Ectodermal dysplasia

X

X

X

—

—

Rare

Hypohidrosis1

X

X

—

—

X

Nail dysplasia

X

X

Mild

X

Sparse hair

X

X

X

—

—

Tooth abnormalities

X

X

X

X

—

Cleft lip/palate

X

—

—

—

—

X

X

—

—

—

—

X Split-hand/foot malformation / syndactyly

X

X

X

X

X

Lacrimal duct obstruction

X

X

X

X

—

Dermal erosions

X

—

—

—

—

Hypopigmentation

X

X

X

—

—

Hypospadias

X

—

—

—

—

X

Trismus

X

Excessive freckling

X

Hypoplastic breasts

TGM5

ARAD

Skin erosions at birth

Erosions in AEC syndrome are typically more superficial not assoc w/formation of bullae.; Nondermatologic features dermatopathology also distinguish EBS from AEC syndrome. Autosomal recessive congenital ichthyosis

ABCA12 ALOX12B ALOXE3 CASP14 CERS3 CYP4F22 LIPN NIPAL4 PNPLA1 SDR9C7 SLC27A4

—

TGM1

AR

Erythroderma w/collodion membrane in newborn period1

AEC is not assoc w/collodion membrane or ichthyosis. Curly hair-ankyloblepharon-nail dysplasia syndrome (CHANDS)(OMIM 214350)

—

—

RIPK4

AR

Ankyloblepharon hair changes

CHANDS typically does not incl significant facial/oral clefting or skin erosions that are virtually universal in AEC syndrome. Cocoon syndrome2

—

—

CHUK

ARAD

Ankyloblepharon, cleft lip/palate, ectodermal dysplasia

Cocoon syndrome is assoc w/hypogammaglobulinemia recurrent infections (features not observed in AEC syndrome)

—

—

SHFM4

SHFM1(OMIM 183600)

—

—

—

—

DLX5

AD

Split-hand/foot malformation

SHFM1 is assoc w/high incidence of hearing loss.; Findings are largely restricted to limbs.

—

—

Dental lacrimal duct abnormalities are seen in 10% of persons.3 SHFM3(OMIM 246560)

10q24 contiguous gene duplication

AD

SHFM3 is not assoc w/lacrimal, dental, or ectodermal abnormalities (beyond nail abnormalities assoc w/developmental defects of the digits).4

—

—

SHFM6(OMIM 225300)

WNT10B5

AR

SHFM6 is not assoc w/lacrimal, dental, or ectodermal abnormalities.

—

—

TP63-related disorders generally

Hypohidrotic ectodermal dysplasia (HED)

EDA EDAR EDARADD

—

—

—

WNT10A

ADARXL

Hypotrichosis, hypohidrosis, hypodontia

Hypohidrosis in HED is severe enough to impair body temperature regulation, a problem not seen in TP63-related disorders.

—

—

Growth delay

Nutritional eval

Further assessment by gastroenterologist may be needed. Developmental

delay

Developmental assessment

Limb malformations

counseling

By genetics professionals1

To inform affected persons their families re nature, MOI, implications of a TP63-related disorder to facilitate medical personal decision making Family support/ resources

Treatment of Manifestations in Individuals with a TP63-Related Disorder Manifestation/Concern

Treatment

Considerations/Other

Ankyloblepharon filiforme adnatum

These strands of tissue between upper lower eyelids are often small autolyse shortly after birth; larger ones may require surgical separation by ophthalmologist.

—

Lacrimal duct atresia/obstruction

Possible need for probing or surgical intervention per ophthalmologist

—

Dry eyes / blepharitis

Hydrating ocular drops or gels

—

Skin erosions

Gentle wound care periodic, dilute bleach soaks (Dakins solution) to prevent secondary infection

Occlusive dressings should not be used, as they tend to stimulate granulation tissue. Treat secondary infections w/topical or oral antibiotics or antifungal agents when appropriate.

Sparse hair / alopecia

Wigs can be used as desired.

Hypodontia

Cleft lip/palate

Care managed by a multispecialty cleft team

—

Hearing loss

Myringotomy for conductive hearing loss from chronic otitis media

—

Breast/nipple asymmetry

Females: significant breast asymmetry may be corrected w/plastic surgery.

—

Growth delay

Optimization of oral caloric intake

Gastrostomy tube placement may be considered.

Developmental delay

Assessment treatment by developmental pediatrician /or child neuropsychologist

—

Limb malformations

OT hand/foot surgery as needed to optimize function

—

Psychological impact of phenotypic features

Referral for psychological support/counseling as necessary

OT = occupational therapy Surveillance Table 6.