title: Early Infantile Epileptic Encephalopathy in an STXBP1 Patient with Lactic Acidemia and Normal Mitochondrial Respiratory Chain Function.
abstract: A wide range of clinical findings have been associated with mutations in Syntaxin Binding Protein 1 (STXBP1), including multiple forms of epilepsy, nonsyndromic intellectual disability, and movement disorders. STXBP1 mutations have recently been associated with mitochondrial pathology, although it remains unclear if this phenotype is a part of the core feature for this gene disorder. We report a 7-year-old boy who presented for diagnostic evaluation of intractable epilepsy, episodic ataxia, resting tremor, and speech regression following a period of apparently normal early development. Mild lactic acidemia was detected on one occasion at the time of an intercurrent illness. Due to the concern for mitochondrial disease, ophthalmologic evaluation was performed that revealed bilateral midperiphery pigmentary mottling. Optical coherence tomography (OCT) testing demonstrated a bilaterally thickened ganglion cell layer in the perifovea. Skeletal muscle biopsy analysis showed no mitochondrial abnormalities or respiratory chain dysfunction. Exome sequencing identified a de novo c.1651C>T (p.R551C) mutation in STXBP1. Although mitochondrial dysfunction has been reported in some individuals, our proband had only mild lactic acidemia and no skeletal muscle tissue evidence of mitochondrial disease pathology. Thus, mitochondrial dysfunction is not an obligate feature of STXBP1 disease.
authors.affiliation: Center for Applied Genomics, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
authors.forename: Dong
authors.initials: D
authors.lastname: Li
authors.affiliation: Center for Applied Genomics, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA; Division of Human Genetics, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Bhoj
authors.affiliation: Division of Human Genetics, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA; Division of Metabolic Disease, Department of Pediatrics, The Children's Hospital of Philadelphia and the Perelman School of Medicine, Philadelphia, PA 19104, USA.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: McCormick
authors.affiliation: Center for Applied Genomics, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
authors.forename: Fengxiang
authors.initials: F
authors.lastname: Wang
authors.affiliation: Center for Applied Genomics, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
authors.forename: James
authors.initials: J
authors.lastname: Snyder
authors.affiliation: Center for Applied Genomics, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
authors.forename: Tiancheng
authors.initials: T
authors.lastname: Wang
authors.affiliation: Center for Applied Genomics, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Center for Applied Genomics, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Kim
authors.affiliation: Center for Applied Genomics, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
authors.forename: Rosetta
authors.initials: R
authors.lastname: Chiavacci
authors.affiliation: Center for Applied Genomics, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
authors.forename: Lifeng
authors.initials: L
authors.lastname: Tian
authors.affiliation: Division of Human Genetics, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA; Division of Metabolic Disease, Department of Pediatrics, The Children's Hospital of Philadelphia and the Perelman School of Medicine, Philadelphia, PA 19104, USA.
authors.forename: Marni J
authors.initials: MJ
authors.lastname: Falk
authors.affiliation: Center for Applied Genomics, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA; Division of Human Genetics, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
authors.forename: Hakon
authors.initials: H
authors.lastname: Hakonarson