Other genodermatoses Flashcards
What are the key features of phenylketonuria?
Phenylalanine accumulation results in CNS toxicity
= developmental delay, neruological impairment, behavioural issues, seizures, psychiatric conditions
Cutaneous features:
- reduced melanin production (diffuse pigment reduction)
- sweat with a musty odour
- scleroderma like changes of the proximal extremities
- Atopic dermatitis in 50%
A child (~ 2 years old) has the following features
- Developmental delay
- Diffuse pigment dilution
- Sweat with a musty odour
- Progressive scleroderma like changes of the proximal extremities
What genetic condition might they have? what is the inheritance? what is the primary defect?
Phenylketonuria
Autosomal recessive condition;
Deficiency of the phenylalanine hydroxylase, resulting in accumulation of phenylalanine in the body.
Which conditions (relevant to derm) are detected on newborn screening?
Phenylketonuria
Fabry disease
A child (<10 years) with a background of developmental delay presents with well demarcated erythema, scaling and dryness over photoexposed areas
On further history, they have been havign intermittent episodes of ataxia.
What diagnosis should you consider?
Hartnup disease
(an AR condition characterised by Aminoaciduria and tryptophan deficency)
DDx: SLE, photosensitive drug eruption, PMLE etc.
What is Hartnup disease?
An autosomal recessive condition due to defective renal and intestinal amina acid transport –> resulitng in aminoaciduria and tryptophan deficiency
Signs and symptoms include:
- developmental delay
- intermittent ataxia, nystagmus, tremor
- photosensitvie “pellagra-like” dermatoses
How is hartnup disease detected? and how is it treated?
Elevated urine AA levels
Rx: high protein diet and niacin replacement
Angiokeratoma’s are seen in the following metabolic disorders:
Fabry’s disease (X linked)
Fucidosis (AR)
Galactosialidosis (AR)
Aspartylglucosaminuria (AR)
Kanzaki disease (AR)
Beta - Mannosidosis (AR)
Sialidosis (AR)
GM1 gangliosidosis (AR)
A young boy presents with Acral dysthesia, hypohidrosis and multipe angiokeratomas.
What is your preferred diagnosis? What other features would you look for on exam?
Fabry disease
DDx: fucidosis, other inherited metabolic disorders
Dysmorphic features:
- bushy eyebrows
- broad nasaal brdge
- periorbital fullness
- thick lips
- prominent earlobes
Slit lamp exam for whorled corneal opacities
CVS exam - cardiomegaly, arrythmia
Abdo exam - organomegaly
A child presents with black ear wax, blue grey sclera and skin discolouration (blue / grey) of the axillae and ear cartilage.
What is your preferred dx? What else would you ask on history?
Alkaptonuria
History of dark urine on standing
What are the features of MEN 2A
Gene = RET
Inheritance = AD
Cutaneous: (PMLN)
- Pruritis
- lichen amyloidosis
- macular amyloidsosis
- notalgia parasthetica
Endocrine (TAP)
- Thyroid (C-cell hyperplasia, medullary carcinoma)
- Adrenal (phaeochromocytoma)
- Parathyroid (hyperplasia or adenoma)
What are the features of MEN 2B?
Gene: RET
Inheritance: AD
Cutanoues:
- Multiple neuromas (mucosal)
- CALMs
- hypopigmented macules
- Peri-oral lentigenes
- hypertrichosis
Endocrine: (TAG)
- thyroid (adenomas)
- Adrenal (phaechromocytomas)
- GI (ganglioneruomatosis)
What are the featues of MEN1
Gene = MEN1
Inheritance = AD
Cutanoues: (CFLC)
- Collangenomas
- Facial angiofibromas
- Lipomas
- confetti like hypopigmented macules
- CALMS
- gingival papules
Endocrine: (PPP)
- Parathyroid (adenomas, hyperplasia)
- Pancreatic tumours (islet cell adenoma, insulinomas, galactomas)
- Pituitary tumours (prolactinoma)
A patient has multiple mucosal neuromas, what genetic condition should you consider? and what Ix are required?
