek on the same side of the face. When these are the only problems it is normally referred to as hemi-facial microsomia and sometimes the condition stops there. But when associated with other abnormalities, particularly affecting the vertebrae in the neck it is referred to as Goldenhar Syndrome, or ‘oculoauricular dysplasia’. Dental problems are common due to the difference between both sides of the face and the jaw bones.

Goldenhar children very occasionally have been known to have heart and kidney abnormalities.

Most individuals with the syndrome are of normal intelligence although learning difficulties can occur in about 13% of cases. However there are usually language problems as a result of deafness and there may be speech and swallowing problems.

Many babies with Goldenhar Syndrome have poor weight gain in the first year or two of life as a result of their dental abnormalities.

Other problems can include severe scoliosis (twisting of the vertebrae), limbal dermoids, and hearing loss (see hearing loss with craniofacial syndromes).Deafness/blindness in one or both ears/eyes.

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Causes:–
The cause of Goldenhar syndrome is largely unknown. However, it is thought to be multifactorial, although there may be a genetic component, which would account for certain familial patterns. It has been suggested that there is a branchial arch development issue late in the first trimester.

An increase in Goldenhar syndrome in the children of Gulf War veterans has been suggested but the difference was shown to be statistically insignificant

Diagnosis
There is not a genetic test that can diagnose Goldenhar syndrome. The diagnosis is made when an individual has the common symptoms associated with the condition. The diagnosis is made by a physician.

Treatment :
Once a child is diagnosed with Goldenhar syndrome, additional tests should be performed. A hearing evaluation is necessary to determine if there is hearing loss. If hearing loss is evident, the child should be referred to a hearing specialist. Speech therapy may also be helpful. X rays of the spine are recommended to determine if there are vertebral problems, and the severity. Individuals with Goldenhar syndrome should also be regularly evaluated for scoliosis. Renal ultrasounds and ultrasounds of the heart may also be recommended, due to the increased risk for birth defects in these areas. A doctor would make this recommendation. Finally, individuals with Goldenhar syndrome should be evaluated by an eye doctor (ophthalmologist).

 CLICK & SEE

Surgery may be required to correct the birth defects seen in Goldenhar syndrome. Surgery to correct the facial birth defects can improve appearance and function.

It is necessary to help the child to develop e.g. jaw distraction/bone grafts, occular dermoid debulking, repairing cleft palate/lip, repairing heart malformations, spinal surgery. Hearing aids placed in one or both ears.

Some patients with Goldenhar syndrome will require assistance as they grow by means of hearing aids or glasses.

Prognosis
The prognosis for individuals with Goldenhar syndrome is very good. These individuals typically have a normal life span and normal intelligence.

Prevention:
There has been progress in identifying the condition through pre-natal scanning and it is thought the risk of having another affected child is small.

Disclaimer: This information is not meant to be a substitute for professional medical advise or help. It is always best to consult with a Physician about serious health concerns. This information is in no way intended to diagnose or prescribe remedies.This is purely for educational purpose.

Resources:
http://www.bbc.co.uk/health/physical_health/conditions/goldenhar_syndrome.shtml
http://www.healthline.com/galecontent/goldenhar-syndrome/3
http://en.wikipedia.org/wiki/Goldenhar_syndrome
http://confessionsofateacher.files.wordpress.com/2009/12/867477.jpg
http://www.pharmacyescrow.com/blog/index.php/2011/03/11/goldenhar-syndrome/
http://www.i-am-pregnant.com/Birth/Birth-defects/Goldenhar-SyndromeGoldenhar syndrome

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Fragile X Syndrome

Alternative Names: Martin-Bell syndrome; Marker X syndrome

Definition:-
Fragile X syndrome is a genetic condition involving changes in part of the X chromosome. It is the most common form of inherited mental retardation in males and a significant cause of mental retardation in females.

Fragile X is a family of genetic conditions, which can impact individuals and families in various ways. These genetic conditions are related in that they are all caused by gene changes in the same gene, called the FMR1 gene.

click to see the picture

Boys are usually more severely affected as they have only one X chromosome (they carry one X and one Y chromosome). Girls have a second X chromosome, which can to some extent make up for problems with the faulty one and so they may have only mild disabilities. They may also be carriers of the condition – that is, they are not affected themselves but can pass the condition on to their children.

