ectodermal dysplasia

ECTODERMAL DYSPLASIA

Dr. Yugandar

ectodermal dysplasias is of a group of inherited disorders

that share in common developmental abnormalities of two

or more of the following: hair, teeth, nails, sweat glands and

other ectodermal structures like

mammary gland, thyroid gland, thymus, anterior

pituitary, adrenal medulla, central nervous system, external

ear,melanocytes, cornea, conjunctiva, lacrimal gland and

lacrimal duct.

One definite benefit is that the problems encountered

by many patients and families are grouped regardless

of the specific subtype of ED &

Parents and children can benefit by being part of larger

support networks exemplified by the Ectodermal

Dysplasia Society

http://www.ectodermaldysplasia.org

the National Foundation for Ectodermal Dysplasias

http://www.nfed.org

Many conditions encompassed by this broad

definition are not usually considered as primarily ED

incontinentia pigmenti,

dyskeratosis congenita,

trichothiodystrophies,

Cardio facio cutaneous syndrome,

pachyonychia congenita & Goltz syndrome

By Definition they are ED, but

common practice has been to consider many of these as

separate entities

’

The first clinical cases with features of ED were reported as early

as 1792, when Danz described two Jewish boys with congenital

absence of hair and teeth

In 1875 Charles Darwin reported the case communicated to

him by a Mr. Wedderburn,

Hindoo family in Scinde in which ten men, in the course of four

generations, in their both jaws taken together, with only four

small and weak incisor teeth and with eight posterior molars

This family would have X-linked hypohidrotic ectodermal

dysplasia

small series of cases with hypotrichosis, hypodontia,

onychodysplasia and anhidrosis

had been described under various names such as

dystrophy of hair and nails

imperfect development of skin, hair and teeth

congenital ectodermal defect

term ‘ectodermal dysplasia’ appear 1929

Touraine suggested ‘ectodermal polydysplasia’

Weech specified three essential aspects of ectodermal

dysplasias:

most of the disturbances must affect tissues of

ectodermal origin

these disturbances must be developmental

heredity plays a causal role

ECTODERM Ectoderm is one of the three primary germ cell layers in the

very early embryo

The other two layers are the mesoderm (middle layer) and

endoderm , with the ectoderm as the most exterior layer

It emerges and originates from the outer layer of germ cells

The word ectoderm comes from the Greek ektos meaning

"outside", and derma, meaning "skin."

Ectoderm differentiates to form

the nervous system (spine, peripheral nerves and brain),

tooth enamel and the epidermis

It also forms the lining of mouth, anus, nostrils, sweat

glands, hair and nails

In vertebrates, the ectoderm has three parts: external

ectoderm (also known as surface ectoderm), the neural

crest, and neural tube

the latter two are known as neuroectoderm

1.Pre aortic ganglion

2.Sympathetic ganglion

3.Organ plexus 4.Suprarenal gland 5.Dorsal root

ganglion 6.Surface ectoderm 7.Neural tube 8.Dorsal aorta 9.Urogenital ridge 10.Notochord

What is the cause of ectodermal dysplasia?

mutation or deletion of certain genes located on different

chromosomes.

ED s are caused by a genetic defect they may be inherited

or passed on down the family line.

In some cases, they can occur in people without a family

history of the condition, in which case a de novo mutation

has occurred.

Connexin defects :

Gap junctions are intercellular channels that connect the

cytoplasm of neighbouring cells,

Facilitating cellular growth, differentiation,tissue

morphogenesis, homeostasis

Transmembrane connexin proteins undergo

oligomerization to form the connexons that compose Gap

junctions

In the Golgi network

six connexin subunits assemble

to form a connexon

The connexon is then

transported to the plasma

membrane.

Other connexons then

coaggregate to form

homotypic or heterotypic gap

junctions.

Cx26, Cx30, Cx31 and Cx43 expressed in ectoderm-

derived epithelia of the inner ear and cornea as well as in

the epidermis and its appendages

Connexin defects a/f the sensorineural deafness, keratitis

and cutaneous abnormalities (ranging from keratoderma

to erythro keratoderma to ectodermal dysplasias

affecting the hair and nails)

Genetics 

Are the ectodermal dysplasias hereditary?

