Kocher–Debre–Semelaigne syndrome

Overview

Kocher–Debré–Semelaigne syndrome (KDS) is a rare pediatric endocrine disorder characterized by muscular pseudohypertrophy (enlargement of muscles without true muscle strength increase) in association with longstanding hypothyroidism. First described in the early 20th century, the syndrome is most commonly observed in children with untreated or severe hypothyroidism. Affected children may appear muscular and strong due to the swollen muscles, particularly in the calves, but actually exhibit muscle weakness and developmental delays.

Causes

Kocher–Debré–Semelaigne syndrome is caused by prolonged, untreated hypothyroidism in early childhood. Hypothyroidism may result from:

• Congenital hypothyroidism (due to thyroid dysgenesis or dyshormonogenesis)

• Autoimmune thyroiditis (e.g., Hashimoto's thyroiditis)

• Iodine deficiency or other acquired causes

The syndrome arises due to the effects of thyroid hormone deficiency on muscle metabolism and overall growth and development. Accumulation of mucopolysaccharides and other substances in the muscles leads to their enlargement and stiffness.

Symptoms

Children with Kocher–Debré–Semelaigne syndrome typically exhibit the following features:

• Muscular pseudohypertrophy, especially in the calves, thighs, shoulders, and tongue

• Generalized muscle weakness and stiffness

• Delayed motor milestones

• Short stature and growth retardation

• Bradycardia (slow heart rate)

• Constipation

• Dry, coarse skin and hair

• Fatigue and lethargy

• Delayed mental and physical development

• Hoarseness of voice and facial puffiness

The muscle enlargement may give a misleading appearance of athletic build, despite the underlying weakness.

Diagnosis

Diagnosis of Kocher–Debré–Semelaigne syndrome is based on clinical features and laboratory confirmation of hypothyroidism. Diagnostic steps include:

• Thyroid function tests: Elevated TSH and low free T4 levels confirm hypothyroidism

• Serum creatine kinase (CK): May be elevated due to muscle involvement

• Electromyography (EMG): To assess muscle function (shows myopathic changes)

• Muscle biopsy: Rarely required but shows muscle fiber hypertrophy with mucopolysaccharide accumulation

• Bone age assessment: Often delayed in affected children

Early recognition is essential to initiate treatment and prevent long-term complications.

Treatment

The mainstay of treatment for Kocher–Debré–Semelaigne syndrome is thyroid hormone replacement. Key aspects of management include:

• Levothyroxine therapy: Daily oral thyroid hormone replacement to normalize thyroid levels

• Monitoring thyroid function: Regular blood tests to adjust medication dosage and maintain hormonal balance

• Physical therapy: To improve muscle strength and coordination

• Nutritional support: In cases of growth failure or feeding difficulties

Early and consistent treatment leads to significant improvement in symptoms and reversal of most clinical features.

Prognosis

With early diagnosis and proper thyroid hormone replacement, the prognosis for Kocher–Debré–Semelaigne syndrome is excellent. Muscle pseudohypertrophy and weakness typically resolve over time, and growth and developmental progress improve significantly. Delayed diagnosis, however, can result in persistent growth retardation, cognitive impairment, and irreversible musculoskeletal changes. Lifelong follow-up is necessary to ensure optimal thyroid function and normal development.