Influence of a mutation of the calcium ATPase 2 (SERCA 2) gene in patients with Darier's disease on the central and peripheral nervous system

Objective: To investigate neurological manifestations in patients with Darier's disease Introduction: Darier's disease is an autosomal dominant skin disorder characterized by warty papules and plaques in the seborrheic area (central trunk, flexures, scalp, and forehead), palmoplantar pits, and nail abnormalities. ATP2A2, which encodes the sarcoplasmic reticulum calcium ATPase 2 (SERCA2) pump, has been identified as the defective gene in Darier's disease. SERCA2 belongs to a family of P-type membrane bound ATPase, which pumps calcium from the cytoplasm into reservoirs in the endoplasmic reticulum. Up to now neurological manifestations of the disease have not been described. Methods: 6 patients with Darier's disease were seen by a neurologist. AEP, nystagmography, EMG of the quadriceps muscle, and electroneurography of the lower limb were performed. Additionally isometric contractions of the adductor pollicis muscle were recorded after supramaximal ulnar nerve stimulation. The compound muscle action potential (CMAP) was recorded by surface electrodes. Results: In 5/6 patients the electrophysiological investigations including the electromyography were normal. One patient who was affected most heavily by Darier's disease showed a generalized muscular atrophy and myopathy in the EMG. The muscle contraction test was pathological in all patients. The contraction time and the half relaxation time (1/2 RT) were prolonged. In 5/6 patients the twitch potentiation after 2Hz stimulation was not detectable. Discussion: We could show for the first time that patients' with Darier's disease had a pathological muscle contraction. No pathological changes of the central nervous system were detectable. These muscle alterations correspond very well with the known mutation in the SERCA2 gene, coding for a calcium ATPase 2, and suggest a relevant physiological influence of the mutation for the muscle physiology.