The ED are caused by alterations in genes

Altered genes may be inherited from a parent

Normal genes may become altered (mutate) at the time of

egg or sperm formation or after fertilization

Chances for parents to have affected children depend on the

inheritance pattern of the type of ectodermal dysplasia

How Inheritance Works New Mutation:

Generally, when a mutation has occurred, there is little chance

that it will occur in another child of the same parents

The affected child may transmit the trait

Autosomal Dominant :

When the ED is an autosomal dominant trait, the parent

who is affected has a single copy of the abnormal gene and

may pass it on to his or her children

Regardless of the gender of the parent or the child, there is

a 50% chance for each child

All children who receive the abnormal gene will be

affected

Autosomal Recessive

When the ectodermal dysplasia in the family is an autosomal

recessive trait, the usual situation is that each parent is unaffected

The parents are said to be carriers

They each have a single copy of the abnormal gene

the chance for them to have another affected child is 1 in 4

1 in 4 children get a copy of the abnormal gene from each

parent and is affected

2 in 4 gets only one copy each and are carriers

the remaining 1 in 4 inherits a normal gene from each parent

and is not affected

X-Linked Recessive If a woman is a carrier of an X-linked recessive

disorder there is a 50% chance that each male child

will receive the abnormal gene and be affected 50% chance that each female will receive the

abnormal gene and be a carrier (like the mother). 

If a man has the abnormal gene he is affected and will pass the gene on to all

of his daughters. The daughters will be carriers Since the gene is on the X chromosome, sons

will not be affected because they receive the mans Y chromosome

Freire-Maia and Pinheiro classification depend on clinical

phenotypes

& inheritance patterns of ED

designated conditions by groups depending on presence

of hair, nail, tooth or sweat gland abnormalities

conditions that had involvement of

hair (1), teeth (2), nails (3) ,sweat glands (4),other

ectodermal (5)

Classification: molecular approaches

Plays important insights into the molecular basis of

the ED

the molecular data have confirmed clinical

impressions,

Eg: Hay–Wells syndrome and

ectrodactyly, ectodermal dysplasia,

clefting (EEC) syndrome

Classification: Genetic mechanisms

ED due to mutations in tumour necrosis factor

(TNF)-like/NF-κB signalling pathways,

the p63-related ED

ED due to other transcription factors

ED due to mutations in gap junction proteins.

In an attempt to classify these, different subgroups

are created according to the presence or absence of

4 primary ED defects:

ED1: Trichodysplasia (hair dysplasia)

ED2: Dental dysplasia

ED3: Onychodysplasia (nail dysplasia)

ED4: Dyshidrosis (sweat gland dysplasia)

Eds are categorised into one of the following subgroups made up from the primary ED defects

Subgroup 1-2-3-4 Subgroup 1-2-3 Subgroup 1-2-4 Subgroup 1-2 Subgroup 1-3 Subgroup 1-4 Subgroup 2-3-4 Subgroup 2-3 Subgroup 2-4 Subgroup 3 Subgroup 4

In 2001, Priolo and Laganà reclassified the ectodermal

dysplasias into 2 main functional groups:

(1) defects in developmental regulation/epithelial-

mesenchymal interaction

(2) defects in cytoskeleton maintenance and cell stability.

In 2003, Lamartine reclassified ED into the following 4

functional groups based on the underlying pathophysiologic

defect:

(1) cell-to-cell communication and signaling

(2) adhesion

(3) development

(4) other

The most common ectodermal dysplasias

Hypohidrotic ED which falls under subgroup 1-2-3-4

Hidrotic ED which comes under subgroup 1-2-3.

The three most recognised ED syndromes fall into the

subgroup 1-2-3-4

they show features from all four of the primary ED

defects 

Ectrodactyly-ED-clefting syndrome

Rapp-Hodgkin hypohidrotic ED

Ankyloblepharon, ectodermal defects, cleft lip/palate

(AEC) or Hay-Wells syndrome

Hypohidroticectodermal dysplasia

X-linked HED is the most common of ED

Charles Darwin described it first,Later by Christ,

Siemens & Touraine

characterized by

o hypotrichosis

o hypodontia,

o hypohidrosis

Majority are X-L-R inheritance

involved gene ED- 1,located on Ch X-q12-13.1.

