genodermatosis

genetic disorders

NeurofibromatosisTuberous sclerosisXeroderma pigmentosumIncontinentia pigmentiEhlers–Danlos syndromePseudoxanthoma elasticum

Neurofibromatosis

This relatively common disorder affects about 1 in 3000 people and is inherited as an autosomal dominant trait. There are two main types: von Recklinghausen’sneurofibromatosis (NF1; which accounts for 85% of all cases) and bilateral acoustic neurofibromatosis (NF2); these are phenotypically and genetically distinct.

Von Recklinghausen’s neurofibromatosis (NF1)1.Six or more cafй au lait patches (light brown ovalmacules), usually developing in the firstyear of life.2.Axillary freckling in two-thirds ofaffected individuals.3.Variable numbers of skin neurofibromas, some smalland superficial, others larger and deeper, ranging fromflesh-coloured to pink, purple or brown.Most are dome-like nodules, but others are irregularraised plaques. Some are firm, some soft and compressiblethrough a deficient dermis (‘button-hole’sign); others feel ‘knotty’ or ‘wormy’. Neurofibromasmay not appear until puberty and become larger andmore numerous with age.4.Small circular pigmented hamartomas of the iris(Lisch nodules), appear in early childhood.Nearly all NF1 patients meet the criteria for diagnosisby the age of 8 years, and all do so by 20 years.The usual order of appearance of the clinical featuresis cafй au lait macules, axillary freckling, Lisch nodulesand neurofibromas.

Neurofibromatosis (NF1) Skin-colored and pink-tan, soft papules and nodules on the backare neurofibromas. The lesions first appeared during late childhood. Two large cafe-au-lait macules on the back.The large, soft, ill-defined, subcutaneous nodule on the right lower back and on the right posterior axillary line are plexiform neuromas.

Neurofibromatosis (NF1) Several larger (> 1 cm) cafe-au-lait macules on the upper chestand multiple small macules on the axillae (axillary “freckling”) in a brown-skinned female. Myriads of early, small,pink-tan neurofibromas on the chest, breasts, and neck.

Neurofibromatosis (NF1) An excessively large number of small and large, pedunculated neurofibromas on the chest of a 56-year-old woman who also had a severely distorted face due to multiple neurofibromas and plexiform neuromas.

Lisch nodules: best seen with a slit-lamp

Tuberous sclerosis
inherited as an autosomal dominant trait, with variable expressivity even within the same family


Clinical featuresThe skin changes include the following.• Small oval white patches (‘ash leaf macules’) occurin 80% of those affected. These are important as theymay be the only manifestation at birth.• Adenoma sebaceum occur in 85% of thoseaffected. They develop at puberty as pink or yellowishacne-like papules on the face, often around the nose.• Peri-ungual fibromas occur in 50% of patients.These develop in adult life as small pink sausage-likelesions emerging from the nail folds .• Connective tissue naevi (‘shagreen patches’) are seenin 40% of patients. Cobblestone, somewhat yellowplaques often arise in the skin over the base of thespine.Other features may include:• epilepsy (in 75% of patients);• mental retardation (in 50% of patients);• ocular signs, including retinal phakomas and pigmentaryabnormalities (in 50% of patients);• hyperplastic gums;

Any baby with unexplained epilepsy should be examined with a Wood’s light to look for ashleaf macules.

Tuberous sclerosis: ash-leaflet hypopigmented macules A . Three well-demarcated,elongated (ash-leaflet shaped), hypomelanotic macules on the lower leg of a child with tan skin. B. Ash-leaflethypomelanotic macules in pale skin are better visualized under Wood light where they light up.

Tuberous sclerosis. Adenoma sebaceum,understandably, was referred to the acne clinic

Tuberous sclerosis: angiofibromas Confluent, small, angiomatous (erythematous, glistening)papules on the cheek and nose. These lesions were not present during the first few years of life; appearedonly after the age of 4 years.

The peri-ungual fibromas of tuberous sclerosis arefound in adult patients.

Tuberous sclerosis A. Periungual fibroma (Koenen tumor). B. Shagreen patch, slightlyelevated, skin-colored. This represents a connective tissue nevus.

Xeroderma pigmentosum

Xeroderma pigmentosum is a heterogeneous group of autosomal recessive disorders, characterized by the defective repair of DNA after its damage by ultraviolet radiation.



• The skin is normal at birth.• Multiple freckles, roughness and keratoses on exposed skin appear between the ages of 6 months and 2 years Photosensitivity increasesthereafter.• The atrophic facial skin shows telangiectases and small angiomas.• Many tumours develop on light-damaged skin: these include basal cell carcinomas, squamous cell carcinomas,keratoacanthomas and malignant melanomas.Many patients die before the age of 20 years.• Eye problems are common and include photophobia,conjunctivitis and ectropion.• The condition may be associated with microcephaly,mental deficiency, dwarfism, deafness and ataxia.

Xeroderma pigmentosum: obvious freckling onneck. Scars on nose mark the spots where tumours have been removed.

Incontinentia pigmenti

This rare condition is an X-linked dominant disorder,usually lethal before birth in males.


Clinical featuresThere are three stages in the evolution of the skinsigns.1 Vesicular. Linear groups of blisters occur more onthe limbs than trunk.2 Warty. After a few weeks the blisters dry up and thepredominant lesions are papules with a verrucoushyperkeratotic surface.3 Pigmented. A whorled or ‘splashed’ macular pigmentation,ranging from slate-grey to brown, replacesthe warty lesions. Its bizarre patterning is a strongdiagnostic pointer.

Ehlers–Danlos syndrome Eleven subtypes are now recognizedCauseAll varieties of the Ehlers–Danlos syndrome are basedon abnormalities in the formation or modificationof collagen and the extracellular matrix, but are notnecessarily a result of mutations in the collagen genesthemselves.

Clinical features• Hyperelasticity of the skin.• Hyperextensibility of the joints.• Fragility of skin and blood vessels.• Easy bruising.• Curious (‘cigarette paper’) scars.

Pseudoxanthoma elasticum

This is the classical inherited connective tissue disorder affecting the elastic structures in the body amostobviously in the skin, blood vessels and eyes.

Pseudoxanthoma elasticum

Clinical featuresThe skin of the neck and axillae, and occasionally of other body folds, is loose and wrinkled. Groups of small yellow papules give these areas a ‘plucked chicken’ appearance .Breaks in the retina show as angioid streaks, which are grey poorly defined areas radiating from the optic nerve head.Arterial involvement may lead to peripheral, coronary or cerebral arterial insufficiency.The ‘plucked chicken’ appearance of pseudoxanthoma in the antecubital fossa.

Complications The most important are hypertension, recurrent gut haemorrhages, ischaemic heart disease and cerebral haemorrhage. Diagnosis and treatment The diagnosis is made clinically and confirmed by the histology. There is no effective treatment.