Werner Syndrome

By admin On Apr 17, 2023

Ovid: Oncology and Basic Science

Editors: Tornetta, Paul; Einhorn, Thomas A.; Damron, Timothy A.

Title: Oncology and Basic Science, 7th Edition

> Table of Contents > Section
II – Specific Bone Neoplasms and Simulators > 7 – Congenital and
Inherited Bone Conditions > 7.6 – Werner Syndrome

7.6

Werner Syndrome

Kathryn Palomino

Werner syndrome is a rare hereditary systemic disease,
also known as adult progeria. It is characterized by signs of premature
aging (gray hair, skin changes, and cataracts) in patients after the
onset of puberty. Atherosclerosis, diabetes, and neoplastic diseases
are also associated with the syndrome. Life expectancy is around 50
years, with cardiovascular, atherosclerotic disease and cancers being
the most common causes of death.

Etiology

Werner syndrome gene (WRN) is located on chromosome 8 (8p11-12).
WRN protein encodes DNA helicase and exonuclease activities and is involved in response to DNA damage.
Inheritance: autosomal recessive

Epidemiology

Prevalence: ranges from 1/22,000 to 1/10⁶
More common in Japanese and Caucasian populations but has been described throughout the world
Frequency is higher in populations with consanguineous marriage.
Male:female equal
Age: diagnosis is usually not made until adulthood

Pathophysiology

Precise mechanism for the phenotype of Werner syndrome is unknown.
- Defective DNA metabolism is involved, leading to altered bioavailability of growth factors.
RecQ helicase deficiency syndrome leads to heritable cancer predisposition (10% to 30% increased risk).
- Numerous types of tumors are seen (Fig. 7.6-1).

Diagnosis

Nonorthopaedic Clinical Features

Develop at onset of puberty
Dermatologic changes resembling scleroderma
Short stature (mean height: male 157 cm; female 147 cm)
Premature graying and alopecia
Nonsenile cataracts
Weak, high-pitched voice
Calcific deposits on heart valves
Atherosclerosis
Diabetes mellitus
Hypogonadism
Neoplasm (nonorthopaedic)
- Thyroid carcinomas
- Melanoma
- Meningioma
- Hematological disorders

Figure 7.6-1 Tumors associated with Wermer syndrome.

Orthopaedic Clinical Features

Osteoporosis, usually presenting with vertebral abnormalities or insufficiency fractures
Muscle wasting
Calcific deposits in ligaments and tendons
Pes planus
Neoplasms (orthopaedic)
- Soft tissue sarcomas: most common malignancy
- Osteosarcoma

Diagnostic Algorithm

Presence of all consistent clinical features with at least two of the following:
- Loss of WRN protein from peripheral lymphocytes or fibroblasts
- Elevated 24-hour urinary hyaluronic acid level
- Detection of mutation of WRN gene on chromosome 8 by Western blot

Treatment

There is no specific therapy for Werner syndrome.
Management involves symptomatic medical management of conditions as they arise.
Management of orthopaedic conditions
- Osteoporosis: human insulin-like growth factor has been used
- Fractures: heal poorly regardless of method of treatment
- Pes planus: best managed with orthotics
- Surgical incisions heal poorly.
Tumor management
- Early diagnosis of Werner syndrome and
  subsequent hypervigilance in investigating skin of soft tissue
  abnormalities or bone pain are paramount in decreasing death rate from
  malignancy in the Werner syndrome patient.
- Unique features of malignancy in Werner syndrome patients
  - Develop at early age
  - Develop in unusual sites
  - May develop multiple primaries (synchronously or metachronously)
  - One of most common causes of death