A Novel NALCN Homozygote Variant in Non-related Infants with IHPRF1 Syndrome: A Report of 2 Cases

Abstract

Introduction: Sodium leak channel, non-selective (NALCN) is an ion channel with an important function in neuronal excitability. The activity of NALCN is essential in the balance of rhythmic behaviors. Infantile hypotonia with psychomotor retardation and characteristic facies 1 (IHPRF1), which occurs due to biallelic NALCN variants, leads to dysmorphic characteristics and global developmental delay. We hereby report 2 non-related patients with IHPRF1 syndrome. Case Presentation: The first case was a 1 - year-old girl referred to our center because of constipation and poor weight gain, and the other was a 2 - year-old girl presenting with hypotonia, constipation, and poor weight gain. Whole exome sequencing led to the detection of homozygote NALCN variants. Interestingly, in both cases, a novel variant of c.1434 + 1G>A in NACLN was identified, which, to the best of our knowledge, has not been reported as a pathogenic variant so far. Conclusions: NALCN dysfunctions lead to rare yet clinically significant disorders. Due to the potential mortality, further studies are essential for a more comprehensive understanding of these rare disorders.