GenodermatosisNeurofibromatosisTuberous sclerosis

Xeroderma pigmentosumIncontinentia pigmenti

Ehlers Danlos syndromePseudoxanthoma elasticum

NeurofibromatosisNeurofibromatosis::

Autosomal dominant condition, affect about 1 Autosomal dominant condition, affect about 1 in 3000 people, manifested by developmental in 3000 people, manifested by developmental changes in the nervous system, bone and skinchanges in the nervous system, bone and skin . .

There are many types, the most important two areThere are many types, the most important two are::11 . .Von Recklinghousen's neurofibromatosis (NF1) Von Recklinghousen's neurofibromatosis (NF1)

which accounts for 85% of caseswhich accounts for 85% of cases..22 . .Bilateral acoustic neurofibromatosis (NF2)Bilateral acoustic neurofibromatosis (NF2)..

Clinical featuresClinical features::11 . .Von Recklinghousen's neurofibromatosis Von Recklinghousen's neurofibromatosis

(NF1)(NF1)::•**Café au lait patchesCafé au lait patches (light brown oval (light brown oval

macules), usually developing in the first year of macules), usually developing in the first year of life. Finding of 6 or more lesions 1.5cm or more life. Finding of 6 or more lesions 1.5cm or more in diameter in adults, 0.5cm in diameter in in diameter in adults, 0.5cm in diameter in children, is diagnosticchildren, is diagnostic..

* *Axillary frecklingAxillary freckling in two-thirds of affected in two-thirds of affected individuals may extend to neck, may involve the individuals may extend to neck, may involve the inguinal, genetal and peineal areasinguinal, genetal and peineal areas . .

* *Variable numbers of skin Variable numbers of skin neurofibromasneurofibromas,, --They are soft tumors some small and They are soft tumors some small and

superficial, others larger and deepersuperficial, others larger and deeper..--ranging from flesh-coloured to pink, purple ranging from flesh-coloured to pink, purple

or brownor brown..--some are firm, some soft and compressible some are firm, some soft and compressible

which can be pushed down into the panniculus which can be pushed down into the panniculus by light pressure with fingers (button-hole sign)by light pressure with fingers (button-hole sign)..

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

--subcutaneous plexiform neurofibroma are subcutaneous plexiform neurofibroma are large nodules containing multiple large nodules containing multiple neurofibromas, on palpation they feel like a bag neurofibromas, on palpation they feel like a bag of wormsof worms..

**Small cicular pigmented hamartomas of the Small cicular pigmented hamartomas of the iris iris (Lisch nodules)(Lisch nodules)..

Other featuresOther features;; --Neurofibroma will occasionally change into Neurofibroma will occasionally change into

neurofibrosarcomaneurofibrosarcoma , ,--Mental deficiencyMental deficiency,,

--EpilepsyEpilepsy , ,--Renal artery stenosisRenal artery stenosis..

--CNS tumors, e.g. intracranial tumorsCNS tumors, e.g. intracranial tumors..--Bone lesions, e.g. macrocephaly, kyphoscoliosis,Bone lesions, e.g. macrocephaly, kyphoscoliosis,

short statureshort stature..--Pheochromocytoma Pheochromocytoma hypertension hypertension..

--HypogonadismHypogonadism..

Criteria for diagnosis of NF-1Criteria for diagnosis of NF-1

The presence of 2 or more of these criteria is The presence of 2 or more of these criteria is

diagnostic.diagnostic.

--Six or more café-au-lait macules of >5 mm in prepubertal Six or more café-au-lait macules of >5 mm in prepubertal & >15 mm in postpubertal& >15 mm in postpubertal..

--Two or more neurofibromas or one plexiform Two or more neurofibromas or one plexiform neurofibromaneurofibroma..

--Freckling in axilla or perineumFreckling in axilla or perineum..--Optic gliomaOptic glioma..

--Two or more Lisch nodulesTwo or more Lisch nodules..--Distinctive bony lesionDistinctive bony lesion..

--A 1st degree relative with NF-1 by these criteriaA 1st degree relative with NF-1 by these criteria..