However the genetics of fragile X are actually more complicated as some people only have a small change called a premutation in the FMR1 gene. While they don’t usually have problems from this , it makes the gene unstable and can develop into a full mutation when passed on to the next generation.

Fragile X affects about one in 3,600 men and one in 4,000 to 6,000 women of all races and ethnic groups. It shows an X-linked recessive pattern of inheritance and changes in the gene can become more serious as it’s passed from parent to child (especially when it is passed from a woman who carries it to her child).

Some people with a permutation of FMR1 may have no, or minimal, fragile X symptoms. But those with full mutation, where larger changes in the gene exist, demonstrate more severe signs of the condition.

click to see

Despite being carriers, some men aren’t affected (even though they have no normal copy of their X chromosome). But men who have the full mutation are almost always affected.

In women with the full mutation, a third have a below-normal IQ, a third have a borderline-normal IQ and the remaining third have a normal IQ

Fragile X includes:
fragile X syndrome (FXS), the most common cause of inherited mental impairment. This impairment can range from learning disabilities to more severe cognitive or intellectual disabilities. (Sometimes referred to as mental retardation.) FXS is the most common known cause of autism or “autistic-like” behaviors. Symptoms also can include characteristic physical and behavioral features and delays in speech and language development.

fragile X-associated tremor/ataxia syndrome (FXTAS), a condition which affects balance, tremor and memory in some older male gene carriers.

fragile X-associated primary ovarian insufficiency (FXPOI), a problem with ovarian function which can lead to infertility and early menopause in some female gene carriers.

Some gene carriers do not exhibit any of these features. To learn more about carriers click here.

Fragile X can be passed on in a family by individuals who have no apparent signs of this genetic condition. In some families a number of family members appear to be affected, whereas in other families a newly diagnosed individual may be the first family member to exhibit symptoms.

Since 1984, The National Fragile X Foundation (NFXF) has been helping individuals with Fragile X, their families, and the professionals who work with them. As research into Fragile X continues, our understanding of who it affects and how it affects them will grow. The NFXF is committed to: 1) supporting and funding all efforts that will increase awareness, 2) improving education, 3) advancing research toward improved treatments and an ultimate cure, and 4) keeping the Fragile X community always well-informed about the progress of these efforts.

Understanding Fragile X: A short, independent film produced by Image Union at station wttw11 in Chicago. (26 min.)

Symptoms:
The main problem in fragile X is intellectual impairment. This can range from very minor, so that the person has a normal IQ and shows no sign of fragile X, to severe learning difficulties. How badly someone is affected depends on the degree of change in the gene.
Click to see the picture
*Hyperactive behavior
*Large body size
*Large forehead or ears with a prominent jaw
*Large testicles (macro-orchidism) after the beginning of puberty
*Mental retardation
*Tendency to avoid eye contact

Family members who have fewer repeats in the FMR1 gene may not have mental retardation, but may have other problems. Women with less severe changes may have premature menopause or difficulty becoming pregnant. Both men and women may have problems with tremors and poor coordination.

Causes:–
Fragile X syndrome is a genetic disorder caused by mutation of the FMR1 gene on the X-chromosome. Mutation at that site is found in 1 out of about every 2000 males and 1 out of about every 259 females. (Incidence of the disorder itself is about 1 in every 3600 males and 1 in 4000–6000 females.)

Prominent characteristics of the syndrome incl...
Prominent characteristics of the syndrome include an elongated face, large or protruding ears, and low muscle tone. (Photo credit: Wikipedia)

Click to see pictures

Normally, the FMR1 gene contains between 6–55 (29 in Robbins–Kumar pathology textbooks) repeats of the CGG codon (trinucleotide repeats). In people with the fragile X syndrome, the FMR1 allele has over 230–4000 repeats of this codon.

Expansion of the CGG repeating codon to such a degree results in a methylation of that portion of the DNA, effectively silencing the expression of the FMR1 protein.

