Hypohidrotic ectodermal dysplasia — SAQ · MBBS SAQ

Question

15 marks15 min

Stem

A 14-month-old boy is brought in during summer with sparse fine scalp hair, dry skin, only two erupted conical teeth and recurrent unexplained temperature elevation. His maternal uncle had similar features. While waiting in a hot car park, the child becomes hot, lethargic and confused.[1][5]

Questions

a) Give the most likely diagnosis and classic triad. (2 marks) [1]

b) Explain the likely molecular pathway and inheritance, and name the minimum genes that a diagnostic panel should cover. (4 marks) [1]

c) State the immediate heat-emergency actions. (4 marks) [1][5]

d) Outline six long-term management domains. (3 marks) [1][2]

e) Give one discriminator each for Clouston syndrome and IKBKG-related ectodermal dysplasia with immunodeficiency. (2 marks) [3][4]

Model answer and marking guide

a) Diagnosis and triad — 2 marks

Hypohidrotic ectodermal dysplasia (HED): 0.5 mark.
Hypohidrosis or anhidrosis + hypotrichosis + hypodontia: 0.5 mark for each element.[1]

b) Pathway, inheritance and testing — 4 marks

Developmental pathway: EDA-A1 ligand → EDAR receptor → EDARADD adaptor → canonical NF-κB signalling for sweat-gland, hair-follicle and tooth development: 1.5 marks.
The pedigree makes EDA-related X-linked HED likely, but appearance alone does not establish inheritance: 0.5 mark.
A heterozygous mother can be variably manifesting because of X-chromosome inactivation: 0.5 mark.
Molecular testing should include EDA, EDAR, EDARADD and WNT10A at minimum; broader phenotype-directed ectodermal-dysplasia testing may be needed: 1 mark.
Cascade testing is offered after a familial pathogenic variant is identified: 0.5 mark.[1]

c) Heat emergency — 4 marks

Stop exertion, move to a cool environment and remove excess clothing: 1 mark.
Begin active external cooling with cool-water wetting or misting plus airflow; do not delay cooling while arranging care: 1 mark.
Call emergency services because confusion is a heat-stroke warning; continue cooling while help arrives: 1 mark.
Give cool oral fluid only if fully alert and swallowing safely; evaluate infection separately, and do not rely on antipyretics for environmental or exertional hyperthermia: 1 mark.[1][5]

d) Long-term care — 3 marks

Award 0.5 mark for any six, or equivalent well-explained domains:[1][2]

individual heat-avoidance and nursery/school/sport emergency plan;
paediatric dental/craniofacial review, preventive care and growth-adjusted removable prostheses;
genetics review and inheritance-specific reproductive counselling;
emollients and treatment of dermatitis or secondary infection;
ENT/hearing care for nasal concretions, otitis or sinus symptoms;
lubricating eye care and ophthalmology for persistent ocular symptoms;
respiratory assessment for chronic or recurrent symptoms;
nutrition, speech and psychosocial support.[1][2]

e) Two close look-alikes — 2 marks

Clouston (GJB6, autosomal dominant): sweating and teeth are usually preserved; marked nail dystrophy, alopecia and palmoplantar hyperkeratosis dominate: 1 mark.[3]
IKBKG-related EDA-ID: ectodermal features plus serious, unusual or opportunistic infection/immune dysfunction; it is not uncomplicated EDA-related XLHED: 1 mark.[4]

[1] [5]

References

[1]Wright JT, Grange DK, Fete M Hypohidrotic Ectodermal Dysplasia. GeneReviews, 1993.PMID 20301291
[2]Schnabl D, Grunert I, Schmuth M, et al. Prosthetic rehabilitation of patients with hypohidrotic ectodermal dysplasia: A systematic review. Journal of Oral Rehabilitation, 2018.PMID 29679503
[3]Mellerio J, Greenblatt D Hidrotic Ectodermal Dysplasia 2. GeneReviews, 1993.PMID 20301379
[4]Döffinger R, Smahi A, Bessia C, et al. X-linked anhidrotic ectodermal dysplasia with immunodeficiency is caused by impaired NF-kappaB signaling. Nature Genetics, 2001.PMID 11242109
[5]Eifling KP, Gaudio FG, Dumke C, et al. Wilderness Medical Society Clinical Practice Guidelines for the Prevention and Treatment of Heat Illness: 2024 Update. Wilderness & Environmental Medicine, 2024.PMID 38425235

