CASE REPORT

Niger J Paed 2012;39 (2):79 – 83

Johnson A-W BR

Abdulkarim AA

Adedoyin O T

Adegboye A O

Amole A O D

Anhidrotic ectodermal dysplasia: a

case report in a Nigerian child and

literature review

DOI:http://dx.doi.org/10.4314/njp.v39i2.9

offensive nasal discharge; the skin

was thin, warm and dry; he had no

incisors and canines, but had a sin-

gle erupted premolar on either side

Received:16th December 2011

Accepted:3rd January 2012

Abstract This report of Hereditary

anhidrotic ectodermal dysplasia

(

HAED), a genetic disorder charac-

(

)

Abdulkarim AA

terized by abnormalities of struc-

tures of ectodermal origin, was in-

formed by its rarity, and its import

for survival in a tropical environ-

ment. The five-year old male was

first seen on account of inability to

cut the front teeth, and a persistent

offensive nasal discharge. He had

heat intolerance and inability to

perspire from early infancy. Pedi-

gree evaluation revealed that both

parents are Nigerians and unrelated,

but the maternal front dentition was

visibly defective. A 19-year old

female sibling needed dentures at

and

radiographic evidence of

Johnson A-W BR, Adedoyin O T,

Adegboye A O

Department of Paediatrics and

Child Health,

unerupted premolars was found.

Genetic counseling and parental

anticipatory guidance were offered,

as was antimicrobial treatment for

the co-morbid atrophic rhinitis.

Dentures were deferred on the den-

tist's advice.

This case report of HAED in a Ni-

gerian was aimed at raising the lo-

cal index of clinical suspicion by

highlighting the reality of rarities,

even with inadequate diagnostic

support. The diagnostic parameters,

literature review and the manage-

ment strategies are discussed.

Amole A O D

Department of Radiology

University of Ilorin Teaching

Hospital,

PMB1459 Ilorin, Nigeria.

E-mail : aishaakarim@yahoo.com

Tel: +2348033734509

1

0 years of age, while the father

was one of two survivors out of 12

children, eight of whom were

males. Findings included hy-

potrichosis;

Key words: Anhidrotic ectodermal

dysplasia; hypotrichosis; oligodon-

tia; Nigeria

“saddle-nose” deformity and an

mal glands and a mucosal defect affe_-₆cting the pharynx/

Introduction

1

upper respiratory tract respectively. Rarely, dysplastic

nails, hypoplastic₁_,₃m_,₅ammary glands and cornea have

Hereditary ectodermal dysplasia (HED) is a rare condi-

tion characterized by varying defects in the development

of structures derived from the_,₂ embryonic ectoderm,

been documented.

Against the background of the well known Darwinian

concept of “Survival of the fittest”, the evolutionary

import of a primary failure of sweating in the hot tropi-

cal environment is self-evident. Indeed, a conceivable

1

except those of the neural plate. The two major clinical

variants of HED are differentiated based on the presence

2

or otherwise of significant anhidrosis. Although auto-

“reverse” selection pressure may explain the rarity of the

somal dominant forms had been suggested in some pedi-

anhidrotic variety in the tropical environment.

grees, the mode of_-₆inheritance of HAED is frequently X-

1

linked recessive. Characteristic features include oli-

Furthermore, ubiquitous tropical childhood infections

with potentially life-threatening consequences like hy-

perpyrexia, complex febrile convulsion, heat stroke, and

brain damage may have_,c₆ontributed to the rarity of the

godontia involving the deciduous teeth (with few or no

permanent teeth), hypotrichosis, and paucity or absence

of the sweat glands with resultant severe thermoregula-

tory consequence(s)_-₅of anhidrosis, heat intolerance and/

3

1

disorder in the tropics. The current body of knowl-

or recurrent fever. Additionally, there is a fairly char-

edge on HAED is based largely on reports of Caucasians

living in the cooler temperate environment. Although

some of the earlier observations on this disorder ema-

nated from the Hindus, Tamils and Singhalese commu-

acteristic craniofacial appearance.

Conjunctivitis, chronic atrophic rhinitis, and hoarseness

constitute the clinical consequences of dysplastic lachry-

8

0

7

nities of the Asian subcontinent, to the best of the au-

ther questioning revealed that neither parent had heat

intolerance, inability to sweat or silky hair but the

mother's dentition was obviously defective with poor

gum anchorage and uneven spaces. She however never

required dentures and could not recall having a similar

delay in teeth eruption. Figure 1 summarizes the avail-

able data from the family study.

thors knowledge, only four reports in probands of Negro

ancestry exist in accessible English literature

5

,6,8,9

.

In a local report, the focus was on the oral manifesta-

tions and orthodontic manag₁₁ement, rather than the holis-

tic clinical characteristics. We report HAED in an

indigenous African as well as provide a critical review

of the diagnostic prerequisites of the disease.