This methylation of the FMR1 locus in chromosome band Xq27.3 is believed to result in constriction of the X chromosome which appears ‘fragile’ under the microscope at that point, a phenomenon that gave the syndrome its name.

Mutation of the FMR1 gene leads to the transcriptional silencing of the fragile X-mental retardation protein, FMRP. In normal individuals, FMRP is believed to regulate a substantial population of mRNA: FMRP plays important roles in learning and memory, and also appears to be involved in development of axons, formation of synapses, and the wiring and development of neural circuits

Possible Complications:-
Complications vary depending on the type and severity of symptoms.

*Recurrent infections in children
*Seizure disorder

Transmission:
Fragile X syndrome is an X-linked dominant condition with variable expressivity and possibly reduced penetrance.

Because males normally have only one copy of the X-chromosome, those males with significant trinucleotide expansion at the FMR1 locus are symptomatic. They are intellectually disabled and may show various physical features of the fragile X syndrome.

Females have two X-chromosomes and thus have an increased probability of having a working FMR1 allele. Females carrying one X-chromosome with an expanded FMR1 gene can have some signs and symptoms of the disorder or be normal. Although the extra X-chromosome can serve as a backup, only one X-chromosome is active in each cell due to X-inactivation.

Males with the fragile X cannot transmit it to any of their sons (since males contribute a Y-chromosome, not an X, to their male offspring), but will transmit the premutation to all of their daughters, as males contribute their X to all of their daughters. Males never transmit their full mutation (males with full mutations in their blood have premutations in their sperm), and expansion to full mutations never occurs through paternal transmission.

Females carrying one copy of the fragile X can transmit it to their sons or daughters; in this case each child has a 50% chance of inheriting the fragile X. Sons who receive the fragile X are at high risk of intellectual disability. Daughters who receive the fragile X may appear normal or they may be intellectually disabled, usually to a lesser degree than boys with the syndrome. The transmission of fragile X often increases with each passing generation. This seemingly anomalous pattern of inheritance is referred to as the Sherman paradox.

Diagnosis:
Fragile X syndrome was originally diagnosed by culturing cells in a folate deficient medium and then assessing the cultures for X-chromosome breakage by cytogenetic analysis of the long arm of the X-chromosome. This technique proved unreliable for both diagnosis and carrier testing.

The fragile X abnormality is now directly determined by analysis of the number of CGG repeats and their methylation status using restriction endonuclease digestion and Southern blot analysis.

Not everyone with fragile X syndrome has the same signs and symptoms. Even affected people in the same family don’t show the same symptoms. The signs and symptoms fall into six categories:

*Intelligence and learning
*Physical
*Social and emotional
*Speech and language
*Sensory
*Disorders commonly associated or sharing features with Fragile X

Autism and Fragile X syndrome:
Fragile X syndrome can cause a child to have autism or an Autism Spectrum Disorder (ASD) though not all children with fragile X syndrome have autism or an ASD.

For 2% to 6% of all children diagnosed with autism, the cause is the Fragile X gene mutation. Approximately one-third of all children diagnosed with fragile X syndrome also have some degree of autism. Fragile X syndrome is the most common known single gene cause of autism.

From Dr. Randi Hagerman’s statement to the United States House of Representatives Subcommittee on Health and Environment: “…Fragile X represents a portal through which we hope to view and treat a wide variety of other disorders of brain development and function. All children with autism…should be tested for Fragile X.”

Genetic mouse models of Fragile X syndrome have also been shown to have autistic-like behaviors

Treatment:
As yet there are no specific treatments or a cure for fragile X, but emotional and educational support for children and their families are vital to help them reach their best potential.

Most affected children have delayed speech and language development and specialised help from a speech and language therapist is vital. Behavioural therapy may help children and their families to cope with problems such as hyperactivity and impulsivity, and sometimes medication is tried. Behavioural therapy may also help those children who have problems developing relationships to develop social skills and to cope with stressful situations.

Some children cope in mainstream schools, sometimes with some extra help, while others need to go to a school which can provide for their special educational needs.

Prognosis:–
The outcome depends on the extent of intellectual impairment that is present as well as emotional and social skills.

