Dermatologic (and other) Manifestations ofRothmund-Thomson Syndrome
October 10, 2020
Moise L. Levy, M.D.
Dell Children’s Medical Center
Dell Medical School, University of Texas
Austin, TX

Case History⚫3 month old girl with fine hair, lashes, browsand missing thumbs⚫Seen again at 13 yrs⚫Again with same findings; in addition wasfound to have differences in skinpigmentation, absent carpal bones, decreasedbone density, palmoplantar hyperkeratoses,
RECQL4 mutations

Case History

Case Rep Dermatol 2014;6:176

Rothmund-Thomson Syndrome⚫AR⚫Poikiloderma⚫Cataracts⚫Short stature⚫Limb defects⚫Malignancy

RTS Erythema within 1st six months-90% in first year of life
-Face, extremities, buttocks
 Photosensitivity???; Inconsistent data
regarding sensitivity to UV/IR Heat intolerance
 Swelling

Br J Dermatol 2011;164:245
GeneReviews 2016

RTS
 Blistering Poikiloderma (atrophy [thinning],dyspigmentation, telangiectasia[fine superficialvessels]) develops later;-can be in adulthood (?)
 Hyperkeratoses [thickening of skin]; ~ 30% asearly as 2 yrs

Rothmund-Thompson Syndrome Ectodermal defects/differences-Skin, Nails-Hair-Teeth Eyes Gastrointestinal
 Malignancies; bone, skin, others
 ? Link to aging and cancer susceptibility (RECQ/RECQL)Rothmund-Thomson Syndrome andAgingAgeing Res Rev 2017

Rothmund-Thomson Syndrome
Differential Diagnosis
 Baller-Gerold syndrome; craniosynostosis
 Clericuzio poikiloderma; neutropenia, infections
 Bloom’s (telangiectasia) and Werner’s Hereditary sclerosing poikiloderma; withsclerodermatous plaques on palms/soles
 Kindler syndrome; bullous disease Progressive reticulated telangiectatic erythema Others

Baller-Gerold Syndrome-Craniosynostosis w/radial defects-AR-Short stature-CHD, GU abnl-MR

RECQL Syndromes
Rothmund-Thomson• Poikiloderma, Sparse hair, Short stature, Long bone differences• Palmoplantar keratoderma, Osteosarcoma, Skin CA

Bloom Syndrome• Microcephaly, Immunodeficiency, Malignancies (leukemia, lymphoma)• Poikiloderma, Telangiectasia central face/neck (“butterfly” distribution), Café aulait

Werner Syndrome• Graying of hair, Short stature,Sclerodermatous skin changes (firm areas)• Ulcers on feet, ankles• Malignancies

Rothmund-Thomson
Poikiloderma

Hyper-/Hypopigmentation
Telangiectasia (fine, discrete,small vessels)
Atrophy (thinning)

Skin Hyperpigmentation

RTS

Rothmund-Thompson/Hair⚫ Fine, thinned⚫ Brows, lashes 1st⚫ Alopecia; partial or total⚫ One report of pili annulati (a diff.
of hair shaft appearance under
microscope; may be spangled; maybe prone to breakage
JEADV 2108;32:e208

Rothmund-Thompson/Nails⚫Dystrophic (different growth)-30%-Thinned

RTS - Hyperkeratosis

Often painful! Occur in ≅ 30%
With nail changes, speaks to difference in keratin function…
- (possible therapeutic options)RTS – Granulomatous Lesions⚫ Have been reported previously in patients withimmunodeficiency states⚫ Thickened areas of skingrowths⚫ SOME reports ofimmunodeficiency(RARE) in RTS
Orphanet J Rare Dis 2010;5:37

Rothmund Thomson Syndrome
Dental⚫Caries; pulp involvement by radiography*⚫Congenital anodontia*⚫Microdontia⚫Overall incidence of dental/RTS:- 27%-59%
BMJ Case Rep 2015;doi:10.1136/bcr-2015-209994

Rothmund-Thomson Syndrome

Rothmund-Thomson Syndromeand Mouse Model Findings

Note: Poikiloderma not seen in this mouse modelNot all RTS cells are Xray/UV sensitive
Hum Mol Genet 2003

RTS and Malignancies

Other malignancies rarely reported
Am J Med Genet Part A 2010;152A:1575

Rothmund-Thompson
Skin Malignancy
 Squamous cell CA-Verrucous CA-Tongue* Bowen’s disease Basal cell CA
May occur at younger age
AJMG A 2010;152A:1575
J Dermatol 2008;35:154*Br J Plast Surg 1998;51:646

Rothmund-ThomsonSkin Management
 Photoprotection; ? Necessary (YES!) Emollients (dry skin, routine) ? Topical retinoids (hyperkeratoses)
 ? Topical salicylic acid (hyperkeratoses)
 ? Filing methods (hyperkeratoses/nails)
 Laser; Pulsed-dye, other lasers-ectatic/dilated vessels-hyperpigmentation-textural skin changes
 F/U of discrete skin lesions !!!

Cost of Moisturizers
Vaseline

$4.17

13 oz

Eucerin$15.0016 oz

Cetaphil$13.0016 oz

Cetaphil Restoraderm $18.00 +10 oz

Aquaphor$13.00

14 oz

Aveeno Eczema Care $12.00

6 oz

Cerave$17.0016 oz

Vanicream$14.00 +16 oz

Atopiclair (Rx)$36-$89.00

100 mlEpiceram (Rx)$89.00-$241

90 gm/3.2 oz

Sunscreen Labeling and Sun
Protection⚫ Broad Spectrum; requires both UVA coverage
AND SPF 15 or higher- ultimately max SPF 50+⚫ No “waterproof”, “sweatproof”, “sunblock”
claims⚫ Water resistant: 40 mins or 80 mins
⚫ Clothing and hats

Skin Tumors⚫ Biopsy of suspicious growths⚫ Excision- Mohs’ surgery⚫ Systemic therapies⚫ Topical management- Imiquimod- 5-Fluorouracil (5-FU)- Others!

Pediatric (Non-melanoma) Screening Recommendations(Gorlin/Basal Cell Nevus Syndrome)
J Pediatr 2019

Management – Skin CA*

Additional: curettage, excision, oral retinoids, vismodegib, sonidegib

Pediatr Dermatol 2020

Transformative Teams in Healthcare
Communication and Collaboration Seminar⚫Students in: Medicine, Nursing, Social Work,
Pharmacy, Educational Psychology⚫Parents help facilitate discussion-Experience with dx-What has gone well… what went badly-What could be better-Did the “team” function as a team?
-What were key things having greatest impact?

Looking ahead⚫Quality⚫Clinical and economic outcomes⚫Cross-disciplinary relationships (as part ofdisease models)⚫Patients/Families !!!

RECQ-Management⚫Multidisciplinary !!!

-Dermatology-Ophthalmology-Genetics-Oncology-Orthopedics-Psychosocial-? Dental-Others… Patients and Families!!!

To close “The good physician knows his (her) patients
through and through… Time, sympathy andunderstanding must be lavishly dispensed, but
the reward is to be found in that personal bondwhich forms the greatest satisfaction of thepractice of medicine. One of the essential
qualities of the clinician is interest in humanity,
for the secret of the care of the patient is in caring
for the patient.”
Peabody FW. JAMA 1927