131: Ectodermal Dysplasias

Question 1

What are the major ectodermal structures affected in ectodermal dysplasias?

Answer 1

The major ectodermal structures affected in ectodermal dysplasias include hair, teeth, nails, and sebaceous and sweat glands.

Question 2

What are the clinical features of hypohidrotic ectodermal dysplasia?

Answer 2

Clinical features include hypotrichosis, hypohidrosis, hypodontia, skin abnormalities, facial features, and other features such as intellectual disability and eczema.

Question 3

What is the mode of inheritance for hypohidrotic ectodermal dysplasia?

Answer 3

Hypohidrotic ectodermal dysplasia can be inherited in several ways: X-Linked, Autosomal Dominant, Autosomal Recessive, and HED with immune deficiency.

Question 4

What are the potential complications associated with hypohidrotic ectodermal dysplasia?

Answer 4

Potential complications include respiratory issues, gastrointestinal issues, and growth issues.

Question 5

What is the significance of the ectodysplasin signal transduction pathway in hypohidrotic ectodermal dysplasia?

Answer 5

Mutations in this pathway lead to interruption of interaction between epithelial cells and underlying mesenchyme.

Question 6

What is the first step in diagnosing ectodermal dysplasia?

Answer 6

To determine the presence of sweating (hidrotic) or absence of sweating (hypohidrotic/anhidrotic).

Question 7

What is the most common variant of hypohidrotic ectodermal dysplasia?

Answer 7

X-Linked HED (Christ-Siemens-Touraine Syndrome).

Question 8

What are some facial features associated with hypohidrotic ectodermal dysplasia?

Answer 8

Common facial features include frontal bossing, depressed midface, saddle nose, and everted lips.

Question 9

What is the epidemiology of hypohidrotic ectodermal dysplasia?

Answer 9

It occurs in 1 in 5,000 to 100,000 births across all racial groups.

Question 10

What are some ENT and lung issues associated with hypohidrotic ectodermal dysplasia?

Answer 10

Issues include thick nasal secretions, sinusitis, recurrent respiratory infections, and increased frequency of asthma.

Question 11

What is the genetic mutation associated with XLHED and its role?

Answer 11

XLHED is associated with an XLR mutation of EDA1 on Xq12-q13.1, which encodes the triggering ligand molecule ectodysplasin-A.

Question 12

What are the clinical features of Hidrotic Ectodermal Dysplasia?

Answer 12

Clinical features include normal sweating and teeth, sparse wiry pale hair with progressive alopecia, and nail abnormalities.

Question 13

What is the management approach for patients with HED?

Answer 13

Management includes maintenance of cool ambient temperatures, dental restoration, management of ENT complications, and recombinant ectodysplasin protein injections.

Question 14

What is the genetic basis of P63-related ectodermal dysplasia syndromes?

Answer 14

They are caused by AD mutations of TP63 on 3q27, which encodes the p63 transcription protein.

Question 15

What are the variants associated with P63-related ectodermal dysplasia syndromes?

Answer 15

Variants include AEC syndrome, Limb-mammary syndrome, ADULT syndrome, and EEC3 syndrome.

Question 16

What is the prognosis for infants with HED?

Answer 16

Infants with HED are at increased risk of death due to hyperthermia and potentially other features of the disorder.

Question 17

What is the genetic cause of Hidrotic Ectodermal Dysplasia?

Answer 17

It is caused by autosomal dominant mutations in the GJB6 gene, which encodes the intercellular junction protein connexin 30.

Question 18

What diagnostic methods are used for Ectodermal Dysplasias?

Answer 18

Methods include panoramic view of the jaw, sweat test, skin biopsy, genetic testing, and histopathology.

Question 19

What is the significance of the IKBKG mutation in HED with immune deficiency?

Answer 19

The IKBKG mutation on Xq28 encodes NF-kappa B cytoplasmic inhibitor, essential for immune function.

Question 20

What management strategies should be implemented for a patient with recurrent upper respiratory infections and HED?

Answer 20

Strategies include maintaining cool ambient temperatures, dental restoration, managing ENT complications, and considering recombinant ectodysplasin protein injections.

Question 21

What is the likely diagnosis for a child with sparse wiry pale hair and palmoplantar hyperkeratosis?