Prevention:-
Genetic counseling may help both existing and prospective parents with a family history of Fragile X syndrome, or a family history of other symptoms such as tremor. Genetic testing can help determine the level of risk in these families.

Research:
Recent studies have focused on a number of critical areas. The role of FMRP’s RNA partners, many of which have now been validated through in vitro assays, is of primary importance. Also being examined is the function the various domains of FMRP, an RNA-binding protein, which is still relatively unknown. One hypothesis is that many symptoms are caused by unchecked activation of mGluR5, a metabotropic glutamate receptor, which was found in a 2007 study to contribute significantly to the pathogenesis of the disease;  this suggests that mGluR5 blockers could be used to treat fragile X syndrome

Disclaimer: This information is not meant to be a substitute for professional medical advise or help. It is always best to consult with a Physician about serious health concerns. This information is in no way intended to diagnose or prescribe remedies.This is purely for educational purpose.

Resources:
http://www.bbc.co.uk/health/physical_health/conditions/fragilex1.shtml
http://www.fragilex.org/html/what.htm
http://en.wikipedia.org/wiki/Fragile_X_syndrome
http://healthtools.aarp.org/adamcontent/fragile-x-syndrome?CMP=KNC-360I-GOOGLE-HEA&HBX_PK=fragile_x_syndrome&utm_source=Google&utm_medium=cpc&utm_term=fragile%2Bx%2Bsyndrome&utm_campaign=G_Diseases%2Band%2BConditions&360cid=SI_148902589_6495451981_1

http://drugster.info/ail/pathography/635/

http://psychology.wikia.com/wiki/Fragile_X_syndrome

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Fabry disease

Alternative Name: Fabry’s disease, Anderson-Fabry disease, angiokeratoma corporis diffusum and alpha-galactosidase A deficiency

Definition:
Fabry disease results from abnormal deposits of a particular fatty substance (called globotriaosylcera-mide) in blood vessel walls throughout the body. The primary defect which allows this to occur is the inherited deficiency of the enzyme, alpha galactosidase A, which is normally responsible for the breakdown of globotriaosylceramide

Metabolic Defect:
The body continuously performs metabolic processes which produce, recycle and remove vital compounds. In patients with Fabry disease one such common compound formed of three sugars and a fatty substance (globotriaosylceramide) does not get broken down due to the missing or non-functioning enzyme alpha galactosidase A. Since this fatty compound (lipid) is not being broken down and removed, it begins to accumulate. Thus, Fabry disease is often referred to as a “storage disorder” due to this abnormal accumulation. In patients with Fabry disease, this accumulation occurs primarily in the blood and in the walls of blood vessels. As the abnormal storage of this fatty compound increases with time, the channels of these vessels become narrowed, leading to decreased blood flow and decreased nourishment of the tissues normally supplied by these vessels. This abnormal process occurs in blood vessels throughout the body, particularly affecting vessels in the skin, kidneys, heart, brain and nervous system.

 CLICK & SEE

Disease Inheritance:
Fabry disease is an inherited disorder. The defective gene is on the X-chromosome, which is one of the two chromosomes that determine an individual’s sex. Females have two X chromosomes, one inherited from each of their parents. Males have one X chromosome inherited from their mother and one Y chromosome inherited from their father. A female with Fabry receive one X chromosome with a defective gene and one X chromosome with the normal gene, and thus often has some protection from the major manifestations of the disease. This is not always the case though as there is a high degree of variability in females. Males with Fabry disease receive only one abnormal X chromosome that contains the abnormal gene and thus express the disease.

CLICK TO SEE THE PICTURES

All male and female children of an affected female have a 50% chance of inheriting the defective gene from their mother. If the father is the one carrying the Fabry gene all female children will inherit the defective gene and all male children will not. The inheritance pattern of Fabry disease is called X-linked inheritance. Fabry disease occurs in all ethnic groups. It is estimated that one person in 40,000 has Fabry disease.

Symptoms:–
Symptoms are typically first experienced in early childhood and can be very difficult to understand; the rarity of Fabry disease to many clinicians sometimes leads to misdiagnoses. Manifestations of the disease usually increase in number and severity as an individual ages.

