Condition |
Associated features |
Associated/observed tumors |
Inheritance pattern |
Gene(s) |
References |
Constitutional mismatch repair deficiency |
Multiple CALMs Hypopigmented skin macules
|
Haematological malignancies Brain tumours Gastrointestinal cancers |
Biallelic |
MLH1 MSH2 MSH6 PMS2
|
11–14 |
Xeroderma pigmentosum |
Severe sun-sensitivity Marked freckling of sun-exposed areas Premalignant actinic keratoses
Xerosis and poikiloderma
Ocular involvement: keratitis/corneal opacification and vascularization
Increased lid pigmentation; loss of eyelashes
Acquired microcephaly Diminshed/absent deep tendon reflexes Progressive sensorineural hearing loss Progressive cognitive impairment |
Skin cancers
Solid malignancies Ocular neoplasia |
AR |
XPA ERCC3 XPC DDB2 ERCC4 ERCC5 ERCC1 POLH ERCC2
|
15–18 |
Rothmund–Thomson syndrome |
Poikiloderma Photosensitivity, leading to a 'butterfly' facial rash
Juvenile cataracts Skeletal dysplasia/bone abnormalities |
Osteosarcoma
Skin cancers
Brain tumours Lynch syndrome-associated tumours |
AR |
RECQL4
|
19–21 |
Fanconi anaemia |
Pigmentary changes
Short stature and skeletal anomalies, especially upper limb Eye malformations and hearing loss CNS malformations and developmental delay Urogenital, cardiac, gastrointestinal and oral abnormalities Up to 25–33% have no congenital anomalies |
Haematological malignancy (especially acute myeloid leukaemia) Solid tumours including brain tumors (BRCA2/PALB2), Wilms(BRCA2/PALB2),SCC, hepatic carcinoma |
AR |
FANCD1 (BRCA2)
FANCJ/BRIP1/BACH1
FANCN (PALB2)
FANCA FANCC FANCD2 FANCE FANCF FANCG FANCI FANCLFANCM
RAD51C (FA-like) |
5,22–31 |
|
|
|
X-linked |
FANCB
|
|
Ataxia telangiectasia |
Oculocutaneous telangiectasias Pigmentation abnormalities (CALMs) Poikiloderma Seborrhoeic dermatitis Occasionally: atopic anddiscoid eczema, follicularkeratosis, dry skin,hirsutism, vitiligo
Progressive cerebellar ataxia Oculomotor apraxia Choreoathetosis Frequent infections/immunodeficiency |
Lymphoma, leukaemia Stomach, breast and other solid tumours |
AR |
ATM
|
32–41 |
Bloom syndrome |
Sun-sensitive 'butterfly' facial rash Pigmentary abnormalities
Low birth weight Short stature/growth deficiency Craniofacial dysmorphisms (narrow cranium; prominent nose and ears) Immunodeficiency |
Haematological and solid malignancies |
AR |
BLM
|
42,43 |
Werner syndrome |
Lack of pubertal growth spurt
Scleroderma-like skin changes, mallelolar skin ulcers, subcutaneous atrophy, premature grey hair
Cataracts Diabetes mellitus Myocardial infarction Hoarse voice |
Sarcoma Osteosarcoma Melanoma Thyroid carcinoma |
AR |
WRN (RECQL2) |
44–46 |
Naevoid basal cell (Gorlin–Goltz) syndrome |
Palmar/plantar pits, facial milia Meibomian cysts of the eyelids Sebaceous and dermoid cysts Skin tags around the neck
Falx calcification Odontogenic jaw keratocysts Macrocephaly; frontal bossing, coarse facies Cleft lip and palate Skeletal anomalies Ocular anomalies |
Basal cell carcinoma Medulloblastoma Cardiac fibromas Ovarian fibromas (rarely malignant) |
AD |
PTCH
|
7,47–53 |
Costello syndrome |
Deep palmar and plantar creases Curly, or fine sparse hair Loose, soft skin Perinasal and perianal papillomata
Failure to thrive; short stature Developmental delay or mental retardation Coarse facial features Diffuse hypotonia; joint laxity; tight Achilles tendons Cardiac involvement |
Rhabdomyosarcoma Neuroblastoma Transitional cell carcinoma of the bladder (adolescence) |