Answer 21

The likely diagnosis is hidrotic ectodermal dysplasia (Clouston syndrome), caused by autosomal dominant mutations in the GJB6 gene.

Question 22

What additional clinical features might be present in a patient with a mutation in the IKBKG gene?

Answer 22

Additional features may include immune deficiency, recurrent infections, and eczema.

Question 23

What are the clinical features of Rapp-Hodgkin syndrome?

Answer 23

Features include characteristic facial features, cleft palate, hypodontia, malformed auricles, and recurrent otitis media.

Question 24

What distinguishes Rapp-Hodgkin syndrome from other ectodermal dysplasias?

Answer 24

It includes characteristic facial features such as a short nasal columella and maxillary hypoplasia.

Question 25

What are the management strategies for Ankyloblepharon-Ectodermal Defects-Clefting Syndrome?

Answer 25

Strategies include use of light emollients, surgical lysis for ankyloblepharon, ocular hygiene, and a team approach for clefting repair.

Question 26

What are the clinical features of Ectrodactyly-ED-Cleft Lip/Palate (EEC) syndrome?

Answer 26

Features include hair abnormalities, nail dystrophy, dry skin, ectrodactyly, and cleft palate.

Question 27

What is the differential diagnosis for Ectrodactyly-ED-Cleft Lip/Palate (EEC) syndrome?

Answer 27

Differential diagnoses include odontotrichomelic syndrome, aplasia cutis congenita, and AEC syndrome.

Question 28

What are the ectodermal features associated with Ankyloblepharon-Ectodermal Defects-Clefting Syndrome?

Answer 28

Features include collodion membrane at birth, dry thin skin, and variable nail dystrophy.

Question 29

What are the clinical features of Ankyloblepharon-Ectodermal Defects-Clefting Syndrome?

Answer 29

Features include shiny red, cracking skin, chronic erosive dermatitis, and sparse body hair.

Question 30

What is the main clinical difference between Rapp-Hodgkin syndrome and Ankyloblepharon-Ectodermal Defects-Clefting Syndrome?

Answer 30

Rapp-Hodgkin syndrome includes characteristic facial features, while AEC does not.

Question 31

What are the management requirements for Ectrodactyly-ED-Cleft Lip/Palate Syndrome?

Answer 31

Requires a team approach for treatment of orofacial clefting, ophthalmologic issues, and limb defects.

Question 32

What are the differential diagnoses for Ankyloblepharon-Ectodermal Defects-Clefting Syndrome?

Answer 32

Differential diagnoses include EEC syndrome, epidermolysis bullosa, and congenital ichthyosis.

Question 33

What is a major distinguishing feature of EEC syndrome?

Answer 33

Ectrodactyly.

Question 34

What are the differential diagnoses for Ankyoblepharon-Ectodermal Defects-Clefting Syndrome?

Answer 34

EEC syndrome, epidermolysis bullosa, congenital ichthyosis, and CHANDS.

Question 35

What management strategies should be employed for a patient with AEC syndrome who has recurrent bacterial scalp infections?

Answer 35

Management includes wound care for the scalp, dilute bleach or other antimicrobial soaks, and surgical lysis for ankyloblepharon if necessary.

Question 36

What diagnostic and management steps should be taken for a patient with EEC syndrome who presents with genitourinary abnormalities?

Answer 36

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.

Question 37

What is the feature called when a patient with AEC syndrome has strands of skin between the eyelids?

Answer 37

This feature is called ankyloblepharon filiforme adnatum (AFA), and it may require surgical lysis.

Question 38

What is the mode of inheritance of EEC syndrome?

Answer 38

The mode of inheritance is autosomal dominant.

Question 39

What are the clinical features of Odonto-onycho-dermal dysplasia (OODD)?

Answer 39

- 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

Question 40

What is the management approach for Schopf-Schulz-Passarge Syndrome (SSPS)?

Answer 40

- Restorative dentistry - Monitor for potential increased risk of nonmelanoma skin cancer in SSP patients

Question 41

What are the clinical features of Focal Dermal Hypoplasia (Goltz Syndrome)?

Answer 41

- 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

Question 42

What are the stages of skin lesions in Incontinentia Pigmenti?

Answer 42

| 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

Question 43

What are the differential diagnoses for Focal Dermal Hypoplasia?

