Case Report: Neonatal-onset parkinsonian-pyramidal syndrome caused by novel compound heterozygous FBXO7 variants

Abstract

Background Early-onset parkinsonism is often associated with genetic factors. Pathogenic variants in the FBXO7 gene are a rare cause of early-onset parkinsonism, typically presenting as parkinsonian-pyramidal syndrome (PPS), also known as Parkinson's disease-15 (PARK15). To date, only three cases of infantile-onset PARK15 have been reported worldwide. Herein, we describe a Chinese patient with neonatal-onset PARK15, who carried novel compound heterozygous FBXO7 variants. Case presentation A 37-hour-old male infant with generalized limb rigidity was referred for evaluation of neonatal-onset hypertonia. Physical examination revealed abnormal vocalization, poor sucking and swallowing (requiring nasogastric tube feeding), and abdominal muscle rigidity. Pyramidal involvement was evidenced by positive Babinski sign and its equivalents, together with hyperreflexia, while extrapyramidal findings included lead-pipe rigidity of all four limbs with markedly increased muscle tone. Whole-exome sequencing identified two compound heterozygous nonsense variants in FBXO7, c.376G > T (p.Gly126*) and c.1033C > T (p.Arg345*), inherited from the father and mother, respectively. Both variants were classified as pathogenic. Following diagnosis, the parents elected to discontinue active in-hospital treatment, and the infant was discharged home. Nevertheless, a trial of oral levodopa was initiated at home. Despite levodopa treatment, the infant showed no clinical improvement and died at 89 days of age. Conclusions To our knowledge, this is the first reported case of neonatal-onset PARK15 caused by FBXO7 variants. This case expands the mutational and clinical spectrum of PARK15 in the neonatal period.