CUTIS LAXA INTERNATIONALE
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What is Cutis Laxa ?
The sole purpose of this page is to allow patients and their families to know a little more about Cutis Laxa. It is definitely not exhaustive.
like N.O.R.D. http://www.rarediseases.org
http://www.dermatlas.comor Gale Encyclopedia of Medecine, author : Lorraine Lica, Gale Research 1999 http://www.findarticles.com as well as other medical or scientific sites give a definition or a description of Cutis Laxa.
have chosen this one because of its clarity, and the most recent informations it contains.
Since that in 2002 researchers started working on Cutis Laxa 12 gene mutations have been identified:
ě Elastine (ELN) (2 mutations) - ADCL
ě Fibuline5 (FBLN5) - ARCL1A
ě Fibuline4 (FBLN4) - ARCL1B
ě LTBP4 - ARCL1C
ě ATP6V0A2 - ARCL2A
ě PYCR1 - ARCL2B
ě ATP6V1E1 ou ATP6V1A - ARCL2C
ě ALDH18A1 - ARCL3 (De Barsy Syndrom)
ě SCYL1BP1 (GÚroderma Osteodysplastica)
ě ATP7A (Occipital Horn Syndrom)
ě RIN2 (MACS Syndrom)
Cutis laxa (CL) is inherited in many different ways, depending on the type of cutis laxa. There are autosomal dominant (AD), autosomal recessive (AR), and X-linked recessive (XLR) forms of inherited cutis laxa. Cutis laxa can also be acquired by an individual who does not have one of the inherited forms of CL. The cause of the acquired form of CL is unknown, but it typically affects older adults following a severe illness with fever and rash. These individuals may have incurred damage to their connective tissue from some environmental cause such as exposure to certain medications, infections, cancer treatments, or secondary to an autoimmune disease such as Lupus or Rheumatoid Arthritis. For more information visit our Genetic transmission page.
Dominant Cutis Laxa (ADCL)
ADCL symptoms begin anytime between birth and young adulthood. Symptoms include only cutis laxa in some of these patients. However, some families also exhibit specific facial features mainly involving the nose and ears, and cardiovascular and pulmonary problems such as aortic aneurysm and emphysema. Echocardiography and pulmonary function testing is recommended for these patients in order to identify heart and lung complications before they become life-threatening. Although most cases of ADCL result from mutations in the elastin (ELN) gene, at least one family with ADCL has been found to have a mutation in the Fibulin-5 (FBLN5) gene, which is the cause of autosomal recessive cutis laxa type 1B (ARCL1B).
Autosomal Recessive Cutis Laxa (ARCL)
ARCL is divided into several subtypes, based both on specific symptoms and the gene which causes the condition. ARCL is divided into ARCL1, ARCL2, and ARCL3, which are then further divided into additional subtypes.
ARCL1A or FBLN5-Related Cutis Laxa is characterized by cutis laxa, hernias, and pulmonary involvement such as emphysema from a young age. However, there is a high degree of variability in onset age for these symptoms, even within the same family. ARCL1A is caused by mutations in the FBLN5 gene.
ARCL1B or FBLN4 (EFEMP2)-related cutis laxa is characterized by cutis laxa and the involvement of other body symptoms, namely the cardiovascular system (arterial problems such as tortuosity, aneurysms and stenosis), skeletal system (loose joints, long thin fingers, hernias, and bone fragility), and some distinctive features involving the face and head (small chin, high-arched palate, and widely spaced eyes). ARCL1B can be extremely severe resulting in death soon after birth, or it can be limited to only the blood vessel and facial features noted above. ARCL1B is caused by mutations in the FBLN4 (EFEMP2) gene.
ARCL1C or LTBP4-Related Cutis Laxa is characterized by cutis laxa, as well as severe pulmonary, gastrointestinal, and urinary problems. ARCL1C is also known as Urban-Rifkin-Davis Syndrome (URDS). ARCL1C is caused by mutations in the LTBP4 gene.
ARCL2A or ATP6V0A2-related cutis laxa is caused by mutations in the ATP6V0A2 gene. Individuals with this type of cutis laxa have wrinkly skin over the entire body, which typically improves with age. Other features in these children include an enlarged anterior fontanel, dislocation of the hips that is present at birth, hernias, and nearsightedness. Many individuals with this condition have severe developmental delay and seizures. Wrinkly Skin Syndrome, which causes wrinkled skin, small head size, and mental retardation, as well as muscle and skeletal problems, is caused by mutations in the same ATP6V0A2 gene.
ARCL2B or PYCR1-related cutis laxa is caused by mutations in the PYCR1 gene. Clinical features of this disease include cutis laxa leading to an aged appearance, growth delay, developmental delay, joint and skeletal problems, small head size, large forehead, triangular-shaped face, and large ears.
ARCL3 or De Barsy syndrome has phenotypic overlap with ARCL2A and ARCL2B. It causes cutis laxa with growth retardation, moderate to severe mental retardation, cataracts, and loose joints. Other skin problems in addition to the cutis laxa contribute to an aged appearance. There are typically neither cardiovascular nor pulmonary symptoms. Some patients initially diagnosed with De Barsy syndrome were later found to have mutations in PYCR1 (ARCL2B), ATP6V0A2 (ARCL2A), or ALDH18A1.
