Case presentation: UNC80 deficiency (MIM 616801) due to biallelic pathogenic variants in UNC80 is characterized with neonatal hypotonia, neurodevelopmental delay and severe intellectual disability associated with seizures, postnatal growth delay, subtle dysmorphic features and sleeping difficulties. Fewer than 50 affected individuals have been described to date.

Two siblings, a brother and sister, presented to the genetics clinic. The male child presented at 9 months with poor growth, hypotonia and neurodevelopmental delay. He was not overtly dysmorphic but had a long face and high arched palate. Both his testicles didn’t descend. Extensive genetic testing which included chromosomal studies, a chromosomal microarray and metabolic investigation including transferrin isoelectric focusing were normal. A MRI of his brain was also normal. His sister was born when he was 4 years old with similar features. Her features was mild but she also had growth delay and hypotonia. Whole exome sequencing of both children identified a likely pathogenic homozygous variant (UNC80:c.5757delC) in the UNC80 gene. Their mother was confirmed to be a carrier for this variant.

UNC80 deficiency is an autosomal recessive disorder resulting in deleterious disturbance in the NALCN channel complex. There is no cure but management includes developmental services and educational support, treatment of sleep difficulties, seizures and irritability, feeding by gastrostomy and orthopaedic management of scoliosis and contractures. Life expectancy is reduced with the oldest individual documented being 17 years old. Genetic counselling and prenatal diagnosis can be offered for families.

Engela Magdalena Honey
University of Pretoria
South Africa

Barend C Vorster
North-West University
South Africa

Marli Dercksen
North-West University
South Africa

Maryke Schoonen
North-West University
South Africa

Engela Helena Conradie
North-West University
South Africa