Random Dermatology MCQ - Bjornstad Syndrome

A 7-year-old boy presents with profound sensorineural hearing loss diagnosed in infancy. His mother notes his hair has always been extremely brittle, light-colored, and sparse, breaking off easily and leaving short, unruly tufts. On examination, you note the characteristic twisted appearance of the hair shafts under dermoscopy. What is the most likely underlying biochemical defect and the gene involved?

A. Defect in copper transport; ATP7A gene.
B. Defect in a mitochondrial aminoacyl-tRNA synthetase; BCS1L gene.
C. Defect in melanin synthesis; TYR gene.
D. Defect in desmosomal adhesion; DSP gene.
E. Defect in hair keratin; KRTHB1 gene.

Correct Answer: B. Defect in a mitochondrial aminoacyl-tRNA synthetase; BCS1L gene.

Answer and Explanation

The correct answer is B. This question describes Bjornstad syndrome, characterized by the combination of pili torti (twisted hair) and congenital sensorineural hearing loss. The hair finding is not just brittleness but the specific structural defect of pili torti, where the hair shaft is flattened and twisted 180 degrees on its axis. Bjornstad syndrome is caused by mutations in the BCS1L gene. This gene encodes a chaperone protein crucial for the assembly of Complex III in the mitochondrial respiratory chain, linking it to a mitochondrial dysfunction disorder. The BCS1L gene product is involved in energy metabolism, and its defect impacts tissues with high energy demands like the cochlea and hair matrix.

Why the Other Options are Incorrect:

• A. Defect in copper transport; ATP7A gene: This describes Menkes disease, which also features pili torti and neurological degeneration. However, Menkes disease is an X-linked disorder with severe progressive neurologic decline, connective tissue abnormalities, and very low serum copper, not isolated deafness.

• C. Defect in melanin synthesis; TYR gene: This causes oculocutaneous albinism, which features hypopigmentation of hair, skin, and eyes with visual abnormalities, not hair twisting or deafness.

• D. Defect in desmosomal adhesion; DSP gene: Desmoplakin mutations cause cardiocutaneous syndromes (e.g., Carvajal syndrome) with woolly hair, palmoplantar keratoderma, and cardiomyopathy, not pili torti and deafness.

• E. Defect in hair keratin; KRTHB1 gene: Defects in hair keratins cause disorders like monilethrix (beaded hair) or specific hair fragility, not the classic pili torti seen here.

Additional High-Yield Information for Exams:

• Clinical Features:

  • Hair (Pili Torti): Hair is brittle, sparse, light-colored (often silvery-blond), and short due to breakage. The twisting of the shaft can be seen under light microscopy or dermoscopy.

  • Hearing Loss: Congenital, bilateral, sensorineural hearing loss, which is non-progressive.

  • No Other Systemic Involvement: Unlike many other mitochondrial disorders, classic Bjornstad syndrome is typically isolated to hair and hearing, though some BCS1L mutations can cause more severe multi-system syndromes (e.g., GRACILE syndrome).

• Genetics: Autosomal recessive inheritance. Mutations in BCS1L are the cause. This gene is also mutated in more severe conditions like GRACILE syndrome (Growth Restriction, Aminoaciduria, Cholestasis, Iron overload, Lactic acidosis, and Early death) and Complex III deficiency, indicating a spectrum of severity.

• Pathogenesis: BCS1L is essential for the assembly of the Rieske iron-sulfur protein into mitochondrial Complex III (ubiquinol-cytochrome c reductase). Dysfunction of this respiratory chain complex impairs cellular energy (ATP) production, affecting highly metabolic tissues like the cochlear hair cells and the hair follicle matrix.

• Differential Diagnosis: The main differential is Menkes disease (X-linked, progressive neurological deterioration, low copper). Other causes of pili torti include isolated autosomal dominant pili torti, Crandall syndrome (pili torti, deafness, hypogonadism), and some ectodermal dysplasias.

• Associated Conditions & Prognosis:

  • Prognosis: For isolated Bjornstad syndrome, prognosis is excellent. The hair and hearing deficits are stable and non-life-threatening. The hair may improve slightly at puberty but rarely normalizes.

  • Spectrum of BCS1L Disorders: It is important to recognize that patients with Bjornstad syndrome should be evaluated for subtle signs of the more severe BCS1L-related syndromes (e.g., growth parameters, liver function, metabolic acidosis).

• Management & Rationale:

  • Rationale: Management is supportive and rehabilitative.

  • First-line:

    • Auditory: Early hearing aid fitting and auditory-verbal therapy. Cochlear implantation can be highly effective for severe hearing loss.

    • Dermatologic: Gentle hair care to minimize breakage. Avoid chemical treatments and heat styling. Hair may be kept short to manage appearance.

  • Monitoring: Baseline evaluation to rule out broader mitochondrial disease (e.g., growth assessment, neurologic exam, possibly lactic acid level). Regular audiologic follow-up.