Syndrome

Inheritance

Manifestations

Associated malignancy

1- Gardner's syndrome

Autosomal dominant

Intestinal adenomatous polyposis, epidermal cysts (especially on the face and scalp), fibromas and desmoid tumours (benign fibrous neoplasms from muscular aponeurosis), osteomas of facial bones and dental anomalies

Malignant change of colonic polyposis into colonic adenocarcinoma in about 50% of the cases

2- Peutz-Jeghers syndrome

Autosomal dominant

Mucocutaneous pigmentation (especially perioral), gastrointestinal polyposis (mainly in small intestine)

Adenocarcinoma of stomach, duodenum, and colon in 2%-3% of cases

3- Palmoplantar keratoderma (Howel-Evans syndrome)

Autosomal dominant

Keratoderma of palms and soles (tylosis)

Oesophageal carcinoma

Syndrome

Inheritance

Manifestations

Associated malignancy

4- Naevoid basal cell epithelioma syndrome (Gorlin's syndrome)

Autosomal dominant

Multiple basal cell epitheliomas, formes frustes (pits) of palms and soles, mandibular keratocysts, skeletal anomalies of ribs and scoliosis, calcification of falx cerebri, mental retardation

Cerebellar medulloblastomas, fibrosarcomas of mandible or maxilla, and ameloblastomas in jaw cysts

5- Von Hippel-Lindau's syndrome

Autosomal dominant

Cutaneous haemangiomas and café-au-lait spots, retinal angiomatosis

CNS haemangioblastomas, phaeochromocytoma, renal and pancreatic carcinoma

6- Neurofibromatosis (Von Recklinghausen's disease)

Autosomal dominant

Cutaneous neurofibromas, plexiform neuroma along course of nerve, café-au-lait spots, axillary freckling, Lish nodules of iris, oral papillomatous tumours, GIT lesions, endocrine disturbances, renovascular hypertension, kyphoscoliosis, mental deficiency in 33%

Sarcomatous change in neurofibromas, optic nerve glioma, astrocytomas, Schwannomas, nephroblastoma (Wilm's tumour), rhabdomyosarcoma, leukaemia and retinoblastoma

7- Tuberous sclerosis (epiloia)

Autosomal dominant

Angiofibromas, periungual fibromas, shagreen patch in lumbosacral area, ash-leaf-shaped white macules, epilepsy, mental deficiency, and hamartomas in many organs, e.g. cardiac rhabdomyomas

Malignant sarcomatous change especially in rhabdomyomas and angiomyolipomas, renal cell carcinoma

8- Multiple Endocrine Neoplasia - type III (multiple mucosal neuromas, Gorlin's syndrome)

Autosomal dominant

Multiple mucosal neuromas at birth or infancy: flesh-coloured papules or nodules on the tongue, lips and other mucosal sites, thick protuberant lips, marfanoid habitus, muscle weakness, musculoskeletal anomalies

Medullary thyroid carcinoma, phaeochromocytoma (often bilateral)

Syndrome

Inheritance

Manifestations

Associated malignancy

9- Cowden's syndrome (multiple hamartoma syndrome)

Autosomal dominant

Multiple trichilemmomas (hyperkeratotic, flat-topped, wart-like) especially around the mouth, nose and ears; warty, cobblestone hyperplasia of the tongue and buccal mucosa; acral warty keratoses; GIT polyposis; fibrocystic disease of breasts in females; thyroid: goitres and adenomas

Adenocarcinoma of the breast in about 50% of affected women, thyroid carcinoma

10- Muir-Torre syndrome

Autosomal dominant

Sebaceous tumours (yellowish): adenoma (commonest), epithelioma, carcinoma; keratoacanthomas (crater)

Carcinoma of the colon (the commonest), non-Hodgkin's lymphoma. However, incidence of metastases is relatively low.

11- Bazex syndrome (follicular atrophoderma)

Autosomal dominant

Follicular atrophoderma, multiple basal cell epitheliomas, hypotrichosis

Leukaemia

12- Werner's syndrome (adult premature ageing, pangeria)

Autosomal recessive

Premature ageing starting after puberty, premature canities, baldness, dry atrophic skin, mottled hyperpigmentation, telangiectasia, lower limb ulcers, short stature, senile appearance, generalized loss of subcutaneous fat, cataracts, joint contractures, early menopause, diabetes mellitus

Sarcomas, melanoma, leukaemia, meningiomas and astrocytoma. However, the commonest cause of death is arteriosclerosis.

13- Primary (idiopathic) haemochromatosis

Autosomal recessive, male : female = 10 : 1

Onset: gradual between 40 and 60 years, grey-brown pigmentation of the skin, diabetes mellitus, liver cirrhosis, hypogonadism, increased iron deposition in internal organs

Primary hepatocellular carcinoma

Syndrome

Inheritance

Manifestations

Associated malignancy

14- Chédiak-Higashi syndrome

Autosomal recessive

Partial albinism and photophobia: fair skin and hair, pale retinae and translucent irides; giant cytoplasmic granules are present in leucocytes; patients have a marked susceptibility to infections; neurological abnormalities; death most commonly occurs in childhood as a result of infection or of the "accelerated phase"

In the terminal "accelerated phase", patients develop fever, jaundice, hepatosplenomegaly, lymphadenopathy, pancytopenia, haemorrhages and a deterioration of neurological changes. Although strongly suggestive of lymphoma the infiltrate of affected organs is reported to be a reactive, diffuse, mononuclear-cell type, rather than neoplastic

15- Ataxia telangiectasia (Louis-Bar syndrome)

Autosomal recessive

Progressive cerebellar ataxia, oculocutaneous telangiectasia, immune deficiency of both the cell-mediated and humoral type, recurrent sinus and pulmonary infections

There is a high incidence of neoplasia (10%) usually in or before the teenage years, the majority of which are lymphoproliferative or leukaemic

Syndrome

Inheritance

Manifestations

Associated malignancy

16- Bloom's syndrome (congenital telangiectatic erythema and stunted growth)

Autosomal recessive

Principally affects the Ashkenazi-Jewish race; sun-sensitive telangiectatic erythema of the face starting in infancy and often extending to the forearms and hands; small (but proportionate) stature and slender build; dolichocephaly; low IgA and IgM levels with frequent bacterial infections; other anomalies may be present, e.g. café-au-lait patches, high-arched palate, syndactyly, annular pancreas, congenital heart disease and testicular atrophy (androgen-secreting portions are spared permitting normal puberty)

Acute leukaemia, lymphoma, carcinoma of the gastrointestinal tract

17- Dyskeratosis congenita (Zinsser-Engman-Cole syndrome)

Sex-linked recessive. Autosomal dominant inheritance has also occurred.

Dystrophy of the nails with failure of the nails to form a nail plate, white thickening of the oral mucosa ± of the anal mucosa, extensive areas of reticulate pigmentation of the skin suggestive of poikiloderma atrophicans vasculare but with less atrophy and telangiectasia, Fanconi* type of anaemia may develop with severe pancytopenia

Carcinoma may develop in leucoplakia-like mucous membrane lesions, pancreatic carcinoma, Hodgkin's disease, leukaemia

18- Wiskott-Aldrich syndrome

Sex-linked recessive (males only)

Thrombocytopenic purpra, eczema, recurrent infections, death usually occurs during first decade from infection, bleeding, or malign

Malignant lymphoma (especially in small intestine), leukaemia