Genodermatosis

Neurofibromatosis

relatively common, 1 in 3000

Autosomal dominant

There are two main types:

1. Von Recklinghausen’s

neurofibromatosis (NF1; 85% of all

cases)

2. Bilateral acoustic neurofibromatosis

(NF2)

NF1

Cause

Mutation of NF1 gene, localized to chromosome 17q11.1.

The NF1 gene is a tumour suppressor gene, the product of which, neurofibromin, interacts with the product of the RAS proto-oncogene. This may explain the susceptibility of NF1 patients to a variety of tumours.

Inheritence as autosomal dominant trait

about half of index cases have no preceding family history.

Clinical features The physical signs include the following.

1. Café au lait patches

Six or more (light brown oval macules, usually developing in the first year of life.

2. Axillary freckling

in two-thirds of affected individuals (Crowe’s sign).

3. Neurofibromas

Any number

some small and superficial, others larger and deeper

Most are dome-like nodules, but others are irregular raised plaques. Some are firm, some soft and compressible through a deficient dermis (‘button-hole’ sign); others feel ‘knotty’ or ‘wormy’.

may not appear until puberty and become larger and more numerous with age.

4. Lisch nodules

Small circular pigmented hamartomas of the iris, appear in early childhood.

Clinical features, cont.

Nearly all NF1 patients meet the criteria for diagnosis by the age of 8 years, and all do so by 20 years.

The usual order of appearance of the clinical features is:

1. café au lait macules

2. axillary freckling

3. Lisch nodules

4. neurofibromas.

Clinical features, cont.

A segmental form of NF1 is caused by a

post-zygotic mutation.

Isolated neurofibromas are not

uncommon in individuals without

neurofibromatosis and are of little

consequence unless they are painful.

Complications

1. A neurofibroma will occasionally change

into a neurofibrosarcoma

2. Kyphoscoliosis

3. Learning impairment

4. Epilepsy

5. Renal artery stenosis

6. an association with

phaeochromocytoma

Management

Ugly or painful lesions, and any

suspected of undergoing malignant

change, should be removed.

The chance of a child of an affected

adult developing the disorder is 1 in 2

blood pressure checked regularly.

Tuberous sclerosis

uncommon condition, with a prevalence

about 1 in 12000 in children under 10

years

autosomal dominant trait

Fertility is reduced, so transmission

through more than two generations is

rare.

Cause

Inactivating mutations at two different

loci can, independently, cause clinically

identical tuberous sclerosis.

Both genes are tumour suppressors.

1. (TSC1 on chromosome 9q34)

2. (TSC2 on 16p13.3)

TSC2 gene mutations are responsible

for 80–90% of cases.

Clinical features

The skin changes include the following.

1. Ash leaf macules

Small oval white patches

occur in 80% of those affected

may be the only manifestation at birth.

2. Angiofibromas (known as adenoma sebaceum)

occur in 85% of those affected

develop at puberty as pink or yellowish acne-like papules on the face, often around the nose.

Clinical features, cont.

3. Periungual fibromas

occur in 50% of patients

develop in adult life as small pink sausage-like lesions emerging from the nail folds.

4. Connective tissue naevi (‘shagreenpatches’)

Are seen in 40% of patients.

Cobblestone, somewhat yellow plaques often arise in the skin over the base of the spine.

Other features

may include:

1. Epilepsy (in 75% of patients)

2. Mental retardation (in 50% of patients)

3. Ocular signs, including retinal phakomasand pigmentary abnormalities (in 50% of patients)

4. Hyperplastic gums

5. gliomas along the lateral walls of the lateral ventricles (80% of cases) and calcification of the basal ganglia

6. Renal and heart tumours.

Diagnosis and differential

diagnosis

Any baby with unexplained epilepsy

should be examined with a Wood’s light

to look for ash leaf macules.

Skull X-rays and computed tomography

scans of CNS and kidneys.

The lesions of adenoma sebaceum (a

misnomer, as histologically they are

angiofibromas) may be mistaken for

acne.

Management

Genetic counselling

Facial angiofibromas may improve

cosmetically after electrodessication,

dermabrasion or destruction by laser but

tend to recur

Xeroderma pigmentosum

heterogeneous group of autosomal

recessive disorders, characterized by

the defective repair of DNA after its

damage by ultraviolet radiation.

rare, affecting about 5 per million in

Europe.

Clinical features, cont.

There are many variants but all follow the

same pattern.

1. The skin is normal at birth.

2. Multiple freckles, roughness and keratoses

on exposed skin appear between the ages

of 6 months and 2 years

3. Photosensitivity increases thereafter.

4. The atrophic facial skin shows

telangiectases and small angiomas.

Clinical features, cont.

5. Many tumours develop on light-damaged skin: BCC, SCC, MM

Many patients die before the age of 20 years.

6. Eye problems are common and include photophobia, conjunctivitis and ectropion.

7. The condition may be associated with microcephaly, mental deficiency, dwarfism, deafness and ataxia (De Sanctis–Cacchione syndrome).

Treatment

Strict avoidance of sunlight, the use of

protective clothing, widebrimmed hats

and of reflectant sunscreens and dark

glasses.

If possible, patients should not go out by

day.

Early and complete removal of all

tumours is essential.

Radiotherapy should be avoided