131: Ectodermal Dysplasias Flashcards
What are the major ectodermal structures affected in ectodermal dysplasias?
The major ectodermal structures affected in ectodermal dysplasias include hair, teeth, nails, and sebaceous and sweat glands.
What are the clinical features of hypohidrotic ectodermal dysplasia?
Clinical features include hypotrichosis, hypohidrosis, hypodontia, skin abnormalities, facial features, and other features such as intellectual disability and eczema.
What is the mode of inheritance for hypohidrotic ectodermal dysplasia?
Hypohidrotic ectodermal dysplasia can be inherited in several ways: X-Linked, Autosomal Dominant, Autosomal Recessive, and HED with immune deficiency.
What are the potential complications associated with hypohidrotic ectodermal dysplasia?
Potential complications include respiratory issues, gastrointestinal issues, and growth issues.
What is the significance of the ectodysplasin signal transduction pathway in hypohidrotic ectodermal dysplasia?
Mutations in this pathway lead to interruption of interaction between epithelial cells and underlying mesenchyme.
What is the first step in diagnosing ectodermal dysplasia?
To determine the presence of sweating (hidrotic) or absence of sweating (hypohidrotic/anhidrotic).
What is the most common variant of hypohidrotic ectodermal dysplasia?
X-Linked HED (Christ-Siemens-Touraine Syndrome).
What are some facial features associated with hypohidrotic ectodermal dysplasia?
Common facial features include frontal bossing, depressed midface, saddle nose, and everted lips.
What is the epidemiology of hypohidrotic ectodermal dysplasia?
It occurs in 1 in 5,000 to 100,000 births across all racial groups.
What are some ENT and lung issues associated with hypohidrotic ectodermal dysplasia?
Issues include thick nasal secretions, sinusitis, recurrent respiratory infections, and increased frequency of asthma.
What is the genetic mutation associated with XLHED and its role?
XLHED is associated with an XLR mutation of EDA1 on Xq12-q13.1, which encodes the triggering ligand molecule ectodysplasin-A.
What are the clinical features of Hidrotic Ectodermal Dysplasia?
Clinical features include normal sweating and teeth, sparse wiry pale hair with progressive alopecia, and nail abnormalities.
What is the management approach for patients with HED?
Management includes maintenance of cool ambient temperatures, dental restoration, management of ENT complications, and recombinant ectodysplasin protein injections.
What is the genetic basis of P63-related ectodermal dysplasia syndromes?
They are caused by AD mutations of TP63 on 3q27, which encodes the p63 transcription protein.
What are the variants associated with P63-related ectodermal dysplasia syndromes?
Variants include AEC syndrome, Limb-mammary syndrome, ADULT syndrome, and EEC3 syndrome.
What is the prognosis for infants with HED?
Infants with HED are at increased risk of death due to hyperthermia and potentially other features of the disorder.
What is the genetic cause of Hidrotic Ectodermal Dysplasia?
It is caused by autosomal dominant mutations in the GJB6 gene, which encodes the intercellular junction protein connexin 30.
What diagnostic methods are used for Ectodermal Dysplasias?
Methods include panoramic view of the jaw, sweat test, skin biopsy, genetic testing, and histopathology.
What is the significance of the IKBKG mutation in HED with immune deficiency?
The IKBKG mutation on Xq28 encodes NF-kappa B cytoplasmic inhibitor, essential for immune function.
What management strategies should be implemented for a patient with recurrent upper respiratory infections and HED?
Strategies include maintaining cool ambient temperatures, dental restoration, managing ENT complications, and considering recombinant ectodysplasin protein injections.
What is the likely diagnosis for a child with sparse wiry pale hair and palmoplantar hyperkeratosis?
The likely diagnosis is hidrotic ectodermal dysplasia (Clouston syndrome), caused by autosomal dominant mutations in the GJB6 gene.
What additional clinical features might be present in a patient with a mutation in the IKBKG gene?
Additional features may include immune deficiency, recurrent infections, and eczema.
What are the clinical features of Rapp-Hodgkin syndrome?
Features include characteristic facial features, cleft palate, hypodontia, malformed auricles, and recurrent otitis media.
What distinguishes Rapp-Hodgkin syndrome from other ectodermal dysplasias?
It includes characteristic facial features such as a short nasal columella and maxillary hypoplasia.
What are the management strategies for Ankyloblepharon-Ectodermal Defects-Clefting Syndrome?
Strategies include use of light emollients, surgical lysis for ankyloblepharon, ocular hygiene, and a team approach for clefting repair.
