Random Dermatology MCQ - Ectodermal dysplasia

A 6-month-old male infant is brought in due to frequent high fevers, especially in warm weather. On examination, he has very sparse, fine scalp hair, eyebrows, and eyelashes. He is missing several primary teeth, and those present are conical in shape. His skin is dry and finely wrinkled, particularly around the eyes. The mother reports he rarely sweats and becomes irritable and hot with minimal activity. What is the most likely mode of inheritance and the underlying pathological mechanism of this condition?

A. Autosomal dominant; defect in connexin proteins.
B. X-linked recessive; defective ectodysplasin A signaling (EDA pathway).
C. Autosomal recessive; defect in hair keratin.
D. Mitochondrial; defect in oxidative phosphorylation.
E. Sporadic; postzygotic mutation.

Correct Answer: B. X-linked recessive; defective ectodysplasin A signaling (EDA pathway).

Answer and Explanation

The correct answer is B. This question describes the classic presentation of X-linked hypohidrotic ectodermal dysplasia (HED), the most common form of ectodermal dysplasia. The triad is: hypohidrosis (greatly reduced ability to sweat, leading to febrile episodes), hypotrichosis (sparse, fine hair), and hypodontia (missing and/or malformed teeth). The male gender and severe presentation are typical for an X-linked disorder. The underlying defect is in the EDA/EDAR/NF-κB signaling pathway, which is critical for the development of ectodermal appendages. Mutations in the EDA gene, which encodes ectodysplasin A, are the most common cause.

Why the Other Options are Incorrect:

• A. Autosomal dominant; defect in connexin proteins: This describes other forms of ectodermal dysplasia, such as Clouston syndrome (hidrotic ectodermal dysplasia due to GJB6 mutations), which features severe nail dystrophy and normal sweating.

• C. Autosomal recessive; defect in hair keratin: Isolated hair keratin defects cause specific hair shaft disorders (e.g., monilethrix), not the triad of hypohidrosis, hypotrichosis, and hypodontia seen here.

• D. Mitochondrial: Mitochondrial disorders present with progressive multisystem involvement (myopathy, encephalopathy, lactic acidosis), not this specific, stable triad of ectodermal defects.

• E. Sporadic: While de novo mutations can occur, the classic clinical picture and inheritance pattern for this presentation is X-linked recessive.

Additional High-Yield Information for Exams:

• Pathogenesis: The EDA pathway is essential for epithelial-mesenchymal interactions during the formation of hair follicles, sweat glands, and teeth. Disruption leads to the characteristic features.

• Clinical Features:

  • Hypohidrosis/Anhidrosis: The most dangerous feature. Inability to sweat leads to hyperthermia, fevers of unknown origin, and heat intolerance.

  • Hypotrichosis: Scalp and body hair is fine, sparse, slow-growing, and lightly pigmented.

  • Hypodontia/Oligodontia: Teeth are often absent (most commonly lateral incisors, premolars) or peg-shaped/conical.

  • Facies: Characteristic facial features include a depressed nasal bridge, prominent forehead, thick lips, and periorbital wrinkling.

  • Other: Dry skin (xerosis), increased respiratory infections (due to defective mucous glands), and atopy.

• Differential Diagnosis: The main differential is between X-linked HED and autosomal forms of HED (due to EDAR or EDARADD mutations), which can affect both males and females. Other ectodermal dysplasias like Clouston syndrome (normal sweating, nail dystrophy) and Rapp-Hodgkin syndrome (cleft lip/palate) are distinguished by additional features.

• Associated Conditions & Prognosis:

  • Prognosis: With proper management, life expectancy is normal. The main risks are hyperthermic crises in infancy/childhood and complications from recurrent respiratory infections.

  • Immunodeficiency: Some forms, especially those associated with IKBKG/NEMO mutations, are combined with significant immune deficiency (HED with immune deficiency).

• Management & Rationale:

  • Rationale: Management is preventive and supportive, focusing on temperature regulation, dental rehabilitation, and managing complications.

  • First-line/Critical Measures:

    • Temperature Control: Educate family on strict avoidance of overheating. Use cooling vests, air conditioning, and frequent cool baths.

    • Dental Care: Early pedodontic and prosthodontic intervention is crucial. Dentures or dental implants are often needed for function, speech, and facial development.

  • Other Management: Artificial tears for dry eyes, emollients for dry skin, and aggressive treatment of respiratory infections. Genetic counseling for the family.

  • Emerging Therapy: Ectodysplasin A replacement therapy (protein substitution) has shown promise in clinical trials to improve symptoms.