Encodes a protien ECTODYSPLASIN A ,member of

TNF family

AD & AR inheritance can occur

Autosomal gene has been mapped to Ch 2q 11-q1

(ED 3 )

CRINKLED gene identified – AR HED

Autosomal recessive HED is clinically identical to

X-linked HED

females are as severely affected as males

PATHOPHYSILOGY :

Mutations in the EDA, EDAR, and EDARADD genes

cause HED

The EDA, EDAR & EDARADD genes provide

instructions for making proteins

These proteins form part of a signaling pathway that is

critical for the interaction between two cell layers, the

ectoderm and the mesoderm

CLINICAL FEATURES

Hair:

Scalp hair is sparse, fine, lightly pigmented and grows

slowly

Eyebrows & eyelashes are scanty or absent

Secondary sexual hair in the beard, pubic and

axillary regions is variably present and may be normal

Hair on the torso and extremities is usually absent

Teeth:

Both deciduous and permanent teeth are affected

The alveolar ridges are hypoplastic

missing teeth or retarded growth of teeth

peg-shaped

Tooth enamel is also defective

Dental treatment is necessary & children as young as 2

years may need dentures

Conical teeth

• Upper Incisors have been resorted• Orthopantogram shows absence of 10 Primary & 11 Permanent teeth

Nails : Nails are normal in most individuals

Sweat glands:

Sweating is severely diminished or absent due to a

paucity or absence of eccrine glands

An absence of sweating leads to an inability to

thermoregulate

Thermoregulation is most problematic in infants and

young children, may recurrent bouts of fever as high as

42°C

Heat intolerance can occur in older children and adults

Skin:

At birth, affected males may demonstrate marked

scaling or peeling of their skin

skin is fine, smooth and dry in adults

Peri orbital hyperpigmentation

fine wrinkling around the eyes

Eczema is common and is prominent in flexural areas

Small milia like papules may be found on the face

Diminished or absent salivary

glands & mucous glands of the nose, mouth and ears cause

nasal obstruction by thick, fetid nasal discharge &

adherent nasal crusts, sinusitis

recurrent upper respiratory tract infections

Diminished production of tear film

from the lacrimal glands cause dry eyes, photophobia &

corneal damage

affected males have abnormalities of the nipples

including absent, simple or accessory nipples

feeding problems in infancy

xerostomia,hoarse voice & impacted cerumen

Craniofacial features:

Distinctive facies with frontal bossing, concave midface,

saddle nose and everted lips

30% of affected males have small ears

facial features may not be obvious at birth, but become

more noticeable with age

HistoPathology:

The epidermis is thin with effacement of rete ridges.

Hair follicles and sebaceous glands, Apocrine glands are

variably reduced

Mucous glands of the upper respiratory tract may be sparse

Light and scanning electron microscope findings of

hair shaft abnormalities are longitudinal clefts or

grooves and transverse fissuring,bulb of the hair

shaft is dystrophic

Mandible X-ray show Dental hypoplasia or aplasia

Epidermal & follicular orthokeratotic

hyperkeratosis

Arrector Pili muscle oriented parallel to skin surface

Apocrine ducts enter follicles at abnormal locations

Comedo formation

Prognosis:

Failure to thrive occurs in up to 40% of affected males

Height and weight are compromised in early childhood but

appear to normalize with time.

Mortality in infancy and early childhood is historically 25%

Due to hyper thermia, failure to thrive and respiratory

infections

Diagnosis

Associated Hyperthermia desreves in early diagnosis in

childhood

Careful clinical examination

Standard methods for Sweat production & Sweat pore

counts by Silicone rubber plastic imprints,Starch – Iodine

test,Pilocarpine iontophoresis,Valerio Ventruto Tech

( Palmar finger tip Sweat pore counting )

Skin biopsy :

absence or sparse sweat glands in dermis of hypothenar

area

decrease no of sebaceous glands & hair follicles in other

areas

Mortality/Morbidity:

related to the absence or dysfunction of eccrine and

mucous glands.

Intermittent hyperpyrexia may occur in infants with

decreased sweating.

The mortality rate approaches 30%. Recurrent high

fever may also lead to seizures and neurological

sequelae

Pharyngitis, rhinitis, cheilitis

dysphagia may result from reduced numbers of

functional mucous glands in the respiratory and

gastrointestinal tracts.

Growth failure is common.

What is the treatment for ectodermal dysplasia?

