Childhood Frontal Lobe Epilepsies: Etiology, Classification, and EEG Findings
Nicolas Abreu, Laura Biederman, Zarsha Khuhro, Kandamurugu Manickam, Emily de los Reyes
Objective: To elucidate the role of skin biopsy in establishing a diagnosis of CLN6 Batten disease, an autosomal recessive neurodegenerative lysosomal storage disorder, in the setting of uncertain genetic findings.
Methods: A retrospective review was performed of a 5 year 9 month old female presenting with symptoms suggestive of late-infantile Batten disease.
Results: The proband presented for neurological evaluation after behavioral dysregulation noted at 1 year 10 months, ataxia at around 2 years of age, and generalized myoclonic epilepsy at 4 years of age. She had speech delay and intermittent dysfluency. Examination was notable for hypotonia, myoclonus and lower extremity clonus. Brain magnetic resonance imaging at 5 years 5 months revealed non-specific reduced cerebral and cerebellar volumes and patchy bilateral T2 hyperintensities of periventricular and deep white matter. Fundoscopic exam revealed bilateral mild macular pigment changes. A next-generation sequencing epilepsy panel and subsequent parental testing revealed biallelic variants in CLN6 – a maternally inherited known pathogenic exon 1 deletion and a paternally inherited missense variant of uncertain significance, c.679G>A, p.(Glu227Lys). Exome sequencing did not reveal any additional clinically relevant findings. Skin biopsy was then performed and electron microscopy demonstrated cytoplasmic granular osmiophilic densities and lipofuscin, suggestive of Batten disease.
Conclusions: Skin biopsy remains a relevant tool in the evaluation of Batten disease, and should be considered to help adjudicate variants of uncertain significance especially when treatment would be possible.
Keywords: CLN6 disease; Batten disease; Neuronal ceroid lipofuscinosis; Neurogenetics; Skin biopsy
Nicolas Abreu
NYU Langone Health
Laura Biederman
The Ohio State University Wexner Medical Center
Zarsha Khuhro
Nationwide Children's Hospital
Kandamurugu Manickam
Nationwide Children's Hospital
Emily de los Reyes
Nationwide Children's Hospital
Objective: To elucidate the role of skin biopsy in establishing a diagnosis of CLN6 Batten disease, an autosomal recessive neurodegenerative lysosomal storage disorder, in the setting of uncertain genetic findings.
Methods: A retrospective review was performed of a 5 year 9 month old female presenting with symptoms suggestive of late-infantile Batten disease.
Results: The proband presented for neurological evaluation after behavioral dysregulation noted at 1 year 10 months, ataxia at around 2 years of age, and generalized myoclonic epilepsy at 4 years of age. She had speech delay and intermittent dysfluency. Examination was notable for hypotonia, myoclonus and lower extremity clonus. Brain magnetic resonance imaging at 5 years 5 months revealed non-specific reduced cerebral and cerebellar volumes and patchy bilateral T2 hyperintensities of periventricular and deep white matter. Fundoscopic exam revealed bilateral mild macular pigment changes. A next-generation sequencing epilepsy panel and subsequent parental testing revealed biallelic variants in CLN6 – a maternally inherited known pathogenic exon 1 deletion and a paternally inherited missense variant of uncertain significance, c.679G>A, p.(Glu227Lys). Exome sequencing did not reveal any additional clinically relevant findings. Skin biopsy was then performed and electron microscopy demonstrated cytoplasmic granular osmiophilic densities and lipofuscin, suggestive of Batten disease.
Conclusions: Skin biopsy remains a relevant tool in the evaluation of Batten disease, and should be considered to help adjudicate variants of uncertain significance especially when treatment would be possible.
Keywords: CLN6 disease; Batten disease; Neuronal ceroid lipofuscinosis; Neurogenetics; Skin biopsy
Nicolas Abreu
NYU Langone Health
Laura Biederman
The Ohio State University Wexner Medical Center
Zarsha Khuhro
Nationwide Children's Hospital
Kandamurugu Manickam
Nationwide Children's Hospital
Emily de los Reyes
Nationwide Children's Hospital
Nicolas Abreu
NYU Langone Health
NYU Langone Health