Genodermatoses😍

Neurofibromatosis Type 1 (NF1)

• Mnemonic: NF
• Newly 17 girl → she was soft with pedunculated (Neurofibromas → soft, pedunculated) boobs → she wore skin coloured () bra and red coloured () panties and button (button hole sign) in her navel hole ()
• She was dominant (AD)
• she won a house for her reckless (Von reckling house) behavious
• She got wings (sphenoid wing dysplasia)
• She want to cafe (Cafe laut) → met with 6 guys (> 6 lesions) →
• She put lens in iris (iris hamartoma) and wore a leash (Lisch nodules)
• invited as a crew (Crows sign) → to lick her axiilla (In axilla)
• Her legs got bent (Bowing of legs)
• She lost vision → Optic N glioma

• Presence of neurofibromas

• Inheritance: Autosomal dominant pattern

• Chromosome: 17

• Also called: Von Recklinghausen's disease

Features (mnemonic: CAFES):

• Cafe au lait spots:
• > 6 lesions
• > 5 mm in prepubertal individuals
• > 15 mm in postpubertal individuals

• Axillary or inguinal freckling:
• Axillary freckling also called Crowe sign

• Fibromas:
• Two or more neurofibromas OR
• One plexiform neurofibroma
• (present along the nerve in an elongated fashion)
• Neurofibroma:
• Soft, pedunculated,
• skin-colored to red-colored lesions,
• present anywhere
• Feels very soft, called button-hole sign

• Eye:
• Optic nerve glioma (m/c CNS tumor in NF - 1)
• Iris hamartomas (Lisch nodules)

• Skeletal abnormalities:
• Sphenoid wing dysplasia OR
• Leg bowing

• Additional features:
• Positive family history:
• History of NF in a first-degree relative
• CNS features:
• Epilepsy
• Low intelligence
• Malignancies:
• Dry and astrocytoma

Diagnosis:

• Two or more of these features

Neurofibromatosis Type 2 (NF-2)

Genetics and Key Feature

• Gene: Mutation in Merlin protein (also called Schwannomin)

• Chromosome: Located on chromosome 22

• Accounts for 3–4% of all neurofibromatosis cases

• Mnemonic: 22 yr old Merlin was showoff (Schwannomin)

Pathognomonic finding:

• Bilateral Vestibular Schwannoma (B/L VS) OR

• Acoustic Neuroma

• B/L ice cream cone appearance in cerebellopontine angle.
• B/L Vestibular schwannoma.

• Chromosome no. 22.

• Mnemonic: Show man () eating Ice cream () with 22 (Chr 22) year old

Diagnostic Criteria for NF-2

• Diagnosis can be made with any one of the following:
• Positive family history of NF-2 (+)
• Unilateral Vestibular Schwannoma
• Plus any of:
• Meningioma >>
• Glioma
• Neurofibroma
• Juvenile posterior subcapsular lenticular opacities

Tuberous Sclerosis Complex (TSC)

• Also called:
• Bourneville's disease
• Epiloia (Epilepsy, Low intelligence, Adenoma sebaceum)

• Autosomal dominant inheritance.

• Gene defect:
• TSC1 (Chromosome 9).
• Hamartin gene
• TSC2 (Chromosome 16).
• Tubulin gene

• Chromosome: 9 and 16

• Features (mnemonic: HAMARTOMAS):
• Hamartoma (general)
• Wunderlich Syndrome:
• Massive retroperitoneal hemorrhage
• Lenk's triad: mass, hypotension, flank pain
• Mnemonic: Wonder (Wunderlich) that fat occur in kidney
• Wonder Land → Wunder Lenk
• Adenoma sebaceum
• Mental retardation
• Ash leaf spots
• Rhabdomyoma
• Tubers
• Optic hamartomas
• Mitral regurgitation
• Astrocytoma
• Seizures

Presentation:

1. Cutaneous lesion +

2. Epileptic
• CNS:
• 1st year: Infantile spasm.
• Management: Vigabatrin.
• Leads to mental retardation.
• After 1 year: Focal seizures.
• Management: Carbamazepine (lifelong).
• MRI brain
• Subependymal astrocytoma (potato-like).