No specific treatment for ectodermal dysplasia

Management of ED is by treating the various symptoms

Patients often need to be treated by a team of doctors and

dentists, rather than a sole practitioner

abnormal or no sweat gland function should live in cooler

climates or in places with air conditioning at home, school

and work.

Artificial tears can be used to prevent damage to the

cornea in patients with defective tear production

Saline irrigation of the nasal mucosa may help to

remove purulent debris and prevent infection

Early dental evaluation and intervention is essential

Surgical procedures such as repairing a cleft palate may

lessen facial deformities and improve speech.

Research on Gene correction or administration of

recombinant EDA protein. Proof of principle has been

achieved in a dog model for this approach

Psychological support for affected children

Prevention :

Prenatal Diagnosis by fetal skin biopsy possible after 24

weeks of gestation ( Sweat gland start to develop )

Glands may be shriveled or absent

DNA probing tech on Chorionic Villus Biopsy

Differential Diagnosis

infants with scaling skin may be misdiagnosed as

collodion babies with lamellar ichthyosis

Basan syndrome is characterized by

hypotrichosis, hypodontia and hypohidrosis, but also by

severe nail dystrophy and congenital absence of

dermatoglyphics

Differential Diagnosis:

Alopecia Areata

Aplasia Cutis

Congenita Focal Dermal Hypoplasia Syndrome

Incontinentia Pigmenti

Naegeli- Franceschetti-Jadassohn Syndrome

Pachyonychia Congenita

Hidrotic Ectodermal Dysplasia ( Cloustons Syndrome )

Palmoplantar keratoderma

Hypotrichosis

Nail dystrophy

Genetics :

AD pattern,ED 2,

Ch 13q11-q12.1,member of Gap jn family connexin- 30

Clinical features :

Nail dystrophy –MC,short discolored, thickened

with striations are seen over bulbous finger tips

Scalp hair: thin,brittle,normal at birth gradually hair loss &

total alopecia

Axillary & Pubic hair are vellus or sparse or absent

Diffuse palmoplantar keratoderma with deep fissuring

Sweating is normal

Skin thickening beneath free edges of nails,finger

joints,knuckles

Thickening of skull bones,tufting of terminal

phalanges of fingers and nails

Oral leukoplakia may be seen

Teeth may be normal,prone to Early Caries

Syndactylyl & Polydactylyl

Mental & Physical Retardation

Diagnosis :

Palmoplantar Keratoderma

normal facies, normal sweating & teeth differentiate .

Prognosis:

Life expectancy will be normal

Persistent Malodourous Onychomycosis

Squamous cell carcinoma of nail bed

Management:

Keratolytic agents & Emollients for PPK

Systemic Retinoids

Ectrodactylyl-Ectodermal Dysplasia-Cleft Lip ( EEC Syndrome)

Very Rare, Both Mesodermal & Ectodermal structures

Described by COCKAYNE in 1936

3 types:

EEC 1,

EEC 2,

EEC 3

GENETICS :

AD pattern

Mutation of P 63 gene ( similar to P53) located on Ch

7q11.2-q21.3

P63 is critical to maintain Progenitor cells responsible

for Genesis of Limbs & Cranio facial regions in fetal

life

Clinical features:

Lobster claw deformity: Split hand & foot – MC

3rd & 4th Digits - MC

Tetramelic involvement –MC

Nails Hypoplastic & Dystrophic

Cleft Palate & Lip

Typical face : Hypoplastic Maxillae, Short

Philtrum, Broad Nasal tip

Oligodontia & Anodontia

Hair: Sparse,dry,scalp dermatitis

MR, hamartoma of tongue, hydronephrosis

Diagnosis

MAJOR MINOR

ED

Ectodactyly

Cleft Palate/Lip

Lacrimal duct abnor.

Renal Anomolies

Deafness

MR

Choanal atresis

X – Ray of deformed hand show absence or hypoplasia of Meta carpals & Metatarsals

Prognosis :

Corneal Scarring & Blindness due to Recurrent Keratitis

Treatment :

Repair of Cleft palate & Lip

Multi disciplinary approach for other abnormalities

Prevention :

Cleft Lip/Palate – Prenatally by USG

Rapp-Hodgkin Syndrome/Hay-Wells Syndrome ( AEC Syndrome )

Genetics :

