Postgraduate Medical Journal (May 1982) 58, 307-3 10

Kocher-Debre-Semelaigne syndrome and congenital nystagmus

K. RADHAKRISHNANtM.D., D.M., M.A.M.S.

B. N. S. WALIA*M.D., D.C.H., M.A.M.S.

K. VENKATESWARLU*M.B.B.S.

S. B. S. MANN:M.S.

Departments of tNeurology, *Paediatrics and tOtorhinolaryngologyPostgraduate Institute of Medical Education and Research, Chandigarh-160012, India

SummaryA 11-year-old boy with hypothyroidism developedgeneralized muscle hypertrophy and proximal muscularweakness. Electromyographic findings were suggestiveof myopathy. He had had congenital nystagmus (CN)since early infancy. Although the association of child-hood hypothyroidism and CN has been documentedbefore, the triad of hypothyroidism, hypertrophicmyopathy and CN exhibited by the patient is believedto be unique.

IntroductionThe uncommon association of muscle hyper-

trophy with childhood hypothyroidism has beenreferred to as the Kocher-Debre-Se'mlaigne (KDS)syndrome (Najjar and Nachmann, 1965; Spiro et al.,1970). Congenital nystagmus (CN) is an ocularmovement disorder apparent at birth or shortlythereafter, characterized by bilateral pendular orjerk nystagmus with an eccentric neutral position inwhich the nystagmus slows or stops (Gay et al.,1974). The present report describes a patient withKDS syndrome and CN. The occurrence of two rareabnormalities suggests that their association is morethan a mere coincidence.

Case reportAn I 1-year-old male child was seen by us in Sep-

tember, 1980 with complaints of failure to grow,constipation, cold intolerance, loss of initiative andsomnolence of 3-4 years duration. His school per-formance was poor and he took little interest ingames. Developmental milestones up to the age of3 years were normal, although the parents wereaware of the abnormal eye movements he had hadsince early infancy. His younger brother, 4 years old,was normal and there was no history of dwarfism,goitre, or eye movement disorders in other membersof the family.

He had an infantile look, dull facies and dry skin.His height was 101 cm (< 3rd percentile) withupper/lower segment ratio of 1 2. The body weightwas 16-2 kg (<3rd percentile) and the headcircumference was 49 cm. All these parameterscorresponded to the age of 3-4 years (Fig. 1).There was no thyroid swelling. He was slow torespond to questions and the IQ was 78. Muscleswere bulky, especially in the calves. There was mildproximal weakness (power grade 4/5) at the shoul-ders. He had a waddling gait and was unable to getup from the sitting position unaided. Deep tendonjerks were slowed in contraction and relaxation,especially at the ankles. Neuro-ophthalmologicalexamination disclosed normal visual acuity and anormal optic fundus in each eye. Ocular movementswere full. Coarse horizontal nystagmus was evidentin all directions of gaze and he did not have anyoscillopsia. With gaze 10-20° to the left of primaryposition, the nystagmus diminished markedly andhe had a constant head turn to the right side (Fig. 1).The nystagmus was absent on convergence and therewas no vertical nystagmus. No other neurologicaldeficit was demonstrable and the rest of the systemicexamination showed no abnormality.

Laboratory findingsNormal investigations included urine analysis,

haematocrit, blood biochemistry and radiographsof chest and skull. Serum cholesterol was 5-16mmol/l. Electrocardiogram showed a low voltagegraph with heart rate of 70/min. Skeletal X-raysdisclosed normal upper femoral epiphyses and onlythree carpal bones (Fig. 2), which corresponded tothe retarded bone age of 3 years. Thyroid functiontests showed: PBI 228-5 nmol/l (normal 315-630nmol/l), serum thyroxine (T4) 20-6 nmol/l (normal87-5-148 nmol/l), serum triiodothyronine (T3) 0-6nmol/l (normal 0-9-1-2 nmol/l. Muscle enzymes:

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308 Clinical reports

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FIG. 1. Patient before therapy. Dwarfism, disproportionatelyshort limbs in relation to trunk, bulky muscles and the charac-

teristic head posture are apparent.

serum aldolase 15 SL units/ml (normal 2-8 SLunits/ml), serum creatine kinase 11 Sigma units/ml(normal 3-13 Sigma units/ml).Electromyography (EMG) was done with Medelec

MS 6 Electromyograph under standard conditionswith concentric needle electrodes. The calf musclesshowed no spontaneous activity at rest, motor unitpotentials of 50-100 ,uV in amplitude and 2-4 msecin duration with 30% polyphasic potentials, andnormal recruitment pattern on maximal voluntaryactivity. These findings suggested a myopathy.Electronystagmography confirmed the clinical fea-tures of the nystagmus and showed the null point10-12o to the left of primary position (Fig. 3).He was treated with L-thyroxine 50 ,ug/day, gradu-

ally stepped up to 100 ,g/day. He was alert, atten-tive and relieved of the constipation when last seenin July 1981. Pulse rate was 92/min. There wasdecrease in calf muscle size and no girdle muscleweakness was demonstrable. The nystagmus per-sisted.

DiscussionThe KDS syndrome refers to the unusual symp-

tom complex of muscle hypertrophy with childhoodhypothyroidism (Najjar and Nachmann, 1965;Spiro et al., 1970). The muscular involvement isgeneralized, prominent in the calf muscles, givingthese children an athletic appearance (Najar andNachmann, 1965). EMG studies in hypothyroidismhave shown normal to frankly myopathic changes(Waldstein et al., 1958; Schwarz and Rose, 1963).Although there is an intimate relationship betweenthyroid function and muscle metabolism, the struc-tural functional relationship is unclear and thepathogenesis of muscle hypertrophy in hypothyroid-ism is unknown. The changes on pretreatmentbiopsy have been shown to reverse completely withthyroid therapy (Spiro et al., 1970). The clinical

A

FIG. 2. X-ray picture of the wrist. Shows three carpal bones only.

