Kocher–Debré–Semelaigne syndrome (KDSS) is

hypothyroidism Hypothyroidism is an endocrine disease in which the thyroid gland does not produce enough thyroid hormones. It can cause a number of symptoms, such as cold intolerance, poor ability to tolerate cold, fatigue, extreme fatigue, muscle aches, co ...

in infancy or childhood characterised by lower extremity or generalized muscular hypertrophy ( Herculean appearance), myxoedema,

short stature Short stature refers to a height of a human which is below typical. Whether a person is considered short depends on the context. Because of the lack of preciseness, there is often disagreement about the degree of shortness that should be called ...

, and

cognitive impairment Cognitive impairment is an inclusive term to describe any characteristic that acts as a barrier to the cognition process or different areas of cognition. Cognition, also known as cognitive function, refers to the mental processes of how a person ...

. The syndrome is named after

Emil Theodor Kocher Emil Theodor Kocher (25 August 1841 – 27 July 1917) was a Swiss physician and medical researcher who received the 1909 Nobel Prize in Physiology or Medicine for his work in the physiology, pathology and surgery of the thyroid. Among his many a ...

Robert Debré Robert Debré (7 December 1882 – 29 April 1978) was a French physician (pediatrician) at Necker-Enfants Malades Hospital in Paris. The largest pediatric hospital in Paris, the Robert-Debré Hospital - located in the North-East part of Paris ...

and Georges Semelaigne. Also known as Debré–Semelaigne syndrome or cretinism-muscular hypertrophy, hypothyroid myopathy, hypothyroidism-large muscle syndrome, hypothyreotic muscular hypertrophy in children, infantile myxoedema-muscular hypertrophy, myopathy-myxoedema syndrome, myxoedema-muscular hypertrophy syndrome, myxoedema-myotonic dystrophy syndrome. The adult-onset form of this syndrome is

Hoffmann syndrome Hoffmann syndrome is a rare form of hypothyroid myopathy and is not to be confused with Werdnig-Hoffmann disease (a type of spinal muscular atrophy). It was first documented in 1897 by Johann Hoffmann. It has adult-onset symptoms. It is compar ...

. Some sources claim that two of the differentiating symptoms between KDSS and Hoffmann syndrome is that Hoffmann syndrome lacks painful spasms and pseudomyotonia; however, this claim is in conflict with other sources that list these symptoms as also being present in Hoffmann syndrome.

Presentation

The age at which a child presents with KDSS may vary from new born to as late as 11 years of age. This disease is very rare as only less than 10% of children with hypothyroid myopathy develops this condition. Along with features of

(such as lethargy, slow heart rate, cold intolerance, dry skin, and hoarse voice) the main additional feature is muscle hypertrophy. It can happen in any muscle of the limbs, but commonly affects the calf muscles, giving the typical Herculean appearance. Other features are pseudo

myotonia Myotonia is a symptom of a small handful of certain neuromuscular disorders characterized by delayed relaxation (prolonged contraction) of the skeletal muscles after voluntary contraction or electrical stimulation, and the muscle shows an abnor ...

myokymia Myokymia is an involuntary, spontaneous, localized quivering of a few muscles, or bundles within a muscle, but which are insufficient to move a joint. One type is superior oblique myokymia. Myokymia is commonly used to describe an involuntary ey ...

, slow tendon reflex, slowed muscle contractions and relaxations, muscle stiffness, proximal muscle weakness and myopathy. The severity of these symptoms are determined by the period of hypothyroidism and the degree of deficiency of thyroid hormones. It may also include

macroglossia Macroglossia is the medical term for an unusually large tongue. Severe enlargement of the tongue can cause cosmetic and functional difficulties in speaking, eating, Dysphagia, swallowing and sleeping. Macroglossia is uncommon, and usually occurs ...

. EMG is either normal or may show myopathic low amplitude and short duration motor unit action potentials (MUAPS). The enzymes creatine kinase is elevated usually.

Pathophysiology

The assumed cause of muscle hypertrophy in KDSS is an abnormal metabolism of carbohydrates leading to increased glycogen accumulation and increased

mucopolysaccharide Glycosaminoglycans (GAGs) or mucopolysaccharides are long, linear polysaccharide Polysaccharides (), or polycarbohydrates, are the most abundant carbohydrates found in food. They are long-chain polymeric carbohydrates composed of monosacchari ...

deposits in the muscles. Yet another speculation is an excess intra cellular calcium due to ineffective reuptake into the sarcoplasmic reticulum, which causes a sustained contraction and thereby hypertrophy. In hypothyroidism the fast twitch muscle fiber is converted to slow twitch fiber, causing the slower reflex or hung up reflex. This may occur as a result of reduction in muscle mitochondrial oxidative capacity and beta-adrenergic receptors, as well as the induction of an insulin-resistant state, due to decrease in thyroid hormones. The causes for muscle weakness is said to be decrease in muscle

carnitine Carnitine is a quaternary ammonium compound involved in metabolism in most mammals, plants, and some bacteria. In support of energy metabolism, carnitine transports long-chain fatty acids from the cytosol into mitochondria to be oxidized for f ...