Pain
Full body or localized pain to the extremities (known as acroparesthesia) or GI tract is common in patients with Fabry disease. Acroparesthesia in Fabry disease is believed to be related to the damage of peripheral nerve fibers that transmit pain. GI tract pain is likely caused by accumulation of lipids in the small vasculature of the GI tract which obstructs blood flow and causes pain.

Renal involvement
Kidney complications are a common and serious effect of the disease; renal insufficiency and renal failure may worsen throughout life. Proteinuria (which causes foamy urine) is often the first sign of kidney involvement. End stage renal failure in males can typically occur in the third decade of life, and is a common cause of death due to the disease.

You may click to see different pictures of  Fabry disease

Cardiac manifestations
Cardiac complications occur when glycolipids build up in different heart cells; heart related effects worsen with age and may lead to increased risk of heart disease. Hypertension (high blood pressure) and cardiomyopathy are commonly observed.

Dermatological manifestations
Angiokeratomas (tiny, painless papules that can appear on any region of the body, but are predominant on the thighs, around the belly-button, buttocks, lower abdomen, and groin) are a common symptom.

Anhidrosis (lack of sweating) is a common symptom, and less commonly hyperhidrosis (excessive sweating).

Additionally, patients can exhibit Raynaud’s disease-like symptoms with neuropathy (in particular, burning extremity pain).

Ocular manifestations
Cosmetic ocular involvement may be present showing cornea verticillata (also known as vortex keratopathy), i.e. clouding of the corneas. Keratopathy may be the presenting feature in asymptomatic carriers, and must be differentiated from other causes of vortex keratopathy (e.g. drug deposition in the cornea). This clouding does not affect vision.

CLICK & SEE

Other ocular findings that can be seen include conjunctival aneurysms, posterior spoke-like cataracts, papilloedema, macular edema, optic atrophy and retinal vascular dilation.

Other manifestations;
Fatigue, neuropathy (in particular, burning extremity pain), cerebrovascular effects leading to an increased risk of stroke, tinnitus (ringing in the ears), vertigo, nausea, inability to gain weight, chemical inbalances, and diarrhea are other common symptoms.

Causes:
Fabry disease is a type of lipid storage disease caused by a defect in the gene that controls an enzyme called alpha-galactosidase A (also known as ceramide trihexosidase). This enzyme is involved in the breakdown of certain lipids (fats).

The deficiency in this enzyme causes certain lipid molecules, called glycosphingolipids, to accumulate in the body’s tissues, particularly the heart, kidneys, eyes and nerve tissue.

The gene that’s altered is on the X chromosome, making its transmission X-linked. So boys have a 50 per cent chance of inheriting the disorder, while girls have a 50 per cent chance of becoming a carrier. The gene responsible can be detected.

Diagnosis:–
Fabry disease is indicated when associated symptoms are present, and can be diagnosed by a blood test to measure the level of alpha-galactosidase activity, however this may be misleading in female carriers due to the random nature of X-inactivation. Chromosomal analysis of the GLA gene is the most accurate method of diagnosis, and many mutations which cause the disease have been noted. Kidney biopsy may also be suggestive of Fabry Disease if excessive lipid buildup is noted.

You may click to see :Final Diagnosis — Fabry’s Disease

Naturally, alpha-galactosidase A (a-GAL A) is likely to be present only at very low levels in the blood, particularly in males. In females, owing to X-inactivation patterns, levels are commonly normal even if the patient is not asymptomatic. The Sifap (stroke in young Fabry patients) project will investigate the relation between stroke and Fabry’s disease.

Misdiagnosis of Fabry Disease:  Pediatricians as well as internists commonly misdiagnose Fabry disease

Treatment:–
There’s no cure for Fabry disease, although it may be treated by enzyme replacement.

Until the 2000s, treatment of Fabry disease targeted the symptomatic effects.

In 2001, three Enzyme Replacement Therapies (ERTs) were released: Agalsidase alpha (Replagal, manufactured by Shire) and Agalsidase beta (Fabrazyme, manufactured by Genzyme). These attempt to replace the deficient enzyme by means of infusion, most commonly, every two weeks. The cost of these drugs is problematic (approximately $250,000 US a year/patient) and remains a barrier to many patients in some countries. The infusion may be performed by the patient themselves, in the patient’s home by a registered nurse, or at a medical facility. Enzyme replacement therapy is not a cure, but can allow normal metabolism and both prevent disease progression as well as potentially reverse symptoms.