What are the clinical features of Ectrodactyly-ED-Cleft Lip/Palate (EEC) syndrome?
Features include hair abnormalities, nail dystrophy, dry skin, ectrodactyly, and cleft palate.
What is the differential diagnosis for Ectrodactyly-ED-Cleft Lip/Palate (EEC) syndrome?
Differential diagnoses include odontotrichomelic syndrome, aplasia cutis congenita, and AEC syndrome.
What are the ectodermal features associated with Ankyloblepharon-Ectodermal Defects-Clefting Syndrome?
Features include collodion membrane at birth, dry thin skin, and variable nail dystrophy.
What are the clinical features of Ankyloblepharon-Ectodermal Defects-Clefting Syndrome?
Features include shiny red, cracking skin, chronic erosive dermatitis, and sparse body hair.
What is the main clinical difference between Rapp-Hodgkin syndrome and Ankyloblepharon-Ectodermal Defects-Clefting Syndrome?
Rapp-Hodgkin syndrome includes characteristic facial features, while AEC does not.
What are the management requirements for Ectrodactyly-ED-Cleft Lip/Palate Syndrome?
Requires a team approach for treatment of orofacial clefting, ophthalmologic issues, and limb defects.
What are the differential diagnoses for Ankyloblepharon-Ectodermal Defects-Clefting Syndrome?
Differential diagnoses include EEC syndrome, epidermolysis bullosa, and congenital ichthyosis.
What is a major distinguishing feature of EEC syndrome?
Ectrodactyly.
What are the differential diagnoses for Ankyoblepharon-Ectodermal Defects-Clefting Syndrome?
EEC syndrome, epidermolysis bullosa, congenital ichthyosis, and CHANDS.
What management strategies should be employed for a patient with AEC syndrome who has recurrent bacterial scalp infections?
Management includes wound care for the scalp, dilute bleach or other antimicrobial soaks, and surgical lysis for ankyloblepharon if necessary.
What diagnostic and management steps should be taken for a patient with EEC syndrome who presents with genitourinary abnormalities?
Diagnostic steps include renal ultrasonography and a high index of suspicion for urinary tract problems. Management requires a team approach, including treatment of orofacial clefting, ophthalmologic care, and addressing limb defects.
What is the feature called when a patient with AEC syndrome has strands of skin between the eyelids?
This feature is called ankyloblepharon filiforme adnatum (AFA), and it may require surgical lysis.
What is the mode of inheritance of EEC syndrome?
The mode of inheritance is autosomal dominant.
What are the clinical features of Odonto-onycho-dermal dysplasia (OODD)?
- Severe hypodontia to anodontia of the permanent teeth (most consistent)
- Tongue: Smooth, decreased fungiform and filiform papillae
- Nails: Dystrophic, congenital anonychia
- Hair: Absent at birth, dry, thin, sparse eyebrows
- Skin: Palmar erythema, palmoplantar hyperkeratosis, keratosis pilaris, palmoplantar hyperhidrosis, hypohidrosis on other body sites
What is the management approach for Schopf-Schulz-Passarge Syndrome (SSPS)?
- Restorative dentistry
- Monitor for potential increased risk of nonmelanoma skin cancer in SSP patients
What are the clinical features of Focal Dermal Hypoplasia (Goltz Syndrome)?
- Skin: Linear, punctate, streaky cribriform atrophy with telangiectasia along the lines of Blaschko
- Eyes: Microphthalmia, colobomas
- Teeth: Oligodontia, tooth dysplasia, enamel defects
- Skeletal: Vertical banding of bones, syndactyly, ectrodactyly, asymmetry, oligodactyly, short stature
- Intellectual disability
- Possible cardiac defects, abdominal wall defects, renal malformations
What are the stages of skin lesions in Incontinentia Pigmenti?
Stage | Description |
|——-|————-|
| Stage I | Perinatal inflammatory stage with erythema, vesicles, and pustules lasting for several days to weeks |
| Stage II | Verrucous and hyperkeratotic papules persistent for several weeks to months, lasting up to years |
| Stage III | Hyperpigmentation presenting around 6 months of age, persisting for several years into adulthood |
| Stage IV | Hypopigmentation and atrophy in previously affected areas
What are the differential diagnoses for Focal Dermal Hypoplasia?
- Conradi–Hünermann syndrome (chondrodysplasia punctata)
- Incontinentia pigmenti
- Microphthalmia and linear skin defects/microphthalmia
- Dermal aplasia
- Sclerocornea (MIDAS)
What genetic mutation is associated with WNT10A disorders?