Concern for MEN 2B
Thyroid USS, Colonoscopy and adrenal scan
Cowden’s syndorme is due to which gene defect?
PTEN
Outline the diagnostic criteria for COWDENs syndrome?
3 major criteia (in LDD, macrocephaly or GI harmatomas)
OR
2 major and 3 minor criteria
Major criteria
1/ Multiple mucocutanoeus lesions (> 3 of each for any of the following)
* Multiple Facial Tricholemmomas
* Acral keratoses and palmar pits
* Mucosal neruomas
* Oral papilomas (tongue, gingiva)
2/ Pigemented macules on the glans penis
3/ Macrocephaly
4/ Lhermitte-Duclos disease (cerebellar tumour)
5/ Breast cancer
6/ follcular thyroid cancer
7/ GI harmatomas
**Minor criteria **
1/ vascular anomalies
2/ Lipomas
3/ Testicular lipomatosis
4/ ASD
5/ interlectual disability
6/ Renal cell carcinoma
7/ colon cancer
8/ Esophageal glycogenic acanthosis
9/ medullar or papillary thyroid cancer
10/ thyroid structural lesions
What is Muir Torre syndrome?
An autosomal dominant condition.
Characterised by:
1/ adenocarcinoma of the colon
+/- genitourinary carcinoma
2/ sebaceous neoplasa and keratoacanthomas
What woud you look for on histo that may suggest Muir Torre Syndrome?
Keratoacanthoma with sebaceous differentiation
Loss of MSH2, MSH1, MSH6 expression on immunohistochemistry
A patient has two sebaceous neoplasms recently excised on the trunk. This occurs in the context of multiple previous keratoacanthomas.
What genetic condition might this patient have? what is the gene? what important history question should you ask?
Muir Torre syndrome
Gene: MSH2 > MSH1 > MSH6
Phx, FHX of bowel cancer
What genetic condition is associated with multiple epidermal cysts?
Gardener sydnrome
What is Wiskott Aldrich Syndrome?
X linked condition
Due to loss of function of the WAS gene which encodes the WASP protein
Characterised by:
- recurrent sinopulmonary infections
- eczematous deramtitis
- bleeding secondary to thrombocytopaenia
What are the key features of Wiskott Aldrich syndrome?
Bleeding
Recalcitrant eczematous dermatitis
- occurs in the first few months of life
- typical AD pattern
- exfoliative dermatitis
Recurrent sinopulmonary disease
Why do patients with Wiskott aldrich syndrome have recurrent sinopulmonary infections and easy bleeding?
Abnormal T and B cell function
NK cell dysfunction
Platelet dysfunction
Wiskott Aldrich syndrome is associated with which conditions?
AI conditions
IgE mediated conditions - urticaria, food allergy, asthma
Lymphoma
What gene is affected in Wiskott aldrich syndrome?
WAS gene - encodes the WASP protein
What is the inheritance of severe combined immunodeficency?
XLR (mostly) or AR
What are the defects / genes involved in severe combined immunodeficency
XLR= defect in the Y chain of the IL - 2 receptor
AR = adenosine diaminase deficency
resulting in defects in both humoral and cell mediated immunity
How does Severe combined immunodeficency present?
materno - fetal acute GVHD - morbilliform or seb derm like eruption
Cutanoeus features can mimic:
- LP
- acrodermatitis enteropathica
- LCH
- Inchythosiform erythroderma
- systemic sclerosus
Omenn syndrome - exfoliative dermatiis
What is Omenn syndrome?
Severe combined immunodefiency secondary to RAG 1 /2 gene mutations
Exfoliative dermatitis
Alopecia
Lymphadenopathy Hepatosplenomegaly
Diarrhoea
Eosinophillia
Leukocytosis
Elevated IgE
Deramatofibroma protuberans is ass with which genetic defect?
ADA ( adenosin diaminase deficency)