Important skin features:

• Mnemonic: Hamara (Hamartomatous) Ashley (Ash leef) green color (sha green) tube (tuberous sclerosis) il keri koya (koenen) de conmference (confetti) nu poi → Bougainvilla (Bourneville's disease) de kambeduth Adich (Adenoma sebaceoum) → Red papules () vann

Subependymal nodules

• Can enlarge to form SEGA (Subependymal Giant Cell Astrocytoma)

• Most common site: foramen of Monro

• Mnemonic: Tube (TS) nte thazhe nodules (Subependymal nodules) vachitt Munroe (Foramen of munro) poi → Giant (SEGA) aale kanan

Adenoma sebaceum:

• Misnomer (not related to sebaceous glands)

• Cutaneous angiofibroma / Facial Angiofibroma

• Acneiform lesion with butterfly distribution

• Red papules on cheeks, nose, nasolabial folds, and chin

• Asymptomatic

• Starts appearing at 3-4 years of age
• increases during puberty

• No Comedones, no pustules (unlike acne)

Ash leaf macules / spots:

• Early cutaneous feature at birth

• Leaf-shaped or lancet-shaped hypopigmented lesions

Shagreen patch:

• Leathery patch

• Collagenoma

• orange peel consistency

Koenen's tumors:

• Periungual tumors (periungual fibromas)

• Subungual fibroma causing nail crack

• Fleshy growth at root of nail.

• Seen along nail folds

Confetti-like macules

Gingival fibromas

Cafe au lait macules (may be present)

Systemic features:

• Hamartomas affecting:
• Neurological system
• Eyes
• Lungs
• Cardiac system
• Renal system

Important Information

• For infantile spasm:
• ACTH.

• Infantile spasm + Tuberous sclerosis:
• Vigabatrin.

2. Peutz-Jeghers Polyp:

• Autosomal Dominant

• Genetics: STK11 or LKB1
• Mnemonic: "111" for age and gene

• CHR 19

• Age: Around 11 years.

• Mnemonic:
• Putes Jeggers → P, J
• Pigmentation (lips, mucosa, digits and perianal skin), 
• JEjunal polyp (more in jejunum)*

• "P" for periorificial lentigines
• Lentigines along the oral mucosa

• Polyp appearance: 
• Tree-like, Christmas tree, or arborizing.
• Branches made of smooth muscle.
• Mnemonic: Jegher → Jungle, jejunum → Tree

• m/c Location of Polyps: Jejunum

• Increased Risk of Cancer (non-colonic):
• Pancreatic (100x higher risk)
• Duodenal
• Thyroid

• Clinical Features:
• m/c presentation: Intussusception
• Pathognomonic finding: Perioral melanosis

• Mnemonic:
• Dominant Jungle girl → 11 year old (age 11) → In LKG (LKB1 ) → pigmented lips (perioral melanosis, lentigines) → smooth muscles (branches smooth muscles) → walk with a stick (STK11) → lives in a tree (arborising) → has maturity of 19 years (chr 19)

Epidermolysis Bullosa (EB)

• Meaning: Epidermis and formation of bulla

• Also called: Mechanobullous disorder

• Bullae form on mechanical trauma

1. Neonatal pemphigus

2. Epidermolysis bullosa

3. Congenital syphilis

4. Chronic bullous disease of childhood

Types:

• Congenital (3 types):
1. EB Simplex (EBS)
2. Junctionalis
3. Dystrophic

• Acquired (EB acquisita):
• Antibodies against collagen 7
• Leads to subepidermal disorder

Congenital EB

• Categorized by defect location:

• Mechanism:
• Gene defect → structural defect → skin split (no autoantibody formation)

• Presentation:
• Early in life
• Skin splits upon handling or massage
• At site of mechanical force or trauma

• Diagnosis:
• Skin biopsy: Intra- or subepidermal split
• Diagnostic test: Electron microscopy
• DIF: Not performed (no antibody formation, so no fluorescence)

• Treatment:
• Gene therapy (only treatment available)