22 . .Bilateral acoustic neurofibromatosis (NF2)Bilateral acoustic neurofibromatosis (NF2):: * *Bilateral acoustic neuromasBilateral acoustic neuromas..

* *Few, if any, cutaneous manifestationsFew, if any, cutaneous manifestations.. * *No Lisch nodulesNo Lisch nodules..

Other features; other tumours of the CNS Other features; other tumours of the CNS specially meningiomas and gliomasspecially meningiomas and gliomas..

Tuberous sclerosisTuberous sclerosis::Autosomal dominant condition, affect about 1in Autosomal dominant condition, affect about 1in

12000 children under 10 years12000 children under 10 years .

It is characterized by a triad of epilepsy, mental It is characterized by a triad of epilepsy, mental

retardation, skin lesions called adenoma sebaceum. retardation, skin lesions called adenoma sebaceum.

(usually angio-fibromas of face).(usually angio-fibromas of face).

Also called epiloa (epilepsy, low intelegence, Also called epiloa (epilepsy, low intelegence,

adenoma sebaceum).adenoma sebaceum).

Clinical featuresClinical features::Skin changesSkin changes::

* *Small oval white patches Small oval white patches (ash leaf macules) (ash leaf macules) occur in occur in 85% of cases, their number ranges from 1-100, 85% of cases, their number ranges from 1-100, important as they may be the only manifestation at important as they may be the only manifestation at birthbirth..

* *Adenoma sebaceum (angio-fibromaAdenoma sebaceum (angio-fibroma)), , present in 90% present in 90% of cases older than 4 years of age, persist indefinitely, of cases older than 4 years of age, persist indefinitely, pink or yellowish, translucent, waxy, acne-like pink or yellowish, translucent, waxy, acne-like papules (1-3mm) on the face, often around the nose, papules (1-3mm) on the face, often around the nose, cheeks and foreheadcheeks and forehead..

* *Peri-ungual fibromas (koenen tumors) Peri-ungual fibromas (koenen tumors) occur in 50% occur in 50% of cases, develop in adult life as pink sausage-like of cases, develop in adult life as pink sausage-like lesions emerging from the nail fold. Nails may show lesions emerging from the nail fold. Nails may show longitudinal groves, long leukonychia and short red longitudinal groves, long leukonychia and short red streaksstreaks..

* *Connective tissue nevi (shagreen patches) Connective tissue nevi (shagreen patches) are seen are seen in 40% of cases. Cobblestone, 1-8 cm in diameter, in 40% of cases. Cobblestone, 1-8 cm in diameter, yellow plaques often arise in the skin over the base of yellow plaques often arise in the skin over the base of the spine, composed of collagen and develop in the the spine, composed of collagen and develop in the

first decade of lifefirst decade of life . .Other skin findingsOther skin findings::

--Skin fibromas, café-au-lait spots, oral papillomatosis, Skin fibromas, café-au-lait spots, oral papillomatosis, gingival hyperplasiagingival hyperplasia..

Systemic featuresSystemic features:: * *EpilepsyEpilepsy . .

* *Mental retardationMental retardation.. * *Ocular signs, including retinal phakomas and Ocular signs, including retinal phakomas and

pigmentary abnormalitiespigmentary abnormalities.. * *Hyperplastic gumsHyperplastic gums..

* *Gliomas and calcification of the basal gangliaGliomas and calcification of the basal ganglia.. tumours.tumours.* Renal and heart* Renal and heart

* * Cystic lesions of lung.Cystic lesions of lung.

Diagnosis:Diagnosis:-Any baby with unexplained epilepsy should be -Any baby with unexplained epilepsy should be examined with wood’s light to look for ash leaf examined with wood’s light to look for ash leaf maculesmacules-Skull X-ray and CT scan help to exclude -Skull X-ray and CT scan help to exclude

involvement of the CNS and kidneysinvolvement of the CNS and kidneys

Xeroderma pigmentosumXeroderma pigmentosum::- - Autosomal recessive disorder, characterized by Autosomal recessive disorder, characterized by

the defective repair of DNA after its damage by the defective repair of DNA after its damage by UV radiation, extreme sun sensitivity, freckling UV radiation, extreme sun sensitivity, freckling and skin cancerand skin cancer . .

