Stiff skin syndrome

Definition

Stiff skin syndrome (SSS) is a rare syndrome characterized by hard, thick skin, usually on the entire body. The thickening of the skin can limit joint mobility and causes joints to be stuck in a bent position (flexion contractures).

Cause

• Stiff skin syndrome (SSS) is a genetic syndrome caused by changes (mutations) in the FBN1 gene.
• This gene gives the body instructions to make a large protein called fibrillin-1.
• This protein works in the spaces between the cells (the extracellular matrix) to help form elastic fibers which enable the skin, ligaments, and blood vessels to stretch.
• This protein is also important for providing support to bones and the tissues that support the nerves, muscles, and lenses of the eye.

Gene mutations

• Mutations in the FBN1 gene that cause SSS affect the fibrillin-1 protein, which is thought to cause abnormal associations between fibrillin and another protein called elastin.
• When these two proteins interact abnormally in the extracellular matrix, this leads to the development of features of SSS.
• Mutations in the FBN1 gene are also associated with a different genetic syndrome called Marfan syndrome.
• The changes that cause SSS occur in a different part of a gene than the changes that cause Marfan syndrome.
• It is possible that some cases of stiff skin syndrome occur in people without mutations in FBN1.
• More research will be necessary to determine if all cases of stiff skin syndrome are due to mutations in FBN1.

Inheritance

• Stiff skin syndrome (SSS) is inherited in an autosomal dominant manner.
• This means that having a change in only one copy of the FBN1 gene will cause symptoms of stiff skin syndrome.
• We inherit one copy of each of our genes from our mother and the other from our father.
• Some people with stiff skin syndrome have a parent who has the syndrome as well.
• In this case, the affected individual inherited the syndrome from their affected parent.
• In other cases, a person with stiff skin syndrome is the first person in the family to have the syndrome, and neither parent is affected. In these cases, the mutation in FBN1 is new in the affected person, which is called a de novo mutation.

When a person with stiff skin syndrome has children, for each child there is a:

• 50% chance that the child will inherit the mutation in FBN1, which means they will have stiff skin syndrome
• 50% chance that the child will not inherit the mutation in FBN1, which means they will not have stiff skin syndrome.
• Researchers have proposed that, in some cases, people with stiff skin syndrome may only have a mutation in FBN1 in some cells of the body. This could cause a less severe form of stiff skin syndrome that is called segmental stiff skin syndrome because it only affects certain parts of the body.

Onset

The onset of signs and symptoms can range from presenting at birth through childhood.

Signs and symptoms

• The signs and symptoms associated with stiff skin syndrome (SSS) include hard, thickened skin, especially affecting the buttocks, thighs, and shoulders. Other symptoms may include excessive hair growth (hypertrichosis), loss of body fat (lipodystrophy), scoliosis, muscle weakness, slow growth, and short stature.
• Some people with SSS may have restrictive pulmonary changes and a narrow chest cavity that cause trouble breathing.
• Many individuals with SSS walk on their tiptoes.
• The thickening of the skin associated with stiff skin syndrome can result in difficulty moving joints, as they become stuck in the bent position (flexion contractures).
• This typically affects the larger joints, such as the shoulders, elbows, and knees.
• The ability to flex the joints of the fingers may also be affected, as individuals with this syndrome may develop nodules on the skin of the fingers.
• SSS is a slowly progressive syndrome, meaning that the signs and symptoms worsen as individuals get older.

Clinical presentation

For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed.

80%-99% of people have these symptoms

• Lack of skin elasticity
• Limitation of joint mobility(Decreased joint mobility)
• Thickened skin(Thick skin)

5%-29% of people have these symptoms

• Abnormal circulating lipid concentration
• Aplasia/Hypoplasia of the skin(Absent/small skin)
• Glaucoma
• Hypertension
• Impaired pain sensation(Decreased pain sensation)
• Lipoatrophy(Loss of fat tissue in localized area)
• Lipodystrophy(Inability to make and keep healthy fat tissue)
• Midface retrusion(Decreased size of midface)
• Muscle weakness(Muscular weakness)
• Nephrolithiasis(Kidney stones)
• Peripheral neuropathy
• Retinal detachment(Detached retina)
• Sensorineural hearing impairment
• Short stature(Decreased body height)
• Strabismus(Cross-eyed)
• Subcutaneous nodule(Firm lump under the skin)
• Type II diabetes mellitus(Noninsulin-dependent diabetes)

Diagnosis

• A diagnosis of stiff skin syndrome (SSS) can be made based on a clinical evaluation that is consistent with the signs and symptoms of the syndrome.
• A healthcare provider may observe that a child has features of stiff skin syndrome.
• In some cases, biopsies of the skin can be used to determine if the skin has certain characteristics when viewed under a microscope.
• In some cases, genetic testing of the FBN1 gene may be used to confirm the diagnosis.

Treatment

• At this time, no specific therapies are available to reverse the symptoms of stiff skin syndrome (SSS).
• The recommended therapies aim to address issues moving the joints that may develop as a symptom of SSS.
• Regular physical therapy and exercise may be recommended to improve or maintain joint movement.
• A number of treatments have been tried in individual cases, including steroids, immunosuppressant drugs, psoralens (light-sensitizing medications), and light therapy.
• These treatments have not been helpful in slowing or stopping symptoms of SSS.