A mutation of WNT10A (wingless-type MMTV integration site family, member 10A) on 2q35.
What are the two variants of WNT10A disorders?
Odonto-onycho-dermal dysplasia (OODD) and Schopf-Schulz-Passarge Syndrome (SSPS).
What is a common clinical feature of Odonto-onycho-dermal dysplasia (OODD)?
Severe hypodontia to anodontia of the permanent teeth.
What skin condition is associated with Schopf-Schulz-Passarge Syndrome (SSPS)?
Eyelid hidrocystomas plus OODD findings.
What is a significant risk for patients with Schopf-Schulz-Passarge Syndrome (SSPS)?
Potential increased risk of nonmelanoma skin cancer.
What is the epidemiology of Focal Dermal Hypoplasia (Goltz Syndrome)?
200 case reports.
What are some clinical features of Focal Dermal Hypoplasia (Goltz Syndrome)?
Linear, punctate, streaky cribriform atrophy with telangiectasia, atrophy, and fat herniation.
What is the epidemiology of Incontinentia Pigmenti?
1 in 50,000 to 150,000 newborns.
What are the four stages of skin lesions in Incontinentia Pigmenti?
Stage I: Perinatal inflammatory stage; Stage II: Verrucous and hyperkeratotic papules; Stage III: Hyperpigmentation; Stage IV: Hypopigmentation and atrophy.
What are some ocular features associated with Incontinentia Pigmenti?
Retinal neovascularization, strabismus, cataracts, optic atrophy, and retinal pigmentary abnormalities.
What genetic mutation is associated with odonto-onycho-dermal dysplasia (OODD)?
OODD is associated with autosomal recessive mutations in the WNT10A gene, which mediates catenin-mediated specific intracellular signaling.
What is the genetic etiology of focal dermal hypoplasia (Goltz syndrome)?
Focal dermal hypoplasia is caused by X-linked dominant mutations in the PORCN gene, which is involved in membrane targeting and secretion of Wnt proteins necessary for embryonic tissue development.
What are the stages of skin lesions in incontinentia pigmenti?
Stage I (perinatal inflammatory stage with erythema, vesicles, and pustules), Stage II (verrucous and hyperkeratotic papules), Stage III (hyperpigmentation), and Stage IV (hypopigmentation and atrophy).
What histopathological findings are expected in a patient with OODD?
Histopathological findings include orthokeratosis, hyperkeratosis, hypergranulosis, and mild acanthosis.
What additional systemic features might be present in a patient with focal dermal hypoplasia?
Additional systemic features may include cardiac defects, abdominal wall defects, and renal malformations.
What CNS manifestations might be present in a patient with incontinentia pigmenti?
CNS manifestations may range from a single seizure to encephalopathy, ischemic stroke, and significant developmental delay.
What is the mode of inheritance of odonto-onycho-dermal dysplasia (OODD)?
The mode of inheritance is autosomal recessive.
What biopsy findings are expected in a patient with focal dermal hypoplasia?
Biopsy findings include dermal hypoplasia and increased capillaries in the papillary dermis.
What is the mode of inheritance of incontinentia pigmenti?
The mode of inheritance is X-linked dominant.
What hair changes are expected in a patient with OODD?
Hair changes include absent hair at birth, dry and thin hair, and sparse eyebrows.
What skeletal features might be present in a patient with focal dermal hypoplasia?
Skeletal features include vertical banding of the bones (osteopathia striata), syndactyly, ectrodactyly, asymmetry, and short stature.
What ocular features might be present in a patient with incontinentia pigmenti?
Ocular features include retinal neovascularization, strabismus, cataracts, optic atrophy, and retinal pigmentary abnormalities.
What are the major and minor diagnostic criteria for X-linked dominant IKBKG syndrome?
Major criteria include any of the 4 stages of skin lesions.
Minor criteria include:
- Dental, ocular, CNS, hair, nail, palate, breast, and nipple anomalies
- Family history
- Multiple male miscarriages
- Histopathologic skin findings
What is the management approach for Tricho-Dento-Osseous (TDO) syndrome?
Management includes:
1. Dental care for enamel hypoplasia and taurodontism.
2. Symptom management for skeletal features such as increased bone density.
3. Genetic testing for diagnosis.
What are the clinical features of Tooth and Nail Syndrome (Witkop Syndrome)?
Clinical features include:
- Nail: Thin, small, and friable with koilonychia at birth; toenails more severely involved than fingernails.
- Teeth: Usually unaffected, may be small; secondary teeth may fail to erupt, with missing mandibular incisors, second molars, and maxillary canines.
