John Libbey Eurotext

Drop episodes in Coffin-Lowry syndrome: an unusual type of startle response Volume 2, numéro 3, Septembre 2000

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  • Drop episodes in Coffin-Lowry syndrome: an unusual type of startle response

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Coffin-Lowry syndrome (CLS) was described by Coffin et al. [1] and Lowry et al. [2] in 1966 and 1971 respectively and was recognised as a clinical entity by Tentamy et al. [3]. It is transmitted by X-linked semi-dominant inheritance. The gene maps to Xp 22 [4, 5]. This dysmorphic syndrome is recognisable in males, who are usually severely retarded and have the following facial features: hypertelorism with down-slanting palpebral fissures, broad nose with thick septum and large and bow-shaped mouth with prominent everted lips. It is often associated with microcephaly, hypotonia, puffy proximal digits, thick fingers with tapered ends. Pectum carinatum or excavatum has been commented on and severe kyphoscoliosis develops in older patients. Women can also be affected, but the full manifestation is rare in these cases [6]. This article describes a case of Coffin-Lowry syndrome in a male patient who presents drop episodes precipitated by sudden auditory stimuli. These are included in the group of pathologically exaggerated startle responses among which are described: startle epilepsy, hyperekplexia, jumping and uncategorized anormal startle reponses [7]. In this article we discuss the relationship between this unusual type of startle response and Coffin-Lowry syndrome.

Case report

Clinical findings

The patient, an 18-year-old boy, was the result of a normal pregnancy and delivery, of unrelated healthy parents. He had a brother affected by the syndrome who recently died of kidney failure. At the age of 10 months he suffered febrile seizure status during the course of an acute bronchopneumonia. Since then, he has been treated with phenobarbital without recurrence of seizures. When he was 11 years old he began falling down for no obvious reason. Attacks were induced by unexpected auditory stimuli. He was treated with antiepileptic drugs (valproic acid, phenobarbital, carbamazepine) which proved to be ineffective. He was admitted to our hospital at the age of 12, having been referred from another center, where he was diagnosed with refractory epilepsy. He was developmentally retarded with characteristic features of Coffin-Lowry syndrome (figures 1, 2 and 3). His karyotype was 46 XY. Fundoscopic examination disclosed bilateral optic atrophy. Interictal EEG recordings were normal, both awake and asleep. Both cranial computed tomography and magnetic resonance imaging showed slight ventriculomegaly. Somatosensory, visual and brain stem potentials were not remarkable. He was tried on clonazepam in association with lamotrigine without any effective reponse. Video-EEG recording was performed in order to better understand these episodes.

Drop episodes were recorded by video-EEG. We also study the surface EMG simultaneously and the electrodes were placed on spinal, deltoides and quadriceps muscles. The EEG was recorded with conventional electrodes fixed with colodion, following the international 10-20 system, recording both ictal and interictal registers.

Results

Video-EEG recording showed a drop episode immediately after the stimuli. He fell down with preservation of consciousness. Muscle tone, seemed to be lost in both legs. After a few seconds he stood up. The EEG during the episode was unremarkable except for the baseline shift resulting from motion. EMG activity showed a silent state in the quadriceps muscle, but was normal in the upper extremities as well as in the spinal muscles. There was no evidence of myoclonic activity either before or after the silent state.

Discussion

Our results showed that these drop episodes were due to a sudden loss of muscle tone in the legs caused by unexpected auditory stimuli. Concomitant EEG did not show paroxysmal discharges, indicating that. The falls were not epileptic in origin. In the literature, there have been reports of CLS associated with cataplexy, but with no electrophysiological correlation. An exception is Nakamura´s report of a female patient with CLS and drop episodes precipitated by sudden, unexpected auditory or tactile stimuli. These results showed some similarities to ours as regards the electrophysiological and clinical findings. Both patients were teenagers at the onset of these drop episodes. The author postulates that the abnormally enhanced muscle suppression and loss of muscle excitation observed in his patient may have been caused by abnormal facilitation of suppression response over muscle activation through PGO-like waves, although no electrophysiological evidence was available. Clonazepam effectively stopped the drop episodes. The differential diagnoses include [8]: other startle responses due to epileptic and nonepileptic paroxysmal disorders. Startle epilepsy [9] is characterised by tonic or myoclonic seizures associated with paroxysmal discharges revealed by EEG. Hyperekplexia is an autosomal-dominant genetic disorder that exhibits stimuli-induced generalised myoclonic jerks and it has been recently linked to the short arm of chromosome 5, although many sporadic cases have been reported [10]. Jumping responses associated with speaking and other behaviour after sudden stimuli is another diagnostic possibility. Finally, we must mention cataplexy, an ancillary symptom of narcolepsy, that involves the sudden loss of muscle tone without altered consciousness, usually brought on by sudden excitement or emotional influence. As regards to treatment, clonazepam effectively stopped the drop episodes of Nakamura´s patient. Although we think that neither are epileptic disorders, it is know that this drug is very effective in startle epilepsy and in hyperekplexia. Probably this would suggest a common pathway in both disorders as a case of CLS with cataplexy was recently presented [11]. The patient had sudden drop episodes concomitant with normal EEG. It was for this reason that we started treatment with clorimipramine, which has proved to be effective in narcolepsy/cataplexy syndrome. After one year of treatment, daily drops episodes were reduced to a frequency of one or twice a month.

CONCLUSION

Our electrophysiological results showed that these drop episodes are not epileptic in origin, and that they are due to loss of muscle tone in the lower limbs, as was highlighted on EMG. We recognize them as an unusual type of startle response associated with CLS.

Clorimipramine has proved to be effective in reducing the frequency of drop episodes, although we admit that a longer follow-up is necessary and a greater number of patients studied, to give definitive conclusions.