Pain in Fabry disease responds to ERT, but pain management regimens may also include analgesics, anticonvulsants, and non-steroidal anti-inflammatory drugs.

Prognosis:
Patients with Fabry disease often survive into adulthood but are at increase risk of strokes, heart attack and heart disease, and kidney failure.

Research:
The National Institute of Neurological Disorders and Stroke (NINDS), a component of the National Institutes of Health, conducts and supports research to find ways to treat and prevent lipid storage diseases such as Fabry disease. This research includes clinical studies by the NINDS Developmental and Metabolic Neurology Branch:http://www.ninds.nih.gov/find_people/labs/61.htm.

For more information:

Fabry Support & Information Group
108 NE 2nd Street, Ste. C
P.O. Box 510 Concordia, MO 64020-0510
info@fabry.org

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Tel: 660-463-1355
Fax: 660-463-1356

National Tay-Sachs and Allied Diseases Association
2001 Beacon Street Suite 204
Brighton, MA 02135
info@ntsad.org

National Tay-Sachs & Allied Diseases Association – Home


Tel: 617-277-4463 800-90-NTSAD (906-8723)
Fax: 617-277-0134

National Organization for Rare Disorders (NORD)
P.O. Box 1968 (55 Kenosia Avenue)
Danbury, CT 06813-1968
orphan@rarediseases.org

NORD Rare Diseases – National Organization for Rare Disorders


Tel: 203-744-0100
Voice Mail 800-999-NORD (6673)
Fax: 203-798-2291

Disclaimer: This information is not meant to be a substitute for professional medical advise or help. It is always best to consult with a Physician about serious health concerns. This information is in no way intended to diagnose or prescribe remedies.This is purely for educational purpose.

Resources:
http://www.bbc.co.uk/health/physical_health/conditions/fabrysdisease1.shtml
http://en.wikipedia.org/wiki/Fabry_disease
http://www.medicinenet.com/fabrys_disease/page2.htm
http://www.fabry.org/FSIG.nsf/Pages/Fabry

http://www.fabrazyme.com/patient/disease/fz_us_pt_ds_genetics.asp

http://geneticpeople.com/?p=290

http://medschool.ucsf.edu/lysosomal/fabry/inheritance.aspx

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Categories
Ailmemts & Remedies

Epidermolysis bullosa

Definition:–
Epidermolysis bullosa (ep-ih-dur-MOL-ih-sis buhl-LO-sah) is a group of skin conditions whose hallmark is blistering in response to minor injury, heat, or friction from rubbing or scratching. At least 27 different types of EB have been described, but the three main forms are EB simplex, junctional EB and dystrophic EB. Most are inherited.

Epidermolysis bullosa (EB) is an inherited connective tissue disease causing blisters in the skin and mucosal membranes, with an incidence of 1/50,000. Its severity ranges from mild to lethal. It is caused by a mutation in the keratin or collagen gene.

As a result, the skin is extremely fragile. Minor mechanical friction or trauma will separate the layers of the skin and form blisters. People with this condition have an increased risk of cancers of the skin, and many will eventually be diagnosed with it as a complication of the chronic damage done to the skin.

CLICK TO SEE THE PICTURE

The skin has two layers; the outer layer is called the epidermis and the inner layer the dermis. In normal individuals, there are protein anchors, made of collagen, between the two layers that prevent them from moving independently from one another (shearing). In people born with EB, the two skin layers lack the protein anchors that hold them together, and any action that creates friction between the layers (like rubbing or pressure) will create blisters and painful sores. Sufferers of EB have compared the sores with third-degree burns.

click to see the pictures

The condition was brought to public attention in the UK through the Channel 4 documentary The Boy Whose Skin Fell Off, chronicling the life and death of Jonny Kennedy, an English man with EB.

“Butterfly Children” is a term often used to describe younger patients because the skin is said to be as fragile as a butterfly’s wings.