Answer 43

- Conradi–Hünermann syndrome (chondrodysplasia punctata) - Incontinentia pigmenti - Microphthalmia and linear skin defects/microphthalmia - Dermal aplasia - Sclerocornea (MIDAS)

Question 44

What genetic mutation is associated with WNT10A disorders?

Answer 44

A mutation of WNT10A (wingless-type MMTV integration site family, member 10A) on 2q35.

Question 45

What are the two variants of WNT10A disorders?

Answer 45

Odonto-onycho-dermal dysplasia (OODD) and Schopf-Schulz-Passarge Syndrome (SSPS).

Question 46

What is a common clinical feature of Odonto-onycho-dermal dysplasia (OODD)?

Answer 46

Severe hypodontia to anodontia of the permanent teeth.

Question 47

What skin condition is associated with Schopf-Schulz-Passarge Syndrome (SSPS)?

Answer 47

Eyelid hidrocystomas plus OODD findings.

Question 48

What is a significant risk for patients with Schopf-Schulz-Passarge Syndrome (SSPS)?

Answer 48

Potential increased risk of nonmelanoma skin cancer.

Question 49

What is the epidemiology of Focal Dermal Hypoplasia (Goltz Syndrome)?

Answer 49

200 case reports.

Question 50

What are some clinical features of Focal Dermal Hypoplasia (Goltz Syndrome)?

Answer 50

Linear, punctate, streaky cribriform atrophy with telangiectasia, atrophy, and fat herniation.

Question 51

What is the epidemiology of Incontinentia Pigmenti?

Answer 51

1 in 50,000 to 150,000 newborns.

Question 52

What are the four stages of skin lesions in Incontinentia Pigmenti?

Answer 52

Stage I: Perinatal inflammatory stage; Stage II: Verrucous and hyperkeratotic papules; Stage III: Hyperpigmentation; Stage IV: Hypopigmentation and atrophy.

Question 53

What are some ocular features associated with Incontinentia Pigmenti?

Answer 53

Retinal neovascularization, strabismus, cataracts, optic atrophy, and retinal pigmentary abnormalities.

Question 54

What genetic mutation is associated with odonto-onycho-dermal dysplasia (OODD)?

Answer 54

OODD is associated with autosomal recessive mutations in the WNT10A gene, which mediates catenin-mediated specific intracellular signaling.

Question 55

What is the genetic etiology of focal dermal hypoplasia (Goltz syndrome)?

Answer 55

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.

Question 56

What are the stages of skin lesions in incontinentia pigmenti?

Answer 56

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).

Question 57

What histopathological findings are expected in a patient with OODD?

Answer 57

Histopathological findings include orthokeratosis, hyperkeratosis, hypergranulosis, and mild acanthosis.

Question 58

What additional systemic features might be present in a patient with focal dermal hypoplasia?

Answer 58

Additional systemic features may include cardiac defects, abdominal wall defects, and renal malformations.

Question 59

What CNS manifestations might be present in a patient with incontinentia pigmenti?

Answer 59

CNS manifestations may range from a single seizure to encephalopathy, ischemic stroke, and significant developmental delay.

Question 60

What is the mode of inheritance of odonto-onycho-dermal dysplasia (OODD)?

Answer 60

The mode of inheritance is autosomal recessive.

Question 61

What biopsy findings are expected in a patient with focal dermal hypoplasia?

Answer 61

Biopsy findings include dermal hypoplasia and increased capillaries in the papillary dermis.

Question 62

What is the mode of inheritance of incontinentia pigmenti?

Answer 62

The mode of inheritance is X-linked dominant.

Question 63

What hair changes are expected in a patient with OODD?

Answer 63

Hair changes include absent hair at birth, dry and thin hair, and sparse eyebrows.

Question 64

What skeletal features might be present in a patient with focal dermal hypoplasia?

Answer 64

Skeletal features include vertical banding of the bones (osteopathia striata), syndactyly, ectrodactyly, asymmetry, and short stature.

Question 65

What ocular features might be present in a patient with incontinentia pigmenti?

Answer 65

Ocular features include retinal neovascularization, strabismus, cataracts, optic atrophy, and retinal pigmentary abnormalities.

Question 66

What are the major and minor diagnostic criteria for X-linked dominant IKBKG syndrome?

