Rothmund-Thomson Syndrome

By admin Last updated Oct 19, 2024

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 > 7.5 – Rothmund-Thomson Syndrome

7.5

Rothmund-Thomson Syndrome

Kathryn Palomino

Rothmund-Thomson syndrome is an autosomal recessive congenital syndrome (Box 7.5-1)
associated with potential development of osteosarcoma. Since the
patient usually arrives in the orthopaedic surgeon’s office with the
diagnosis, the key for the orthopaedic surgeon is simply to recall the
risk of development of osteosarcoma and to evaluate all musculoskeletal
complaints in that context.

Pathogenesis

Etiology

Genetic defect: subset associated with defect in RECQL4 helicase gene at locus 8q24
Inheritance: autosomal recessive (AR)

Epidemiology

Rare
- Incidence unknown
Male:female 2:1

Pathophysiology

Known genetic defect (RECQL4) present in 40% of cases
- Normal expression highest in thymus and testes
- Homology with genes that cause syndromes with some clinical overlap
  - Bloom syndrome: BLM gene defect on 15q26 with AR inheritance and increased incidence of osteosarcomas
  - Werner syndrome: WRN gene defect on 8p11-12 with AR inheritance and increased risk of various bone and soft tissue tumors

Diagnosis

Although no specific criteria have been established,
generally the diagnosis is first suspected in the neonate based upon
the characteristic rash that occurs within the first 6 months of life.
Genetic testing may identify the characteristic defect in up to 40% of
cases. Similar disorders, such as Werner syndrome, should be excluded
(e.g., urinary testing for the characteristically elevated hyaluronic
acid in Werner syndrome).

History and Physical Examination

Physical examination reveals the key finding in
Rothmund-Thomson syndrome, the sun-sensitive erythematous facial rash
that spreads to buttocks and extremities and eventually leaves a
characteristic mixed hyper- and hypopigmented rash (poikiloderma) for
which the syndrome received its other name, poikiloderma congenitale.
Other nonorthopedic and orthopaedic manifestations may be present.

Nonorthopaedic clinical features
- Poikilodermatous skin changes
  - Develop in first 6 months of life
  - Usually appear in sun-exposed areas and around buttocks (Fig. 7.5-1)
  - Photosensitivity and blister formation
- Thin hair and/or alopecia
- Short stature
- Juvenile cataracts
- Malignancies, particularly of the skin
Orthopaedic clinical features
- Osteoporosis
  
  Figure 7.5-1 Rothmund-Thomson syndrome: posterior leg poikiloderma. (Image provided by Stedman’s.)
- Clavicular hypoplasia
- Syndactyly
- Patella aplasia
- Genu valgum
- Benign osseous defects
  - Osteosclerosis
  - Bone cysts
  - Metaphyseal chondrodysplasia
- Sarcomas
  - Second most frequently occurring malignancy

Differential Diagnosis

Werner syndrome
Bloom syndrome

Treatment

No specific treatment for Rothmund-Thomson syndrome exists.
Symptomatic management of conditions as they arise
Surgical treatment not advised for height, alignment, or nonmalignant osseous abnormalities due to poor bone and wound healing
Hypervigilance in investigating bone pain
and or soft tissue swelling is mandatory due to increased risk of
malignancy, including multiple primary malignancies.