Children with the condition have also been described as “Cotton Wool Babies,”  and in South America, “Crystal Skin Children” is the term used.

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The inheritance pattern of EB depends on the type. Autosomal dominant variants tend to be milder. Autosomal recessive forms tend to be more severe or even fatal. In these cases there’s usually no family history of the condition.

Around one in 17,000 babies is born with EB. It’s estimated there are around 5,000 people in the UK with this condition. Around one in 227 people carries a gene for EB, although many of these aren’t affected.

EB affects males and females of all races around the world.

Symptoms:–
Symptoms depend on the type of EB and which layer of skin cells is affected.The primary indication of epidermolysis bullosa is the eruption of fluid-filled blisters (bullae) on the skin, most commonly on the hands and feet in response to friction. Blisters of epidermolysis bullosa typically develop in various areas, depending on the type. In mild cases, blisters heal without scarring.

Signs and symptoms of epidermolysis bullosa may include:

*Blistering of your skin — how widespread and severe depends on the type
*Deformity or loss of fingernails and toenails
*Internal blistering, including on the throat, esophagus, upper airway, stomach, intestines and urinary tract
*Skin thickening on palms and soles of the feet (hyperkeratosis)
*Scalp blistering, scarring and hair loss (scarring alopecia)
*Thin-appearing skin (atrophic scarring)
*Tiny white skin bumps or pimples (milia)
*Dental abnormalities, such as tooth decay from poorly formed tooth enamel
*Excessive sweating
*Difficulty swallowing (dysphagia)

Causes:
In most cases, epidermolysis bullosa is inherited. Researchers have identified more than 10 genes involved with skin formation that, if defective, may cause a type of epidermolysis bullosa. It’s also possible to develop epidermolysis bullosa as a result of a random mutation in a gene that occurred during the formation of an egg or sperm cell.

Your skin comprises an outer layer (epidermis) and an underlying layer (dermis). The area where the layers meet is called the basement membrane zone. Where and when blisters develop depends on the type of epidermolysis bullosa.

The three main types of this condition are:

*Epidermolysis bullosa simplex. This most common and generally mildest form usually begins at birth or in early infancy. In epidermolysis bullosa simplex, the faulty genes are those involved in the production of keratin, a fibrous protein in the top layer of skin. The condition causes the skin to split in the epidermis, which produces blisters.

If you have epidermolysis bullosa simplex, it’s likely you inherited a single copy of the defective gene from one of your parents (autosomal dominant inheritance pattern). If one parent has the single faulty gene, there’s a 50 percent chance his or her offspring will have the defect.
Junctional epidermolysis bullosa. This usually severe type of the disorder generally begins at birth. In junctional epidermolysis bullosa, the faulty genes are involved in the formation of thread-like fibers (hemidesmosomes) that attach your epidermis to your basement membrane. This gene defect causes tissue separation and blistering in your basement membrane zone.

*Junctional epidermolysis bullosa is the result of both parents carrying and passing on the defective gene (autosomal recessive inheritance pattern), although neither parent may clinically have the disorder (silent mutation). If both parents have the faulty gene, there’s a 25 percent chance one of their offspring will have the defect and develop the disorder.

*Dystrophic epidermolysis bullosa. This type, whose subtypes range from mild to severe, generally begins at birth or in early childhood. In dystrophic epidermolysis bullosa, the faulty genes are involved in the production of a type of collagen, a protein in the fibers that attach your epidermis to your dermis. As a result, the fibers are either missing or nonfunctional.

Dystrophic epidermolysis bullosa can be either dominant or recessive.

An additional, rare type called epidermolysis bullosa acquisita (EBA) isn’t inherited. Blistering associated with this condition occurs as the result of the immune system mistakenly attacking healthy tissue. It’s similar to a condition called bullous pemphigoid, which also is related to an immune system disorder. EBA has been associated with Crohn’s disease, an inflammatory bowel disease.

Treatment:
There’s no cure for EB. Treatment involves reducing friction and injury, and preventing or treating infection of blisters to reduce chronic damage.

Treatments to reduce scarring and prevent contractures, and to help maintain nutrition when the mouth or oesophagus is affected, are also important.