--The condition is rare affecting about 5 per The condition is rare affecting about 5 per million in Europemillion in Europe..

Clinical featuresClinical features:: * * The skin is normal at birthThe skin is normal at birth..

* * Multiple freckles, roughness and keratosis on Multiple freckles, roughness and keratosis on exposed skin appear between the ages of 6 months and exposed skin appear between the ages of 6 months and

2 years2 years . .**Photosensitivity increases thereafterPhotosensitivity increases thereafter..

* *The atrophic facial skin shows telangiectases and The atrophic facial skin shows telangiectases and small angiomassmall angiomas..

* *Many tumours develop on light-damaged skin; Many tumours develop on light-damaged skin; these include BCC, SCC, keratoacanthoma and these include BCC, SCC, keratoacanthoma and malignant melanoma. Skin cancers often appear malignant melanoma. Skin cancers often appear before age of 10.Many patients die before the before age of 10.Many patients die before the age of 20 years. Most of the cancers appear on age of 20 years. Most of the cancers appear on head and neckhead and neck..

* *Eye problems occur in 40% of cases and Eye problems occur in 40% of cases and include photophobia, conjunctivitis, corneal include photophobia, conjunctivitis, corneal opacities, neoplasm and ectropionopacities, neoplasm and ectropion..

* *The condition may be associated with The condition may be associated with microcephaly, mental deficiency, dwarfism, microcephaly, mental deficiency, dwarfism, deafness and ataxiadeafness and ataxia..

TreatmentTreatment::- - Skin cancers can be prevented by strict Skin cancers can be prevented by strict

avoidance of sunlightavoidance of sunlight..--Early and complete removal of all tumors Early and complete removal of all tumors

is essentialis essential . . --Retinoids can prevent the appearance of Retinoids can prevent the appearance of

new cancers but, side effects are new cancers but, side effects are significant, and rebound in the number of significant, and rebound in the number of cancers occur when the drug is stoppedcancers occur when the drug is stopped..

--Radiotherapy should be avoidedRadiotherapy should be avoided..

Incontinentia pigmentiIncontinentia pigmenti:: X-linked dominant disorder, usually lethal before X-linked dominant disorder, usually lethal before

birth in malesbirth in males.. Characterized by spattered Characterized by spattered pigmentation on the trunk preceded by vesicular and pigmentation on the trunk preceded by vesicular and

verrucous changesverrucous changes . .

Clinical features: There are three stages in the evolution of the skin There are three stages in the evolution of the skin

signssigns::11 . .Vesicular; Vesicular; linear groups of blisters occur more on linear groups of blisters occur more on

the limbs than trunk, most are evident by the time the the limbs than trunk, most are evident by the time the infant is 4-6 weeks old, occur in 87% of casesinfant is 4-6 weeks old, occur in 87% of cases..

22 . .Warty; Warty; after a few weeks or monthes the blisters dry after a few weeks or monthes the blisters dry up and the predominant lesions are papules with a up and the predominant lesions are papules with a verrucous hyperkeratotic surface, in two- thirds of verrucous hyperkeratotic surface, in two- thirds of cases, these usually resolve by one year of agecases, these usually resolve by one year of age..

33 . .Pigmented;Pigmented; after one year of age, a whorled, streaks after one year of age, a whorled, streaks or splashed macular pigmentation, following the lines or splashed macular pigmentation, following the lines of blaschko, ranging from slate-grey to brown color, of blaschko, ranging from slate-grey to brown color, replaces the warty lesions. Its bizarre patterning is areplaces the warty lesions. Its bizarre patterning is a

strong diagnostic pointer. This stage may last for strong diagnostic pointer. This stage may last for many years and fade away, leaving no sequelaemany years and fade away, leaving no sequelae..

A fourth stage may be seen in some adult women A fourth stage may be seen in some adult women manifesting faint hypochromic or atrophic linear manifesting faint hypochromic or atrophic linear lesions mostly on the extremetieslesions mostly on the extremeties..

