The disease spectrum associated with SLC18A3 mutations ranges from congenital myasthenic syndromes (CMS) to fetal akinesia deformation sequence (FADS). CMS is characterized by muscle fatigability and weakness, (episodes of) respiratory insufficiency, feeding difficulties, and arthrogryposis. Complete loss of SLC18A3 function appears to lead to FADS – a severe prenatal phenotype characterized by fetal akinesia, arthrogryposis, hydrops, and fetal anomalies.
There are only rare reports of SLC18A3-associated disease in the literature: CMS has been reported in six families and FADS in one Finnish family. The calculated incidence of SLC18A3-associated FADS in the Finnish population is 1:160,000 – based on the carrier frequency of the variant in the Finnish population (approximately 1/200 in gnomAD).
SLC18A3-associated diseases are inherited in an autosomal recessive manner.
SLC18A3