Antenatal tests are available for EB, at eight to ten weeks of pregnancy.

Recent research has focused on changing the mixture of keratins produced in the skin. There are 54 known keratin genes, 28 type I intermediate filament genes and 26 type II, which work as heterodimers. Many share substantial structural and functional similarity, but are specialized for different cell types or conditions under which they are normally produced. If a drug can shift the balance of production toward an intact keratin gene, symptoms can be reduced. For example, sulforaphane, a compound found in broccoli, was found to reduce blistering in a mouse model to the point where affected pups could not be identified visually, when injected into pregnant mice (5 µmol/day = 0.9 mg) and applied topically to newborns (1 µmol/day = 0.2 mg in jojoba oil).
Lifestyle & Home Remedies:
Careful wound care and good nutrition are essential to your or your child’s health. If blisters are left intact, they can grow, which creates a bigger wound when they finally break. Talk to your doctor about safe ways for you to break and drain blisters before they get too large. Your doctor can also recommend products you can use to keep the affected areas moist to promote healing, such as gauze that contains a moisturizing agent, and prevent infection.

Keep these in mind when tending to your child’s wounds:

*Always wash your hands before touching your child’s blisters.

*If a soiled dressing sticks, don’t pull it off. Soak the area in warm water until the dressing loosens.

If oral or esophageal blisters are inhibiting your child’s ability to eat, here are some suggestions:

*If drinking from breast or bottle causes your infant to develop blisters, try using nipples designed for premature infants or infants with cleft palate or a facial birth defect, or use a syringe or eyedropper.

*For older children, puree foods with extra liquid, such as broth or milk, to make them softer.

*Serve soft, nutritious foods such as vegetable soups and fruit smoothies.

Coping and support:–
Caring for a child with a chronic disease can be stressful. And providing your child with the emotional support needed to live with a chronic illness and to deal with being different from other children can be extremely difficult. For some people, sharing concerns and information with families in similar circumstances can be beneficial.

Ask your health care providers for epidermolysis bullosa support groups in your area. If joining a support group isn’t for you, ask about counselors, clergy or social workers who work with families coping with epidermolysis bullosa.

Prognosis:
Without treatment, these patients are most often going to die from complications caused by epidermolysis bullosa. With treatment, there is a slight chance that the condition could be managed to prolong life, but the treatments are only newly discovered and will take some time to see if they work completely. It is important for those with the disorder to seek treatment when possible to increase the chances of surviving past their teenage years.

Prevention:-

It’s not possible to prevent epidermolysis bullosa, but you can take steps to help prevent blisters, for yourself or for your child.

*Handle your child gently. Your infant or child needs your touch, but be very gentle. To pick up your child, place him or her on soft material, such as cotton, and support under the buttocks and behind the neck. Don’t lift your child from under his or her arms.

*Moderate the temperature in your home. Set your thermostat so that your home remains cool and the temperature remains steady.

*Keep your child’s skin moist. Gently apply lubricants, such as petroleum jelly.

*Dress your child in soft materials. Use clothing that’s simple to get on and off.

*Trim your child’s fingernails regularly. Short fingernails will help prevent scratching.

*Have your child refrain from rough activities. Prevent older children from participating in contact sports or other activities in which skin can be rubbed or injured easily.

*Take care when dressing blisters. Don’t apply adhesive bandages or tape to the skin.

*Avoid hard surfaces and rough materials. Use sheepskin or other soft material on car seats and infant seats. Use a water or air mattress on your child’s bed and soft sheets and blankets.

Disclaimer: This information is not meant to be a substitute for professional medical advise or help. It is always best to consult with a Physician about serious health concerns. This information is in no way intended to diagnose or prescribe remedies.This is purely for educational purpose.

Resources:
http://www.bbc.co.uk/health/physical_health/conditions/epidermolysis1.shtml
http://en.wikipedia.org/wiki/Epidermolysis_bullosa
http://www.mayoclinic.com/health/epidermolysis-bullosa/
http://www.epidermolysisbullosa.net/

http://library.med.utah.edu/kw/derm/pages/ph06_4.htm

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