An Unusual Presentation of Leber Hereditary Optic Neuropathy-Plus Case Caused by a Novel DNAJC30 Variant

• Published in: American journal of medical genetics. Part A p. e63902
• Main Authors: Şenol, Hüseyin Bahadır, Soydemir, Didem, Polat, Ayşe İpek, Aydın, Adem, Hız, Ayşe Semra, Yiş, Uluç
• Format: Journal Article
• Language: English
• Published: United States 15-10-2024
• Subjects: Leber hereditary optic neuropathy; exome sequencing; idiopathic intracranial hypertension; neuromyelitis optica spectrum disorder; ventriculoperitoneal shunt
• ISSN: 1552-4825; 1552-4833; 1552-4833
• DOI: 10.1002/ajmg.a.63902

Leber hereditary optic neuropathy (LHON) is characterized by vision loss due to the degeneration of retinal ganglion cells. LHON-Plus refers to LHON with additional extraocular findings. Neurological conditions observed in LHON-Plus include seizures, encephalopathy, movement disorders, neuropathy, and myopathy. Herein, we present a case with atypical LHON-Plus caused by a novel DNAJC30 disease-causing gene variant. A 15-year-old boy presented with acute headache, and blurred and decreased vision in both eyes. Although initial evaluation pointed toward idiopathic intracranial hypertension, the subsequent diagnostic process revealed unusual features like area postrema syndrome and T2 hyperintensity in brain magnetic resonance imaging. Consequently, antibody-negative neuromyelitis optica spectrum disorder (NMOSD) was diagnosed and treatment was commenced. Recurrent episodes of elevated intracranial pressure necessitated the insertion of a ventriculoperitoneal shunt. Exome sequencing (ES) revealed a novel homozygous variant in the DNAJC30 gene 2 years after symptom onset. Atypical LHON presentations due to nuclear gene mutations may mimic other neuroinflammatory conditions like NMOSD, necessitating thorough clinical evaluation and genetic testing. ES plays a crucial role in diagnosing complex neurological cases, enabling the identification of novel genetic variants associated with LHON and related disorders.