SYNDROMES WITH DEFECTIVE DNA REPAIR

Question 1

Xeroderma Pigmentosum

Answer 1

Defect in nucleotide excision repair gene, ocular abnormalities (photophobia, keratitis, corneal opacification, vascularization), neurologic abnormalities (progressive deafness)
•XP variant (mutation in DNA polymerase ): no neurologic abnormalities
• DeSanctis–Cacchione syndrome (Gr. A): s evere neurologic abnormalities (MR, deafness, ataxia)

Question 2

Cockayne Syndrome

Answer 2

AR-COCKAYN E – eight letters (ERCC 8 ), Cachectic dwarfism, Ocular (salt/pepper RP),Cataracts, Avoid sun, Ears (“mickey mouse”)

Question 3

Trichothiodystrophy (PIBIDS)

Answer 3

AR, ERCC2 (XPD protein) and ERCC3 (XPB protein)
PIBIDS: Photosensitivity (50%), ichthyosis (variable severity), brittle hair (alternating bright and dark bands known as “tiger tail,” flattened hair shafts like a ribbon), intellectual impairment, decreased fertility

Question 4

Bloom Syndrome

Answer 4

(RecQL2, some sources say RecQL3), BLooM – 2 O’s (RecQL 2) Butterfly rash, Leukemia, iMmune deficiency, ↓ Ig M

Question 5

Rothmund–Thomson Syndrome (Poikiloderma Congenitale)

Answer 5

• AR, R ECQL4 (DNA helicase)
• Presents with photodistributed erythema and vesicles on face in first few months of life, evolves into poikiloderma and extends to buttocks and
extremities, premalignant acral keratoses, alopecia, cataracts, hypoplastic thumbs/ radii/ulnae, ↑ risk osteosarcoma , normal intelligence

Question 6

Dyskeratosis Congenita (Zinsser-Engman-Cole Syndrome)

Answer 6

XLR, DKC1 gene mutation, encodes protein dyskerin
AD, hTR (human telomerase RNA component) and hTERT (human telomerase reverse transcriptase)
DYSkeRaTOSis – DYStrophy (nails), mR , Thrombocytopenia, Oral premalignant leukoplakia, Sun avoidance (poikiloderma)

Question 7

Ataxia-Telangiectasia Syndrome

Answer 7

AR, ATM, Presents first with ataxia (2–3 years old)
Defects in cellular and humoral immunity (↓ IgA, IgG, IgE), severe and frequent sinopulmonary infections, ↑ lymphoreticular malignancy, ↑ breast CA

Question 8

Fanconi Syndrome

Answer 8

AR, ↑ chromosomal breakage
• Presents with diffuse hyperpigmentation, multiple CALMs, pancytopenia, ↑ SCC, ↑ solid organ CA, ↑ leukemia, hypoplasia of radius/thumb