ectodermal dysplasia
TRANSCRIPT
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