Warner Syndrome - Clinical Features, Health Conditions, Cause, Diagnosis, and Treatment

Introduction:

Warner syndrome is a rare autosomal recessive disorder, in which each parent carries a gene mutation that is passed down to the offspring but parents are not affected by the condition. It is also called adult premature aging syndrome or adult progeria. Werner syndrome has a characteristic feature of premature appearance, graying, and loss of hair associated with normal aging and cancer predisposition. Individuals with this syndrome have normal development until the age of ten and symptoms start to appear as a teenager. Affected individuals do not have a growth spurt (a short phase where the child has quick physical growth in weight and height). Individuals with Warner syndrome live until 40 to 50 years of age and have complications due to atherosclerosis (hardening of blood vessels) and cancers.

What Is Warner Syndrome?

Warner syndrome is a rare inherited disorder that is characterized by rapid aging which starts in early adolescence or young adulthood which is from 12 to 21 years of age and is associated with an increased risk of cancer such as skin cancer, thyroid cancer, and sarcoma (a type of cancer which starts in the bone and soft tissue such as fat, cartilage, muscle, fibrous tissue, blood vessels, and connective tissues). They have clinical features such as short height, thinning, unusual facial features, and voice change. This can also cause health problems such as skin ulcers, cataracts (opaque area in the lens), diabetes (a metabolic disorder that causes an increase in blood sugar levels), fertility problems, hardening of the arteries, and osteoporosis (a bone disease in which its density and weight decrease). This occurs due to a mutation in the WRN gene.

What Are the Clinical Features of Warner Syndrome?

The clinical features of Warner syndrome include:

• Short stature.

• Prematurely aged appearance.

• Thin arms and legs.

• Thick neck due to abnormal deposition of fat.

• Thin hardened skin.

• Hyperkeratosis (thick skin).

• Voice changes (hoarse voice).

• Unusual facial features are described as bird-like.

• Sparse scalp hair.

• Graying hair.

• Pili torti (increased fragility of hair).

• Abnormal hair whorl (a patch of hair that grows in the opposite direction compared to the rest of the hair).

• White forelock (a depigmented area of white hairs in a triangular shape that is present in the front midline portion of the scalp).

• Abnormal chest wall.

• Convex nasal ridge (anterior curving of the nasal ridge).

• Rocker bottom foot (anomaly of the foot, where it flexes in opposite direction).

What Are the Health Conditions That Occur Due to Warner Syndrome?

The health conditions that occur due to Warner syndrome are:

• Cataracts (opaque or cloudy area in the lens).

• Abnormal retinal pigmentation.

• Aplasia (absent) or hypoplasia (underdeveloped) of the skin.

• Lipoatrophy (loss of fat tissue around a particular area).

• Type 2 diabetes (a metabolic disorder that increases the blood sugar levels which occurs due to a decrease in insulin production or resistance to insulin by the body).

• Atherosclerosis (occurs due to the build-up of plaque in the blood vessels and making it hard).

• Osteoporosis (a bone disorder that causes decreased bone density and bone mass).

• Chondrocalcinosis (a type of arthritis in which there is a deposition of calcium pyrophosphate crystals).

• Cancers such as skin cancer, thyroid cancer, lung, oral cavity, and sarcoma (cancer of soft tissues and bone).

• Congestive heart failure.

• Myocardial infarction (also called a heart attack where there is a complete stoppage of blood flow to a part of the heart).

• Hypogonadism (decreased function of reproductive organs).

• Abnormal morphology of testis.

• Absent or underdeveloped testes.

What Is the Cause of Warner Syndrome?

Warner syndrome occurs due to a mutation in the WRN, which is inherited in an autosomal recessive pattern, where both parents carry one copy of the mutated gene each and are passed down to offspring, but parents are not affected by this condition. The features of the WRN gene are:

• The WRN gene is located on chromosome 8.

• WRN genes provide instruction in the formation of a protein called Warner protein, which plays a role in repairing damaged DNA.

• Warner protein also functions as an enzyme called helicase. Helicase enzymes play a role in separating and unwinding the double-stranded DNA.

• Warner protein also functions as an enzyme called exonuclease. Exonuclease enzyme plays a role in trimming the damaged ends of DNA by removing the nucleotide bases.

• Warner protein also plays a role in replicating DNA that occurs before cell division and also helps in transcription by transferring information present in genes to the cells in the formation of proteins.

• Warner protein also maintains DNA at telomeres (ends of DNA).

• Therefore, Warner protein first unwinds the double-stranded DNA and then repairs the damaged part, thereby maintaining the structure and integrity of DNA.

Mutations in the WRN gene lead to the formation of abnormal non-functioning short Warner protein which can break down more rapidly and does not get transported to the nucleus. Cells that contain Warner protein stop dividing early thereby, affecting growth and also causing the accumulation of damaged DNA and giving rise to multiple health problems.

What Is the Diagnosis of Warner Syndrome?

The diagnosis of Warner syndrome includes:

• The diagnosis is made in the teenage years based on physical characteristics like premature aging.

• Genetic testing can be done which shows a mutation in the WRN gene.

• A family history is also considered as it is an autosomal recessive inherited disorder.

• A preimplantation genetic diagnosis can be carried out before in vitro fertilization (IVF), which can be helpful in early diagnosis.

What Is the Treatment of Warner Syndrome?

There is no treatment or cure for Warner syndrome. Management includes relieving the symptoms and treating complications. Treatment includes multiple healthcare specialty teams such as endocrinologists, to treat type 2 diabetes, ophthalmologist to treat eye abnormalities such as cataracts and abnormal retinal pigmentation, oncologist to treat cancers, and a genetic counselor to educate the individuals about Warner syndrome.

Conclusion:

Warner syndrome is a rare inherited disorder with typical features of premature aging associated with health problems and cancers. Individuals with this syndrome live from 40 to 50 years of age. There is no specific cure for this syndrome and treatment includes managing to relieve the symptoms and prevent complications.