COL5A1 Gene ... Official name

Let’s start with classic types of Ehlers-Danlos syndrome (EDS).

For ‘Classic type’ of EDS two genes are responsible — COL5A1 & COL5A2.

COL5A1 Gene

Official Name        :      Collagen, type V, alpha 1

Official Symbol      :      COL5A1 

Molecular Bases of EDS ... (2)

As we already know that mutations in COL1A1, COL1A2, COL3A1, COL5A1, COL5A2, ADAMTS2, PLOD1 and TNXB gene cause Ehlers-Danlos syndrome — some of these genes (COL1A1, COL1A2, COL3A1, COL5A1 & COL5A2) provide instructions for making proteins that are used to assemble different types of collagen. ADAMTS2, PLOD1 & TNXB provide instructions for making proteins that process or interact with collagen. Now ‘Collagens’ are molecules that give structure and strength to connective tissues throughout the body.

Mutations that cause the different forms of Ehlers-Danlos syndrome disrupt the structure, production, or processing of collagen, preventing these molecules from being assembled properly. These defects weaken connective tissues in the skin, bones and other parts of the body causing EDS.

Molecular Bases of EDS ... (1)

The progress of the Human Genome Project and other advances in molecular genetics has provided much information regarding the molecular basis of Ehlers-Danlos syndrome. Physical positions of respective genes and their locations on chromosomal maps are as follows:

Molecular Bases of EDS

Type	Protein Abnormality	Gene Abnormality	Chromosome Locus
Classic	Type V collagen	COL5A1 COL5A2	9q34.2-34.3 2q31
Hypermobility	Unknown	Unknown	Unknown
Vascular	Type III collagen	COL3A1	2q31
Kyphoscoliosis	Lysyl hydroxylase deficiency	PLOD1	1p36.3-36.2
Arthrochalasia	Type I collagen	COL1A1 COL1A2	17q31-22.5 7q22.1
Dermatosparaxis	N-proteinase	ADAMST2	5q23-24

Treatments & Drugs

There is no cure for Ehlers-Danlos syndrome, but treatment can help to manage the symptoms and prevent further complications.

Medications

Health providers/doctors may prescribe drugs to control:

 @   Pain: If over-the-counter pain relievers — such as ibuprofen (Advil, Motrin IB, others) and naproxen (Aleve) — aren't enough, doctor may prescribe stronger medications for joint or muscle pain.

 @   Blood pressure: As blood vessels are more fragile in some types (e.g. Vascular type) of Ehlers-Danlos syndrome, doctor may want to reduce the stress on the vessels by keeping the blood pressure low.

Physical Therapy

Joints with weak connective tissue are more likely to dislocate. Exercises to strengthen the muscles around a joint can help stabilize the joint. Physical therapist might also recommend specific braces to help prevent joint dislocations.

Surgical & Other Procedures

In rare cases, surgery is recommended to repair joints damaged by repeated dislocations. However, the skin and the connective tissue of the affected joint may not heal properly after the surgery.

Source: www.mayoclinic.com

Contraindications / Precautions for Treatment ...

Contraindications:

Any activity that would put stress on locked joints or the heart such as weight lifting, strength testing, carrying heavy weight, playing any wind instruments (requiring forced air) as well as pushing or pulling. 

Precautions:

@ Avoid skin irritation from treatment modalities

@ Minimize stress on painful and lax joints

@ Minimize activities that would be injury producing (i.e. contact sports)

@ Avoid drugs which would affect coagulation (vascular issues)

@ Surgical sutures removal should be delayed due to skin fragility and impaired healing 

Source: www.brighamandwomens.org

Indications for Treatment ...