- Etiology: AD mutation of MSX1 on 4p16.1.
What are the clinical features of Oculo-Dento-Digital Dysplasia (ODDD)?
Clinical features include:
- Hair: Sparse, dry, slow-growing scalp hair with absent or sparse eyelashes.
- Teeth: Enamel hypoplasia resulting in small, yellow, and friable teeth prone to decay.
- Eyes: Short palpebral fissures with microcornea and/or microphthalmia.
- Hands: Camptodactyly of the fourth and fifth fingers.
- Skeletal: Hyperostosis of the skull, broad ribs and clavicles, and abnormal trabeculation of the long bones.
What are the variants of Tricho-Rhino-Phalangeal Syndrome and their clinical features?
Variants:
1. TRPS I: Sparse hair, prominent nose, receding chin, cone-shaped epiphyses, hip malformations, short stature.
2. TRPS II: Features of TRPS I plus multiple exostoses type 1 and intellectual disabilities.
3. TRPS III: Features of TRPS I plus severe brachydactyly and more pronounced short stature.
What is the etiology of the condition associated with IKBKG mutation?
X-linked dominant, IKBKG (also called NEMO), Xp28, encodes the I-kappa-B kinase gamma subunit protein involved in cell protection from apoptosis.
What are the major diagnostic criteria for the condition related to IKBKG mutation?
Major criteria include any of the 4 stages of skin lesions.
What is a common clinical feature of Tooth and Nail Syndrome (Witkop Syndrome)?
Thin, small and friable nails, koilonychia at birth.
What is the etiology of Tooth and Nail Syndrome?
AD mutation of MSX1 on 4p16.1, which encodes the transcription factor Msx1.
What are the clinical features of Tricho-Dento-Osseous (TDO) Syndrome?
Kinky, extremely curly hair; enamel hypoplasia, hypocalcification, and taurodontism; thickened nails with splitting.
What is the management for Oculo-Dento-Digital Dysplasia (ODDD)?
Dental and eye care.
What are the clinical features of Tricho-Rhino-Phalangeal Syndrome?
Sparse hair, prominent nose, receding chin, cone-shaped epiphyses, hip malformations, and short stature.
What is the etiology of Tricho-Rhino-Phalangeal Syndrome?
AD mutation of TRPS1 on 8q23.2.
What is a common management strategy for Tricho-Rhino-Phalangeal Syndrome?
Growth hormone treatment, otoplasty, and rhinoplasty.
What genetic mutation is responsible for TDO syndrome?
TDO syndrome is caused by autosomal dominant mutations in the DLX3 gene, which encodes the transcription factor homeobox protein DLX-3.
What is the genetic etiology of oculo-dento-digital dysplasia (ODDD)?
ODDD is caused by autosomal dominant mutations in the GJA1 gene, which encodes connexin 43, a connexin protein of the intercellular junction.
What are the three variants of tricho-rhino-phalangeal syndrome (TRPS)?
The three variants are TRPS I (sparse hair, prominent nose, receding chin, cone-shaped epiphyses), TRPS II (features of TRPS I plus multiple exostoses and intellectual disabilities), and TRPS III (features of TRPS I plus severe brachydactyly and pronounced short stature).
What skeletal features are associated with TDO syndrome?
Skeletal features include increased bone density of the long bones and skull, craniosynostosis, and dolichocephaly.
What other skeletal abnormalities might be present in a patient with ODDD?
Other skeletal abnormalities include hyperostosis of the skull, broad ribs and clavicles, and abnormal trabeculation of the long bones.
What skeletal features might be present in a patient with TRPS?
Short stature and hip malformations.
What skeletal abnormalities might be present in a patient with oculo-dento-digital dysplasia (ODDD)?
Other skeletal abnormalities include hyperostosis of the skull, broad ribs and clavicles, and abnormal trabeculation of the long bones.
What genetic mutation is associated with tricho-rhino-phalangeal syndrome (TRPS I)?
TRPS I is associated with autosomal dominant mutations in the TRPS1 gene on 8q23.2.
What dental features are associated with tricho-dento-osseous (TDO) syndrome?
Dental features include enamel hypoplasia, hypocalcification, and taurodontism.
What dental features might be present in a patient with oculo-dento-digital dysplasia (ODDD)?
Dental features include enamel hypoplasia, resulting in small, yellow, and friable teeth prone to decay.
What variant of tricho-rhino-phalangeal syndrome (TRPS) is associated with multiple exostoses and intellectual disabilities?
This is TRPS II.