Occipital Horn Syndrome (OHS)
is rare, with fewer than 100 cases reported worldwide. Symptoms usually begin
within the first decade of life, and include cutis laxa, skeletal problems (bony
growths on the back of the skull, loose joints, and short stature), and
pulmonary (lung), cardiovascular (heart), and gastrointestinal problems such as
emphysema, aneurysms, and hernias. There can also be muscle weakness, and
intelligence ranges from low normal to mild mental retardation. OHS is a
disorder of copper metabolism caused by mutations (changes) in the
gene. Mutations in this gene prevent the body's cells from obtaining enough
copper, which is necessary for the proper function of enzymes within many cell
types, including bone, skin, and hair, as well as cells that comprise blood
vessels and the nervous system. OHS is considered a less severe form of
which is also caused by mutations in the ATP7A gene. OHS has previously
been referred to as Ehlers-Danlos Syndrome Type IX and X-linked Cutis Laxa. It
has been called X-linked Cutis Laxa because the ATP7A gene is located on the X
chromosome and inherited as an X-linked recessive (XLR) disease. For this
reason, OHS typically affects only males.
Gerodermia Osteodysplastica (GO)
is a type of cutis laxa that occurs in babies or young children. These children
have loose skin, mostly on the hands, feet, and stomach, as well as their face.
Other features include a small jaw, hip dislocations, hernias, osteoporosis,
fractures, and dwarfism. As with ARCL3, there are typically neither
cardiovascular nor pulmonary symptoms. GO is also an autosomal recessive
condition caused by mutations in the
GORAB (SCYL1BP1) gene.
is macrocephaly (large head), alopecia (sparse hair), cutis laxa, and scoliosis.
Other features include puffy eyelids, flat feet, loose joints, and short
stature. MACS is an autosomal recessive disorder caused by mutations in the
Acquired Cutis Laxa
Acquired cutis laxa typically occurs in older adults. Although its cause is unknown, it has been observed in some individuals after certain environmental exposures, such as some medications, infections, or autoimmune diseases. Acquired cutis laxa is not inherited. However, one aspect of Dr. Urban's research is to determine whether some individuals may have a genetic susceptibility to developing cutis laxa after certain exposures.
Diagnosis of cutis laxa is typically made by physical examination of the skin by a physician such as a geneticist or dermatologist. The specific type of cutis laxa is determined by the associated features, family history information, and in some cases can be confirmed by genetic testing. However, some patients with or without a clinically identified cutis laxa gene mutation may choose to enroll in Dr. Urban's cutis laxa research study at the University of Pittsburgh.
After initial diagnosis, patients with cutis laxa typically receive cardiovascular and pulmonary evaluations, such as echocardiograms and lung function testing. Management of individuals with cutis laxa includes treatment of symptoms, such as surgical repair of hernias, medications such as beta-blockers may be considered to prevent growth of aortic aneurysms, and pulmonary emphysema is treated symptomatically. Regular cardiovascular and pulmonary follow-up should begin at birth or immediately after diagnosis. Environmental triggers such as cigarette smoking, which can worsen emphysema, and sun bathing, which can damage the skin, should be avoided, especially by patients with cutis laxa. Some individuals with cutis laxa may choose to undergo plastic surgery. Although the results from plastic surgery are typically very good, they may not be permanent, as the loose skin may reoccur.
The prognosis for Cutis Laxa varies with the form of the disorder. The effects may be relatively mild with individuals living a fairly normal, full life, or the disease may be fatal.
The inherited forms of cutis laxa are genetically determined and are not currently preventable. Genetic counseling can be helpful for anyone with a family history of cutis laxa. The cause of acquired Cutis Laxa is not known, so no preventive measures can be taken.
Autosomal : Refers to the 22 pairs (in human) of chromosomes not involved with sex determination
Connective tissue : Tissue that supports and binds other tissue, much of it occurs outside of cells (extra-cellular) and consists of fibrous webs of the polymers, elastin and collagen. Cutis Laxa is associated with defects in these fibers.
Diverticula : Pouches in the walls of organs.
Dominant trait : A genetic trait where one copy of the gene is sufficient to yield an outward display of the trait, dominant gene mask the presence of recessive gene, dominant trait can de inherited from only one parent.
Duodenum : The uppermost part of the smal intestine, about 10 in. long.
Esophagus : The tube connecting the throat to the stomach, about 10 in. long.
Gene : A
portion of the DNA molecule that either codes for a protein or RNA molecule or
has a regulatory function.
Recessive trait : An inherited trait that is outward obvious only when two copies of the gene for the trait are present, an individual displaying a recessive trait must have inherited one copy of the defective gene from each parent.
Sex-Linked : Refers to genes or traits carried on one of the sex chromosomes, usually the X.
Tortuous arteries : Arteries with many bends and twists.
X Chromosome : One of the two types of sex chromosomes ; females have two X chromosomes, while males have one X chromosome and one Y chromosome.