Pathogenic variant in NFIA associated with subdural hematomas mimicking nonaccidental trauma.

Subdural hematoma (SDH) in infants raises the concern for nonaccidental trauma (NAT), especially when presenting with associated injuries. However, isolated SDH could be caused by multiple etiologies. NFIA (MIM# 600727) encodes nuclear factor I A protein (NFI-A), a transcription factor which plays important roles in gliogenesis. Loss-of-function variants in NFIA are associated with autosomal dominant brain malformations with or without urinary tract defects (MIM# 613735). Intracranial hemorrhage of various types besides SDH has been reported in patients with this condition. Here, we report a patient with a heterozygous novel NFIA pathogenic variant affecting splicing who initially presented with SDH concerning for NAT. We also review previous NFIA-related disorder cases with intracranial hemorrhage. This report emphasizes the importance of genetic evaluation in infants presenting with isolated SDH.

White Matter Lesions Detected by Magnetic Resonance Imaging in Neonates and Children With Congenital Myotonic Dystrophy.

BACKGROUND: Congenital myotonic dystrophy (CDM1) is an autosomal dominant genetic disorder caused by abnormal cytosine-thymine-guanine trinucleotide repeat expansion that results in weakness and cognitive deficits. Studies detailing brain magnetic resonance imaging (MRI) findings in neonates and children with this condition are limited. OBJECTIVE: We evaluated the brain MRI findings in children, including neonates with CDM1, to assess the nature of central nervous system involvement and progression of MRI lesions over time. METHODS: The Cincinnati Children's Hospital neuromuscular disease database was used to identify 16 patients with CDM1 with genetically proven CDM1 who had undergone brain MRI. Hospital charts were reviewed to collect clinical information. RESULTS: Ninety-four percent of patients had an abnormal MRI showing injury to the white matter. Nine patients underwent imaging before eight days of life, and eight of these patients showed signs of injury to the white matter. Three neonates had follow-up MRI scans, and all showed progression of injury. Seven patients had the first MRI between age 29 days and 22 years, and all had abnormalities involving the white matter. Two patients had additional congenital brain malformations, and one patient also harbored a mutation in CDKL5 with resultant epilepsy. CONCLUSIONS: White matter abnormalities are found in patients with CDM1, even in the neonatal period. Many patients present with hypoxia and receive a diagnosis of hypoxic-ischemic encephalopathy and may even undergo therapeutic hypothermia. If MRI findings of white matter injury do not correlate with hypotonia and weakness, further evaluation for CDM1 should be considered.