, decreased muscle oxidation, expression of a slower

ATPase ATPases (, Adenosine 5'-TriPhosphatase, adenylpyrophosphatase, ATP monophosphatase, triphosphatase, ATP hydrolase, adenosine triphosphatase) are a class of enzymes that catalyze the decomposition of ATP into ADP and a free phosphate ion or ...

in myosin chain and decreased transport across the cell membrane. The rigidity associated with congenital hypothyroidism may be due to abnormal development of basal ganglia.

Diagnosis

Differential diagnoses

Diseases known to have a

pseudoathletic appearance Pseudoathletic appearance is a medical sign meaning to have the false appearance of a well-trained athlete due to pathologic causes (disease or injury) instead of true athleticism. It is also referred to as a Herculean or bodybuilder-like ap ...

of the calves (

hypertrophy Hypertrophy is the increase in the volume of an organ or tissue due to the enlargement of its component cells. It is distinguished from hyperplasia, in which the cells remain approximately the same size but increase in number. Although hypertro ...

pseudohypertrophy Pseudohypertrophy, or false enlargement, is an increase in the size of an organ due to infiltration of a tissue not normally found in that organ. It is commonly applied to enlargement of a muscle due to infiltration of fat or connective tissue, ...

), including exercise intolerance and/or muscle weakness: *

(adult-onset hypothyroid myopathy), *

Glycogen storage disease A glycogen storage disease (GSD, also glycogenosis and dextrinosis) is a metabolic disorder caused by a deficiency of an enzyme or transport protein affecting glycogen synthesis, glycogen breakdown, or glycolysis, glucose breakdown, typically in m ...

(GSD-V, & late-onset GSD-II), * Non-dystrophic myotonias and pseudo

s (such as

Myotonia congenita ''Myotonia congenita'' is a congenital neuromuscular channelopathy that affects skeletal muscles (muscles used for movement). It is a genetic disorder. The hallmark of the disease is the failure of initiated contraction to terminate, often refe ...

and Brody disease), * Limb-girdle muscular dystrophy, * Duchenne and Becker muscular dystrophy * Focal

myositis Myositis is a rarely-encountered medical condition characterized by inflammation affecting the muscles. The manifestations of this condition may include skin issues, muscle weakness, and the potential involvement of other organs. Additionally ...

, * Sarcoid granulomas, and *

Amyloid Amyloids are aggregates of proteins characterised by a fibrillar morphology of typically 7–13 nm in diameter, a β-sheet secondary structure (known as cross-β) and ability to be stained by particular dyes, such as Congo red. In the human ...

deposits in muscles Thyroid metabolism can be disrupted secondary to a primary disease. A common

comorbidity In medicine, comorbidity refers to the simultaneous presence of two or more medical conditions in a patient; often co-occurring (that is, concomitant or concurrent) with a primary condition. It originates from the Latin term (meaning "sicknes ...

of the

metabolic myopathy Metabolic myopathies are myopathies that result from defects in biochemical metabolism that primarily affect muscle. They are generally genetic defects (inborn errors of metabolism) that interfere with the ability to create energy, causing a low A ...

McArdle disease (Glycogen storage disease type V) is hypothyroidism. It is also a comorbidity of late-onset Pompe disease (Glycogen storage disease type II). As both hyper- and hypothyroidism disrupts muscle glycogen metabolism, it is important to keep in mind differential diagnoses and their comorbidities when trying to determine whether signs and symptoms are either primary or secondary disease.

Treatment

The muscle hypertrophy and other symptoms are reversible on treatment with

levothyroxine Levothyroxine, also known as -thyroxine, is a synthetic form of the thyroid hormone thyroxine (T4). It is used to treat thyroid hormone deficiency (hypothyroidism), including a severe form known as myxedema coma. It may also be used to tre ...

References

{{DEFAULTSORT:Kocher-Debre-Semelaigne Syndrome Syndromes affecting the endocrine system Syndromes affecting stature Muscular disorders