AD Pattern

Missense Mutation in SAM domain of P63

cleft lip/palate

hypotrichosis, hypodontia,

absent or dystrophic nails ,mild hypohidrosis

One distinctive feature is ankylo blepharon filiforme

adnatum—partial thickness fusion of the eyelid margins

severe scalp erosions

Scalp dermatitis with erosions may result in scarring alopecia

CLINICAL FEATURES :

Babies at birth have Erythroderma – MC

Peeling, red, parchment-like skin in a newborn parchment skin resolves over the first few

weeks of life and the underlying skin is dry

Marked hypohidrosis – heat intolerance

Hair is sparse, pale with STEEL WOOL Texture

Hair shaft abnormalities – PILI TORTI

Nail dystrophy, Cleft palate /Lip

• Abnormal hair shaft showing PILI TORTI & Longitudinal groove ( PILI CANALICULI )

Hands of son and father showing brittle,thin & dystrophic nails

Face : Frontal bossing ,maxillary hyperplasia

narrow nose, broad nasal bridge & small mouth

Fusion of EYE LIDS most distinc feature

Hypodontia or Conical Teeth

VSD

Syndactylyl,

Treatement :

Surgical correction of eye lids

Correction of Hyperhidrosis

Johanson-Blizzard Syndrome

AR inheritance

Cong. Membranous aplasia cutis of scalp

Deafness,Dwarfism

MR,Hypotonia

Genital abnormalities

DM,Hypothyroidism

Schopf-Schultz-Passarge Syndrome

AR inheritance

Cysts at eyelid margins

Palmo plantar keratoderma

Hypotrichosis

Hypodontia

Benign & Malignant tumors of Palms & Soles

Syndromes with ectodermal dysplasia•

Berlin syndrome : Generalized grayish-brown

hyperpigmentation with Sparse eyebrows with absent

lateral aspect, delayed dentition/hypodontia, short

stature, sexual underdevelopment in male patients,

mental retardation

Described in one family (Iranians living in Israel; four

affected siblings; consanguineous parents)

Lucky/Winter syndrome

Generalized hyperpigmentation with guttate

Scant lightly pigmented hair, enamel hypoplasia (single

central incisor in one patient), Likely autosomal dominant

inheritance

Acromelanosis albo-punctata syndrome

Diffuse hyperpigmentation with atrophic skin guttate on

the dorsal aspects of the hands and feet

Keratotic follicular papules on the legs

pili torti

platonychia

Nails Hair Teeth Sweat gland others

HYPOHIDROTIC ED

Gen Normal

Dry,hypochromic & hypotrichosis of scalpMoustache & Beard - NormalEye brow & Lashes - absent

Hypodontia

Peg shaped incisors / canines

Dec Epidermal ridge sweat pores

Skin –thin,dry - abs sebaceous glFace: Saddle nose,frontal bossingPharyngitis LaryngitisAplasia of Breast

HIDROTIC ED

Thickened/ discoloured,clubbing

Dry,Slow Growing, Eye brow/ Lashes- Scanty or abs

Occ Anodontia/ hypodontia,caries

Normal Skin-Dry,scalyThick dyskeratotic palms & solesTufting of terminal Phalanges,myopia

EEC ED Thin,pitted,striated nails

Hypotrichosis of scalp,bodyEye brow/Lashes - abs

Ano/hypo/micro dontia

Occasionally hypohidrosis without hyperthermia

Palmoplantar hyperkeratosis,cleft lip/palat,speckled iris,syndactylyl,ectrodatylyl,clinodactylyl,

AEC Sever dystrophy

HypotrichosisSteel wool texturePILI TORTIPILI CANALICULI

Sever hypodontia

Hypohidrosis but no hyperthermia

Dry smooth,pp hyperkeratosis,dermatoglyphic patter- abs,Scalp pustulation

No / Severely reduced sweating

Sev Immune defect

• HED/IM

No Immune eff.

• X-LR HED• AD- HED• AR-HED

Normal/mild dec sweating

Normal teeth

• Clouston• ED/skin

fragility

Abnormal teeth

No facial cleft

• Tooth & nail

/witkop•

Trichodentoosseous

Facial cleft

Limb abnormality +• EEC

• Margarita island ED• Limb-mammary

Limb abnormality – • AEC

• Rapp- Hodgkin ED

One well known person with ED is Actor Michael Berrymen

Famous Skate boarder & artist Levi Hawken,well known with Nek Minit Videos on you tube

Thank You Very Much

Thank you