Fig 1

Case report

The proband, SA (Reg. No. 195484) was a five-year old

male Nigerian, who was brought for consultation to the

University of Ilorin Teaching Hospital (UITH) by his 41

-

year old mother. The principal concern was the child's

inability to cut the front teeth at his age. The first set of

teeth were the upper pre-molars which did not appear

until age three years, and at presentation he had cut two

on either side of the upper and lower jaws. Further ques-

tioning revealed he had heat intolerance and suffered

from recurrent fever since birth with frequent afternoon

exacerbation during dry season. Furthermore, he has

never been noticed to perspire, even when the environ-

ment was hot. Over the years, parents have learnt to

maintain cooling outdoors with regular body sponging

using a towel soaked in cold water. At home, frequent

discomforts associated with heat intolerance have been

kept to a minimum by using air-conditioners. He had

thrice been hospitalized for febrile illnesses without any

specific causes found and these have coincided with

long periods of power outages and whenever he had to

stay outdoors for long periods during the hot dry season.

Key: A/W = Alive and Well

Proband's Mother

Proband's Father

Female, not alive

Male, not alive

F e m a l e ,

Male, alive

a l i v e

Other recurrent symptoms since early infancy included

stuffy nostrils frequently associated with foul smelling

nasal discharge, ozaena and occasional nighttime epi-

sodic cough.

#

Has defective dentition and/

or needed dentures

Divorce/Separated

The skin has been dry and scaly since birth, necessitat-

ing frequent change of expensive body cream and lo-

tions. Scalp hair has remained sparse, straight and silky

despite the absence of Fulani or Arab ancestry. Since he

was weaned at about the age of one year, feeds have

been restricted to pulverized foodstuffs, to obviate the

need for chewing. Although he was once registered at a

Nursery school at about the age of three years, the par-

ents have had to withdraw him from school because of

frequent paroxysms of pyrexia, jeers from older pupils

and “embarrassing stares” from teachers and other par-

ents.

Physical examination revealed an intelligent but rather

shy child with a satisfactory weight of 21kg, a normal

standing height of 109.5cm and a normal occipitofrontal

circumference of 51cm for the age. The upper to lower

body segment ratio was normal at 1.08:1. The tempera-

ture was 37.7oC in the air-conditioned consulting room.

The identifying physical findings of HAED are shown in

Figure 2 there was depression of the nasal bridge giving

a saddle appearance, the eye lashes were sparse, and the

eye brows were virtually absent. The palpebral fissures

are normal. His hair was straight, silky and scanty with

areas of visible scalp skin. The lips were moderately

everted and the skin (including the axillary area) was

thin and dry. Neither jaw contained incisors, canines or

molars (Figure 3A but four rather rudimentary and

shaky premolars, (one in each jaw on either side) was

evident. Other obvious abnormalities included periorbi-

tal darkening and pectus carinatum. There was no other

abnormality observed on systemic examination.

Family, Social and Pedigree History: The parents are

unrelated by blood and are of above-average socio-

economic status. The father is a career diplomat, while

the mother, a polytechnic graduate, has a successful

business outfit. The patient is the fourth of five chil-

dren. One of the older siblings, a 19 year old female,

required a set of orthodontic prosthesis following ab-

sence of the front teeth at the age of 11 years. She had

no other overt features of HAED but the skin has also

been relatively dry and rough from early childhood. Fur-

8

1

Fig 2

Investigations and Results

Radiograph of the jaws showed a few more un-erupted

buds of additional premolars (Figure 3B).

The thyroid function test results were within normal

limits; T3 was 1.3mg/ml (reference range: 0.8-2.1); T4

1

1.50 (international units/ml (reference range 0.2-5.0).

There were no facilities for DNA analysis. However,

extensive text reference coupled with the clinical find-

ings and pedigree data were consistent with those of the

rare HAED with a sex-linked pattern of inheritance. The

mother was intimated with the diagnosis and informed

about the likely mode of inheritance as well as the avail-

able therapeutic measures and preventive options. As at

the last clinic visit some eight months ago the child was

doing well except for the recurrent cold and heat intoler-

ance. He had still not cut additional teeth.

Fig 3A

Close-up views (lateral ) of the proband showing a

rather prominent forehead and saddle-like depression of

the nasal bridge, sparse/absent eye lashes and brows,

straight, silky and scanty hair, glossy skin, as well as the

moderately everted lips. A minimal deformity in the

upper pole of the auricle (pinna) is also evident (lateral

view).

Discussion and literature review

The earliest communicatio₃n on HAED was credited to

1

Darwin in his reference to Wedderburn's report in

1

838 of “...a Hindu family in Scinde, in which ten men,

in the course of four generations, were furnished in both

jaws taken together, with only four small and weak inci-

sor teeth, and with eight posterior molar.” That the dis-

order is inherited in an X-li₁n₄ked fashion, can be inferred

from Thunam's 1848 report of HAED in two first cous-

ins; a carrier state was correctly presumed in their com-

mon maternal grandmother. However, the current desig-

nation as hereditary ectodermal dysplasia of the an-

hidrotic type, reportedly pioneered by the 1929 clinico-

1

pathological expose of Weech was informed by the

need to distinguish it from the presumably more com-

mon hidrotic form, as well as the phenotypical mimicry

Fig 3A

of c₁o₅n_,₁g₆_,enital syphilis.

