A case of severe autosomal dominant spinal muscular atrophy with lower extremity predominance caused by a de novo BICD2 mutation.

Abstract Background Heterozygous variants in BICD2 cause autosomal dominant spinal muscular atrophy with lower extremity predominance. These variants are also identified in individuals with severe forms of congenital muscle atrophy representing arthrogryposis multiplex. Case report A girl was born with severe muscle weakness and respiratory distress. A fetal ultrasound had detected polyhydramnios and multiple joint contractures in utero. She was born with severe muscle weakness and respiratory distress. Bilateral hip joint dislocation and multiple bone fractures were also present at birth. Although she depends on medical care, including assisted ventilation and tube feeding, she has reached eight years of age. Her motor developmental skills were reduced owing to muscle weakness and deformity of her lower extremities, whereas her cognitive development slowly but steadily grew. Whole exome sequencing revealed a novel de novo missense BICD2 variant (c.1625G > A, p.(Cys542Tyr)), which was evaluated as likely pathogenic. Conclusion This is the first case report of a severe form of spinal muscular atrophy with lower extremity predominance caused by a de novo BICD2 variant in Japan.