Question

15 marks15 min

Stem

Questions

a) Give the most likely diagnosis and classic triad. (2 marks) [1]

b) Explain the likely molecular pathway and inheritance, and name the minimum genes that a diagnostic panel should cover. (4 marks) [1]

c) State the immediate heat-emergency actions. (4 marks) [1][5]

d) Outline six long-term management domains. (3 marks) [1][2]

e) Give one discriminator each for Clouston syndrome and IKBKG-related ectodermal dysplasia with immunodeficiency. (2 marks) [3][4]

Model answer and marking guide

a) Diagnosis and triad — 2 marks

Hypohidrotic ectodermal dysplasia (HED): 0.5 mark.
Hypohidrosis or anhidrosis + hypotrichosis + hypodontia: 0.5 mark for each element.[1]

b) Pathway, inheritance and testing — 4 marks

Developmental pathway: EDA-A1 ligand → EDAR receptor → EDARADD adaptor → canonical NF-κB signalling for sweat-gland, hair-follicle and tooth development: 1.5 marks.
The pedigree makes EDA-related X-linked HED likely, but appearance alone does not establish inheritance: 0.5 mark.
A heterozygous mother can be variably manifesting because of X-chromosome inactivation: 0.5 mark.
Molecular testing should include EDA, EDAR, EDARADD and WNT10A at minimum; broader phenotype-directed ectodermal-dysplasia testing may be needed: 1 mark.
Cascade testing is offered after a familial pathogenic variant is identified: 0.5 mark.[1]

c) Heat emergency — 4 marks

Stop exertion, move to a cool environment and remove excess clothing: 1 mark.
Begin active external cooling with cool-water wetting or misting plus airflow; do not delay cooling while arranging care: 1 mark.
Call emergency services because confusion is a heat-stroke warning; continue cooling while help arrives: 1 mark.
Give cool oral fluid only if fully alert and swallowing safely; evaluate infection separately, and do not rely on antipyretics for environmental or exertional hyperthermia: 1 mark.[1][5]

d) Long-term care — 3 marks

Award 0.5 mark for any six, or equivalent well-explained domains:[1][2]

individual heat-avoidance and nursery/school/sport emergency plan;
paediatric dental/craniofacial review, preventive care and growth-adjusted removable prostheses;
genetics review and inheritance-specific reproductive counselling;
emollients and treatment of dermatitis or secondary infection;
ENT/hearing care for nasal concretions, otitis or sinus symptoms;
lubricating eye care and ophthalmology for persistent ocular symptoms;
respiratory assessment for chronic or recurrent symptoms;
nutrition, speech and psychosocial support.[1][2]

e) Two close look-alikes — 2 marks

Clouston (GJB6, autosomal dominant): sweating and teeth are usually preserved; marked nail dystrophy, alopecia and palmoplantar hyperkeratosis dominate: 1 mark.[3]
IKBKG-related EDA-ID: ectodermal features plus serious, unusual or opportunistic infection/immune dysfunction; it is not uncomplicated EDA-related XLHED: 1 mark.[4]

[1] [5]

References

[1]Wright JT, Grange DK, Fete M Hypohidrotic Ectodermal Dysplasia. GeneReviews, 1993.PMID 20301291
[2]Schnabl D, Grunert I, Schmuth M, et al. Prosthetic rehabilitation of patients with hypohidrotic ectodermal dysplasia: A systematic review. Journal of Oral Rehabilitation, 2018.PMID 29679503
[3]Mellerio J, Greenblatt D Hidrotic Ectodermal Dysplasia 2. GeneReviews, 1993.PMID 20301379
[4]Döffinger R, Smahi A, Bessia C, et al. X-linked anhidrotic ectodermal dysplasia with immunodeficiency is caused by impaired NF-kappaB signaling. Nature Genetics, 2001.PMID 11242109
[5]Eifling KP, Gaudio FG, Dumke C, et al. Wilderness Medical Society Clinical Practice Guidelines for the Prevention and Treatment of Heat Illness: 2024 Update. Wilderness & Environmental Medicine, 2024.PMID 38425235