Answer 66

**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

Question 67

What is the management approach for Tricho-Dento-Osseous (TDO) syndrome?

Answer 67

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.

Question 68

What are the clinical features of Tooth and Nail Syndrome (Witkop Syndrome)?

Answer 68

**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.

Question 69

What are the clinical features of Oculo-Dento-Digital Dysplasia (ODDD)?

Answer 69

**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.

Question 70

What are the variants of Tricho-Rhino-Phalangeal Syndrome and their clinical features?

Answer 70

**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.

Question 71

What is the etiology of the condition associated with IKBKG mutation?

Answer 71

X-linked dominant, IKBKG (also called NEMO), Xp28, encodes the I-kappa-B kinase gamma subunit protein involved in cell protection from apoptosis.

Question 72

What are the major diagnostic criteria for the condition related to IKBKG mutation?

Answer 72

Major criteria include any of the 4 stages of skin lesions.

Question 73

What is a common clinical feature of Tooth and Nail Syndrome (Witkop Syndrome)?

Answer 73

Thin, small and friable nails, koilonychia at birth.

Question 74

What is the etiology of Tooth and Nail Syndrome?

Answer 74

AD mutation of MSX1 on 4p16.1, which encodes the transcription factor Msx1.

Question 75

What are the clinical features of Tricho-Dento-Osseous (TDO) Syndrome?

Answer 75

Kinky, extremely curly hair; enamel hypoplasia, hypocalcification, and taurodontism; thickened nails with splitting.

Question 76

What is the management for Oculo-Dento-Digital Dysplasia (ODDD)?

Answer 76

Dental and eye care.

Question 77

What are the clinical features of Tricho-Rhino-Phalangeal Syndrome?

Answer 77

Sparse hair, prominent nose, receding chin, cone-shaped epiphyses, hip malformations, and short stature.

Question 78

What is the etiology of Tricho-Rhino-Phalangeal Syndrome?

Answer 78

AD mutation of TRPS1 on 8q23.2.

Question 79

What is a common management strategy for Tricho-Rhino-Phalangeal Syndrome?

Answer 79

Growth hormone treatment, otoplasty, and rhinoplasty.

Question 80

What genetic mutation is responsible for TDO syndrome?

Answer 80

TDO syndrome is caused by autosomal dominant mutations in the DLX3 gene, which encodes the transcription factor homeobox protein DLX-3.

Question 81

What is the genetic etiology of oculo-dento-digital dysplasia (ODDD)?

Answer 81

ODDD is caused by autosomal dominant mutations in the GJA1 gene, which encodes connexin 43, a connexin protein of the intercellular junction.

Question 82

What are the three variants of tricho-rhino-phalangeal syndrome (TRPS)?

Answer 82

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).

Question 83

What skeletal features are associated with TDO syndrome?

Answer 83

Skeletal features include increased bone density of the long bones and skull, craniosynostosis, and dolichocephaly.

Question 84

What other skeletal abnormalities might be present in a patient with ODDD?

Answer 84

Other skeletal abnormalities include hyperostosis of the skull, broad ribs and clavicles, and abnormal trabeculation of the long bones.

Question 85

What skeletal features might be present in a patient with TRPS?

Answer 85

Short stature and hip malformations.

Question 86

What skeletal abnormalities might be present in a patient with oculo-dento-digital dysplasia (ODDD)?

Answer 86

Other skeletal abnormalities include hyperostosis of the skull, broad ribs and clavicles, and abnormal trabeculation of the long bones.

Question 87

What genetic mutation is associated with tricho-rhino-phalangeal syndrome (TRPS I)?

Answer 87

TRPS I is associated with autosomal dominant mutations in the TRPS1 gene on 8q23.2.

Question 88

What dental features are associated with tricho-dento-osseous (TDO) syndrome?

Answer 88

Dental features include enamel hypoplasia, hypocalcification, and taurodontism.

Question 89

What dental features might be present in a patient with oculo-dento-digital dysplasia (ODDD)?

Answer 89

Dental features include enamel hypoplasia, resulting in small, yellow, and friable teeth prone to decay.

Question 90

What variant of tricho-rhino-phalangeal syndrome (TRPS) is associated with multiple exostoses and intellectual disabilities?

Answer 90

This is TRPS II.