Treatment is aimed at addressing all the areas of impairment. Because of the various types and the variety of presentations, a wide range of professionals is necessary to care for this population. The indications for occupational therapy are as follow: 

@ Fragile skin, easy bruising

@ Joint hypermobility and excessive dislocations

@ Poor tissue healing, wide and atrophic scars

@ Chronic joint pain

@ Osteopenia and postural changes

@ Impaired function or performance of activities of daily living (ADLs)

@ Decreased knowledge of condition and its impact on function

But You Don't Look Sick ..... A Patient's Experience

The Villefranche Classification of EDS

Type	Inheritance	Previous Nomenclature
Hypermobility	Autosomal Dominant	Type III
Classic	Autosomal Dominant	Types I & II
Vascular	Autosomal Dominant	Type IV
Kyphoscoliosis	Autosomal Recessive	Type VI (Lysyl hydroxylase deficiency)
Arthrochalasia	Autosomal Dominant	Type VII A&B
Dermatosparaxis	Autosomal Recessive	Type VII C

Genetic Influence...

Genetic link is the major risk factors for Ehlers-Danlos Syndrome (EDS). The various types of EDS are either Autosomal Dominant (AD) or Autosomal Recessive (AR) or X-Linked Recessive (X-LR).

As I already discuss in my earlier post that genes can be ‘dominant’ or ‘recessive’ ~ Dominant genes show their effect even if there is only one copy of the gene in the pair and for a person to have a recessive disease or characteristic, the person must have the gene on both chromosomes of the pair.

Affected first-degree relatives are identified in as many as 50% of cases. An autosomal dominant pattern of inheritance is most common, although autosomal recessive and X-linked transmission also have been documented. 

Clinical Presentation of Various Types of EDS

We already discuss that earlier experts divided Ehlers-Danlos Syndrome (EDS) into 11 subtypes — I through XI. To simplify these classifications scientists recognized the subtypes according to signs and symptoms and arranged them into six different types:

Hypermobility type (formerly type III)

This is the most common form of EDS. It may affect as many as one in 10,000 - 15,000 people. Signs and symptoms include:

E Loose, unstable joints

E Chronic joint pain

Classical type (formerly types I and II)

This type probably affects less than 1 in 20,000 - 40,000 people. Signs and symptoms include:

E Highly elastic, velvety skin

E Fragile skin that bruises/tears easily

E Slow and poor wound healing leading to scarring

E Noncancerous fibrous growths on pressure areas, such as elbows and knees; fatty growths on the shins and forearms

E Loose joints prone to dislocation and may delay the development of large-motor skills

 Vascular type (formerly type IV)

This is one of the most serious forms of EDS. It affects an estimated 1 in 100,000 - 200,000 people. Signs and symptoms include:

E Fragile blood vessels and organs that are prone to rupture

E Thin, fragile skin that bruises easily

E Veins visible beneath the skin

E Distinctive facial features, including protruding eyes, thin nose and lips, sunken cheeks and small chin

E Loose joints usually limited to the fingers and toes

  

Kyphoscoliosis type (formerly type VI)

This is another uncommon form of EDS. Fewer than 60 cases have been reported worldwide. Signs and symptoms include:

E Progressive curvature of the spine (scoliosis)

E Fragile eyes that are easily damaged

E Severe, progressive muscle weakness

Arthrochalasia type (formerly known types VII A and B)

Arthrochalasia is also very rare. Worldwide only about 30 cases have been reported with the followings signs and symptoms:

E Very loose joints and dislocations involving both hips, which may delay the development of large-motor skills

E Stretchy, fragile skin prone to bruising

E Early-onset arthritis

E Increased risk of bone loss and fracture

Dermatosparaxis type (formerly called type VIIC)

This form is also very rare. Only about 10 cases have been reported worldwide. Signs and symptoms include:

E Extremely fragile and sagging skin

E Loose joints, which may delay development of large-motor skills in children. 

Other types

The remaining subtypes ~ types V, VIII, IX, X, and XI ~ are classified as “other”. These are rare, and some are not well-defined. Some characteristics of these types:

E Type V has characteristically fragile skin, although bruising and loose joints are uncommon. 

E Type VIII involves teeth and gums as well as skin and joints (periodontal form).

E Type IX may cause chronic diarrhea and light headedness due to low blood pressure in addition to other signs and symptoms.

E Types X and XI are characterized by loose joints and are very similar and have sometimes been considered one type rather than two.

E Type X may lead to problems with blood clotting. 

Source: www.brighamandwomens.org