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Clinical reports 309

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FIG. 3. Electronystagmogram. Horizontal nystagmus on (A) centre gaze, (B) rightward gaze, (C)leftward gaze and (D) upgaze. Decrease or absence of nystagmus on (E) convergence and (F) atnull point 10-12o to left of primary position.

features and hormone profile in our patient arediagnostic of sporadic thyroprivic hypothyroidism.The bulky muscles, proximal muscular weaknessand EMG findings indicated hypertrophic myo-pathy. Decrease in muscle size and increase inmuscle power on thyroid replacement therapy un-equivocally establish its relation to hypothyroidism.Anthropometric and radiological findings date theonset of overt thyroid deficiency to around the ageof 3 years.A good account of the clinical characteristics of

CN is given by Gay et al. (1974). Usually pendularin primary position, the nystagmus acquires a jerk-type character on lateral gaze and is markedlyreduced or abolished on convergence. The nystag-

mus beats horizontally in all fields of gaze, and ahorizontally beating nystagmus in upgaze is almostdiagnostic of CN. There is an eccentric neutralposition where the nystagmus slows or stops andmost patients will develop a constant characteristichead posture. The nystagmus appears at birth orsoon after and the patients usually have no visualsymptoms. In the differentiation of congenital fromacquired nystagmus, exploration of the three fea-tures (upgaze, null point and convergence effect) byelectronystagmography may provide decisive in-formation (Barber and Stockwell, 1976). The clinicalfeatures and electronystagmogram in the presentpatient are pathognomonic of CN.The association of CN and hypothyroidism has

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310 Clinical reports

been documented possibly only once in the literature.Schulman and Crawford (1969) described 5 cases ofhypothyroidism with CN. CN is usually hereditary(Gay et al., 1974) but in patients with hypothyroid-ism no family history was obtained (Schulman andCrawford, 1969). Although prompt replacementtherapy has been shown to result in the disappear-ance of the nystagmus in one of the cases reportedby Schulman and Crawford (1969), the majority oftheir patients continued to manifest nystagmusdespite adequate thyroid therapy. The patient underdiscussion exhibited no change in the nystagmusduring the 10-month period of replacement therapy.The basic pathology in CN is unknown; the

classical motor-defect type may involve the corti-copontine pathways, possibly the result of failureor delay in their maturation (Cogan, 1967). There isexperimental evidence to indicate impairment in thedevelopment of the nerve cell processes and retardedmyelination of the axon in the central nervous sys-tem in hypothyroidism (Greene, 1976). Thesechanges are largely irreversible, a fact reflected inthe poor response of the neurological impairment todelayed treatment of the human cretin (Man, Mer-mann and Cooke, 1963). Although the onset of overthormone deficiency in our patient was at about 3years of age, vulnerable areas in the central nervoussystem might have been involved even in the sub-clinical stage. This might explain the isolatedrestricted involvement of the oculomotor system inthe present patient. It is an established fact that defi-ciency of the postnatal concentration of thyroxineor inadequate replacement therapy in congenital

hypothyroidism may promote normal physicalgrowth, but can leave irreparable imprints on thecentral nervous system development (Man et al.,1963).

ReferencesBARBER, H.O. & STOCKWELL, C.W. (1976) Manual ofElectro-

nystagmography, p. 89. C.V. Mosby Company, SaintLouis.

COGAN, D.G. (1967) Congenital nystagmus. CanadianJournal of Ophthalmology, 2, 4.

GAY, A. J., NEWMAN, N.M., KELTNER, J. L. & STROUD, M.H.(1974) Eve Movement Disorders, p. 66. C.V. Mosby Com-pany, Saint Louis.

GREENE, R. (1976) The thyroid gland: its relationship toneurology. In: Handbook of Clinical Neurology, Vol. 27(Ed. by Vinken, P.J. & Bruyn, G.W.), p. 255. North-Hol-land Publishing Company, Amsterdam.

MAN, E.B., MERMANN, A.C. & COOKE, R.E. (1963) Thedevelopment of children with congenital hypothyroidism.A note on early, temporary replacement therapy for 2goitrous infants. Journal of Pediatrics, 63, 926.

NAJJAR, S.S. & NACHMANN, H.S. (1965) The Kocher-Debr&S6m6laigne syndrome. Hypothyroidism with muscu-lar 'hypertrophy'. Journal of Pediatrics, 66, 901.

SCHULMAN, J.D. & CRAWFORD, J.D. (1969) Congenitalnystagmus and hypothyroidism. New England Journal ofMedicine, 280, 708.

SCHWARZ, G.A. & ROSE, E. (1963) Neuromyopathies andthyroid dysfunction. Some unusual associations. ArchivesofInternal Medicine, 112, 555.

SPIRO, A.J., HIRANO, A., BEILIN, R.L. & FINKELSTEIN, J.W.(I 970) Cretinism with muscular hypertrophy (Kocher-Debr6-S6m6laigne syndrome). Histochemical and ultra-structural study of skeletal muscle. Archives of Neurology,23, 340.

WALDSTEIN, S.S., BRONSKY, D., SHRIFTER, H.B. & OESTER,Y.T. (1958) The electromyogram in myxedema. Archivesof Internal Medicine, 101, 97.

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