Other skin manifestationsOther skin manifestations::Patchy alopecia, onychodystrophy, subungual tumors Patchy alopecia, onychodystrophy, subungual tumors and palmoplanter hyperhidrosisand palmoplanter hyperhidrosis..

CNS defects;CNS defects; mental retardation, epilepsy mental retardation, epilepsy or microcephaly, skull and palatal or microcephaly, skull and palatal abnormalities may also be foundabnormalities may also be found..Dental defects;Dental defects; delayed dentition, total delayed dentition, total absence of teeth, the incisors may be cone-absence of teeth, the incisors may be cone-or peg-shapedor peg-shaped..Occular defects;Occular defects; strabismus, cataract and strabismus, cataract and optic atrophyoptic atrophy..

TreatmentTreatment:: This is symptomatic and includes measures This is symptomatic and includes measures

to combat bacterial and candidal infection to combat bacterial and candidal infection during the vesicular phaseduring the vesicular phase..

Ehlers-Danlos syndromeEhlers-Danlos syndrome:: Caused by the abnormalities in the formation Caused by the abnormalities in the formation

or modification of collagen and the extracellular or modification of collagen and the extracellular matrixmatrix..Clinical featuresClinical features::

* *Hyperelasticity of the skinHyperelasticity of the skin.. * *Hyperextensibility of the jointsHyperextensibility of the joints..

* *Fragility of skin and blood vesselsFragility of skin and blood vessels.. * *Easy bruisingEasy bruising..

* *Cigarette paper scarsCigarette paper scars..

ComplicationsComplications:: Subluxation of joints, varicose veins, Subluxation of joints, varicose veins,

increased liability to develop hernias, increased liability to develop hernias, kyphoscoliosis, aortic aneurysm and kyphoscoliosis, aortic aneurysm and raptured large arteries, and intraocular raptured large arteries, and intraocular hemorrhagehemorrhage..

•Gorlin’s sign: can touch nose with tongue, sign of hyperextensibility

Pseudoxanthoma elasticumPseudoxanthoma elasticum:: This is a disorder of elastic tissue most This is a disorder of elastic tissue most

obviously in the skin, blood vessels and eyes, obviously in the skin, blood vessels and eyes, either autosomal dominant or recessiveeither autosomal dominant or recessive..PathologyPathology::

The elastic fibers in the mid-dermis become The elastic fibers in the mid-dermis become swollen and fragmented; their calcification is swollen and fragmented; their calcification is probably a secondary featureprobably a secondary feature..

The elastic tissue of blood vessels and of the The elastic tissue of blood vessels and of the retina may also be affectedretina may also be affected..

Clinical featuresClinical features:: The skin of the neck and axillae, and occasionally of The skin of the neck and axillae, and occasionally of

other body folds or oral mucosa, is loose and other body folds or oral mucosa, is loose and wrinkled. Groups of small yellow papules give these wrinkled. Groups of small yellow papules give these

areas a 'plucked chicken' appearanceareas a 'plucked chicken' appearance . .Other skin changesOther skin changes::

Lax redundant folds of skin, nuchal comedones, Lax redundant folds of skin, nuchal comedones, exagerated nasolabial folds, mental creasesexagerated nasolabial folds, mental creases..

Breaks in the retina show as angioid streaks, which Breaks in the retina show as angioid streaks, which are mostly appear before skin changesare mostly appear before skin changes . .

Arterial involvement may lead to peripheral, coronary Arterial involvement may lead to peripheral, coronary or cerebral arterial insufficiencyor cerebral arterial insufficiency..

ComplicationsComplications:: The most important areThe most important are : :

--hypertentionhypertention , ,--recurrent gut hemorrhagesrecurrent gut hemorrhages , ,

--ischemic heart disease, mitral valve prolapseischemic heart disease, mitral valve prolapse--epistaxisepistaxis,,

--cerebral hemorrhagecerebral hemorrhage..

There is no effective treatmentThere is no effective treatment..