Clouston's subsequent re-

predicated on a long-term study of several

ports

1

4,15

constituted the earliest attempt at

families in Canada,

evolving an acceptable classification of the disease into

the presumably common hidrotic type with an auto-

somal dominant inheritance pattern, and the X-linked

anhidrotic variety. Clouston's view was corroborated₇ by

1

the subsequent observations of Williams and Fraser in

a study of several generations of Clouston's original

probands.

The discriminatory features, natural history, and man-

agement issues of the two major forms was the focus of

2

Fig 3B

a comprehensive review by Blattner. In a more recent

1

8

discussion of the subject, Frire-Maia and Pinheiro

Oral photograph (A) and a Lateral view of the skull ra-

diograph (B). Note “empty” anterior segment of the

gum, devoid of incisors and canines in the oral photo-

graph, and the radiographic evidence of rudimentary/

unerupted posterior teeth (3B). The peri-orbital linear

wrinkles are also evident in the oral photograph (Fig.

suggested there may indeed be over 121 varieties of the

condition with overlapping features.

There is a paucity of reports in black Africans and Afri-

cans in diaspora and the current report constitutes to the

best of our knowledge, the fifth report in a Negro fam-

ily, and perhaps the third in an indigenous black Afri-

3

A).

6

can. Familusi et al , had contended that despite the rar-

ity of this condition in blacks, the survival of the AED

8

2

mutant gene over the ages implies some unidentified

advantage of biological fitness in female carriers. The

recognition of the current case despite the investigative

limitations and the need for an early recognition and

appropriate treatment/domestic manipulation constitute

a few of the reasons for this report.

Whereas the hereditary basis of HAED had never been

in doubt, the possible patterns of inheritance remains

contentious. An X-linked recessive mode (EDA 1 muta-

tion) remains the most popular, but autosomal dominant

or recessive patterns (EDAR, EDARADD and

WNT1₁₅0_-₁A₉mutations) have been suggested in some pedi-

grees.

The current report in a male child could sug-

The clinician's acquaintance with the diagnostic parame-

ters is indispensable for early recognition of HAED. The

four characteristic features of HAED are identified as

anhidrosis or hypohidrosis, dental abnormalities, hy-

potrichosis, and the characteristic_,₁f₈acies all too well

gest the X-linked variant, however a recent report

showed that only the WNT10A mutation carriers dis-

played distinctive dental phenotypes and no facial dys-

morphism as is reported in the female members of the

index family.

2

demonstrated by the present case. Anodontia or oli-

godontia, obviously the most important parental concern

in this case, is undoubtedly a near-universal clinical

pointer of the disease and is demonstrated by the pre-

sent case in whom the oligodontia is fairly severe.

Whereas a presumptive diagnosis of EDA can be made

from the clinical parameters and pedigree study, investi-

gative strategies are aimed at confirming hypohidrosis

following a thermal stress, characterizing the oligodon-

tia, and as a prerequisite for a valid genetic counseling,

ascertaining the genetic basis of the disorder. The latter

involves detecting maternal carrier-state, and providing

prenatal diagnosis. Hypohidrosis may be confirmed by

demonstrating decreased or absent sweat pores in pal-

mar/finger tips' ridges, or the back (using the iodine-

starch test), after environmental heat exposure, or₄s_,₅u_,₇bcu-

taneous pilocarpine-induced (5mg) iontophoresis.

Autosomal dominant v₀ariant with variable penetrance

2

may also be an option. Due to the limitations in genetic

analysis, these cannot be further explored. There is cur-

rently no specific therapy for HAED, but given the com-

patibility with a normal life-span, parental genetic coun-

seling and anticipatory guidance particularly with re-

spect to temperature control and the related prevention

of febrile seizures an₄d brain damage constitute important

management issues.

In those with dysplastic or atrophic lachrymal glands,

synthetic tears may be required to forestall conjunctival

and corneal xerosis, while the ozaena associated with

atrophic rhinitis would benefit from periodic nasal irri-

gation and, as was carried out in this case, and antim-

4

icrobial therapy after appropriate microbiologic studies.

As was the case in an earlier local report, the provision

of dentures was deferred on the advice of the dentist till

an older age as it would forestall the need₁f₁or subse-

quent alteration and replacement with growth.

The consequence of the sweating-related thermo-

regulatory defect is more likely to provoke a search for

an infective aetiology, or an immune deficiency. Indeed,

in the current five-year old case, the parents had long

learnt to cope with this recurrent fever using simple

physical measures. Although we were unable to confirm

the extent of the sweating defect, hypohidrosis (as

against anhidrosis) is conceivably the more likely defect

in indigenous Africans. Also, the presence of features of

atrophic rhinitis in our proband (with a long-standing

mucopurulent nasal discharge) constitutes a clinical cor-

relate of the mucosal defect/atrophy associated with

HAED.

Conflict of interest: none

Funding: none

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