AD |
HRAS
|
8,54–56 |
Neurofibromatosis type 1 |
CALMs, axillary/inguinal freckling, neurofibromas, schwannomas
CNS glial tumours |
Malignant peripheral nerve sheath tumour |
Sporadic, AD |
NF1
|
57,58 |
Legius syndrome |
CALMs, axillary/inguinal freckling, neurofibromas, schwannomas
CNS glial tumours |
Juvenile myelomonocytic leukaemia |
AD |
SPRED1
|
59,60 |
Neurofibromatosis type 2 |
Acoustic neuromas, meningiomas of the brain, and schwannomas of the dorsal roots of the spinal cord. Rarely, cutaneous features as for NF1
|
Possible association with mesothelioma |
AD |
NF2
|
4,61,62 |
Tuberous sclerosis complex |
Hamartomas in the skin, brain, heart, kidneys and lungs
Cutaneous angiofibromas (often facial), periungual fibromata, shagreen patch, 'ash-leaf' macules, achrocordons, dental pitting and poliosis
Epilepsy, learning difficulties, psychological problems and autism |
Cardiac rhabdomyomas, renal angiomyolipomas and Wilms tumours |
AD |
TSC1 TSC2
|
4,63 |
Multiple endocrine neoplasia type 1 |
Parathyroid tumours, gastrointestinal endocrine tumours and adenohypophyseal tumours
Lipomas, facial angiofibromas and collagenomas
CALMs
|
Meningioma, Ependymoma |
AD |
RET
|
4,64,65 |
Multiple endocrine neoplasia type 2A |
Phaeochromocytoma and primary hyperparathyroidism
Cutaneous neuromas, itchy papules and amyloidosis
|
Medullary thyroid carcinoma |
AD |
RET
|
4,66–68 |
Multiple endocrine neoplasia type 2B |
Phaeochromocytoma, a marfanoid habitus and mucosal and digestive ganglioneuromatosis
Mucosal neuromas (around the eyes and mouth) and CALMs
|
Medullary thyroid carcinoma |
AD |
RET
|
4,66,70 |
Carney complex |
Cutaneous, cardiac, endocrine and neural myxomas
Lentigines, blue naevi and CALMs
Multiple endocrine tumours Large-cell calcifying Sertoli cell tumour and psammomatous melanotic schwannomas |
Thyroid, colon, pancreatic and ovarian carcinoma and others |
AD |
PRKAR1A
Chromosome 2p16 |
71,72 |
Beckwith–Wiedemann syndrome |
Exomphalos, macroglossia, hemihypertrophy, macrosomia, linear indentation of the ear lobe, posterior helical ear pit, zosteriform rash, facial naevus flammeus, cutaneous haemangiomas
|
Hepatoblastoma, Wilms tumour, neuroblastoma or rhabdomyosarcoma |
Imprinted |
IGF2 CDKN1C (p57)
NSD1
LIT1
|
58,73,74 |
Wiskott–Aldrich syndrome |
Microthrombocytopenia (often causing haemorrhage) Immunodeficiency
Eczema
Autoimmunity Cancer risk |
Leukaemia Myelodysplasia Lymphoma |
X-linked |
WAS gene |
76,77 |
Chediak–Higashi syndrome |
Generalized hypopigmentation (may include partial albinism)
Recurrent infections Mild coagulopathy Neurological symptoms |
ALL T-cell lymphoma |
AR |
CHS1/LYST
|
78–80 |
X-linked agammaglobulinaemia |
Immune deficiency
Cellulitis/impetigo Eczema
Dermatomyositis-like syndrome
|
Colorectal Gastric |
X-linked |
BTK
|
81–84 |
X-linked dyskeratosis congenita |
Abnormal skin pigmentation Nail dystrophy Mucosal leukoplakia
|
Haematological malignancy Head and neck SCC Skin and anorectal SCC Gastrointestinal |
X-linked (AR and AD forms also exist) |
DKC1
|
85,86 |
Neuroblastoma |
Neuroblastoma, cutaneous metastases, CALMs
|
Neuroblastoma |
AD |
Various including:
KIF1B PHOX2B ALK
|
87–89 |
Nail-patella syndrome |
Dysplastic nails with absent or dyspastic patellae. Other features include elbow dysfunction, glaucoma and renal dysfunction |
Possible association with colorectal carcinoma |
AD |
LMX1B
|
90,91 |
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