Table I.
Clinical and molecular data of the different types of syndromic inherited poikiloderma
| OMIM number | RTS #268400 | PN #604173 | DKC #127550 #224230 #305000 #613987 #613988 #613989 #613990 #615190 #616353 | KS #173650 | WHSK 173700 | XP #278700 #278720 #278730 #278740 #278760 #278780 #610651 | BS #210900 | BGS #218600 | FA #227645 #227646 #227650 #300514 #600901 #603467 #609053 #609054 #610832 #613390 #613951 #614082 #614083 #615272 #616435 | POIKTMP #615704 |
|---|---|---|---|---|---|---|---|---|---|---|
| Inheritance | AR | AR | AD AR X-linked | AR | AD | AR | AR | AR | AR X-linked | AD |
| Onset of poikiloderma | 3-6 mo | 6 mo Prevalent acral distribution | 3-5 y Lacy reticular pigmentation rather than true poikiloderma | 2-3 y | 2-4 y Accentuated in flexural areas | Late childhood Abnormal freckling on the face before age 2 y ; real poikiloderma is rare | 1-2 y Butterfly distribution of face; initially telangiectatic erythema and not poikiloderma | Late onset (not in early infancy) | Variable Poikilodermoidbrownish pigmentation and hypo pigmentation | 6 mo |
| Palmoplantar keratoderma | About 30% of patients | Frequent | May be present | 65% | May be present | Absent | Absent | Absent | Absent | May be present |
| Blister | In early childhood; in sun-exposed areas | May be present | In areas of trauma | Acral; after trauma or sun exposure present at birth: fourth type of inherited epidermolysis bullosa | Absent | In neonate; in sun-exposed areas | Blister around the mouth | In infancy (face buttocks extremities) | Absent | May be present |
| Nail abnormalities | Pachyonychia is common | Pachyonychia | Major feature (lichen planus-like changes) | Frequent | Absent | Absent | Absent | Absent | Absent | May be present |
| Dental defects | Frequent (27%–59%); wide variety of malformations | Dental eruption delay; fragile carious teeth | Poor dentition; early dental loss | Periodontal disease | Absent | Absent | Occasional absence of lateral incisors | Delayed eruption of teeth | Severe generalized periodontitis | Absent (rarely poor dentition; recurrent gingivitis) |
| Mucous membrane lesions | Absent | Absent | Major feature: leukoplakia, stenosis | Orogenital leukokeratosis; mucous stenosis | Absent | Tongue leukoplakia | Absent | Anus anteposition; imperforated anus | Oral leukoplakia | No leukoplakia |
| Other dermatologic signs | Hypotrichosis/ alopecia photosensitivity; café-au-lait spots | Photosensitivity; sparse eyelash-eyebrows | No photosensitivity; absent fingerprints; alopecia; canities | Photosensitivity; skin fragility; skin atrophy; loss of dermal ridges; pseudosyndactyly pseudoainhum; phimosis ; anhidrosis | Sclerosis of palms and soles; linear hyperkeratosis and sclerotic bands in skin folds; calcinosis; clubbing fingers; Raynaud's phenomenon | Photosensitivity; xerosis | Photosensitivity; paucity of subcutaneous fat; loss of the lower eyelashes; café-au-lait spots | Swelling of the extremities | Café-au-lait spots | Hypohidrosis/heat intolerance; hypotrichosis/alopecia; lymphoedema of extremities; xerosis; eczema or psoriasis-like lesions; sclerosis of the digits; guttate hypo- melanosis |
| Ocular abnormalities | Cataract | Absent | Epiphora blepharitis retinopathy | Conjunctivitis; corneal erosion; ectropion of the lower eyelids | Absent | Photophobia; severe keratitis | Wide variety | Ocular proptosis; hypertelorism | Microphthalmia | May be present (cataract) |
| Skeletal defects Malformations |
Radial ray defects; patellar hypoplasia; frontal bossing; saddle nose | Craniofacial dysmorphism; hypermobile fingers with beak of swan appearence | Microcephaly; osteoporosis | Skull or mandibular abnormalities | Mandibuloacral dysplasia; maxillary bossing; micrognathia | Absent | Microcephaly; dolichocephaly; prominence of the nose and ears | Coronal cranio-synostosis; radial ray defects; patellar hypoplasia | Microcephaly; absent or abnormal thumbs and radii | May be present (scoliosis) small feet |
| Respiratory system | Bronchiectasis | Recurrent pulmonary infections | Diffuse interstitial pulmonary fibrosis | Normal | No pulmonary involvement | Normal | Pneumonia bronchiectasis chronic pulmonary disease | Normal | Pulmonary infections | Interstitial pulmonary fibrosis |
| Hematologic features | Leukopenia anemia | Permanent neutropenia | High frequency of bone marrow failure; pancytopenia | Absent | Absent | Absent | Myelodysplasia; low immunoglobulin counts | Absent | Major feature (bone marrow failure); myelodysplasia | Eosinophilia |
| Other visceral abnormalities | Chronic diarrhea in early childhood | Recurrent otitis media; splenomegaly | Liver cirrhosis | Severe colitis | Cardiac involvement; cardiac valvular diseases; aortic stenosis | Acquired microcephaly; neuro-degeneration (30%) in some variants | Immunodeficiency with recurrent infections; diabetes mellitus; gastroesophageal reflux; diarrhea; lower urinary tract obstruction | Heart-hand syndrome: radial abnormalities and defects in the heart | Type 2 diabetes (adults); ear abnormalities; hearing loss | Muscle contractures (triceps surae); muscle atrophy; weakness of proximal and distal muscles; liver involvement; pancreatic exocrine insufficiency |
| Physical development | Pre- and postnatal growth deficiency | Short stature | Short stature | Normal | Growth retardation | Normal | Pre- and postnatal growth deficiency | Short stature | Pre- and postnatal growth retardation | Growth retardation |
| Mental development | Normal | Normal or slightly delayed | Mental retardation | Normal | Normal | Intellectual deficiency (30%) | Normal or limited | Mental retardation in some patients | May be delayed | Normal |
| Malignancy | Osteosarcomas (childhood); skin carcinomas (adults); myelodysplasia; leukemia; lymphoma | Myelodysplasia; acute myeloid leukemia | Squamous cell carcinoma in and outside the areas of leukoplakia; Myelodysplasia ; acute myeloid leukemia | Mucocutaneous squamous cell carcinomas | Absent | Skin carcinomas, melanomas in early childhood; ocular and tongue neoplasms; leukemia | Types and sites of cancer very broad; early frequent (46%) | Osteosarcomas; skin carcinomas; lymphoma | Acute myeloid leukemia; squamous cell carcinomas of the head and neck, esophagus, and vulva; liver tumors | Absent (pancreatic cancer?) |
| Genetic defect | RECQL4 on 8q24.3∗ | C16orf57 on 16q21 |
TERC on 3q26.2 NOLA3 on 15q14 DKC1 on Xq28 NOLA2 on 5q35.3 WRAP53 on 17p13.1 TERT on 5p15.33 TINF2 on 14q12 RTEL1 on 20q13.33 PARN on 16p13.12 |
KIND1 on 20p12.3 | Unknown |
XPA on 9q22.33 XPC on 3p25.1 ERCC2 on 19q13.32 DDB2 on 11p11.2 ERCC4 on 16p13.12 ERCC5 on 13q33.1 ERCC3 on 2q14.3 |
BLM/RECQL3 on 15q26.1 | RECQL4 on 8q24.3∗ |
FANCC on 9q22.32 FANCD2 on 3p25.3 FANCA on 16q24.3 FAAP95 on Xp22.2 FANCE on 6p21.31 FANCF on 11p14.3 FANCI on 15q26 BRIP1 on 17q23.2 PALB2 on 16p12.2 RAD51C on 17q22 SLX4 X on 16p13.3 XRCC9 on 9p13.3 PHF9 on 2p16.1 ERCC4 on 16p13.12 UBE2T on 1q32.1 |
FAM111B on 11q12.1 |
Some of the discussed entities rather display a mottled disorder of pigmentation than true poikiloderma, which associates a reticulate hyperpigmentation, atrophy and telangiectases, but distinction between those 2 dermatologic phenotypes is not always done in published literature. Werner syndrome (OMIM #277700) is not mentioned because the symptoms appear in adulthood. It is associated with increased risk of malignancies (thyroid carcinoma, melanoma, soft-tissue sarcoma, meningioma).
AD, Autosomal dominant; AR, autosomal recessive; BGS, Baller-Gerold syndrome; BS, Bloom syndrome; DKC, dyskeratosis congenita; FA, Fanconi anemia; KS, Kindler syndrome; PN, poikiloderma with neutropenia; POIKTMP, hereditary fibrosing poikiloderma with tendon contractures, myopathy, and pulmonary fibrosis; WHSK, Weary hereditary sclerosing poikiloderma; XP, xeroderma pigmentosum.
∗
Mutations in RECQL4 are also associated with RAPADILINO syndrome, which overlaps clinically with RTS but without poikiloderma.