Effect of adrenocorticotropic hormone therapy for epileptic spasms developing after the age of 1 year

AbstractPurposeEpileptic spasms sometimes begin after the first year of life, and such seizures are recognized as late-onset spasms (LOS). The prognosis of LOS is poor, and a treatment strategy has not been established. This study aimed to assess the short- and long-term effects of adrenocorticotropic hormone (ACTH) therapy for LOS.MethodsWe investigated the rate of LOS in 22 patients (14 boys and 8 girls) treated with ACTH therapy. The age at onset of LOS and at the start of ACTH therapy ranged from 12 to 94 months (median, 31.6±22.1 months) and from 12.5 to 116 months (median, 37.5±23.7 months), respectively. We investigated the response rate of LOS treated with ACTH therapy, and compared the clinical features between responders (short-term) and nonresponders.ResultsNine (41%) of the 22 patients showed cessation of epileptic spasms within 3 months. The epileptic spasms ceased in four of these nine patients for more than 1 year. The age at onset of LOS was significantly associated with short-term seizure cessation (p<0.05). Patients who achieved short-term cessation of seizures received ACTH therapy within 6 months from the onset of LOS.ConclusionACTH therapy is a potentially effective treatment when started within 6 months from the onset of LOS. A younger age at onset of LOS is associated with a favorable outcome

A Case of Fundus Oculi Albinoticus Diagnosed as Angelman Syndrome by Genetic Testing

Purpose: To report a case of fundus oculi albinoticus diagnosed as Angelman syndrome (AS) via genetic testing. Case Report: This study reports on a 4-year-old boy. Since he had been having respiratory disturbance since birth, he underwent a complete physical examination to investigate the cause. The results indicated that he had various brain congenital abnormalities, such as a thin corpus callosum, as well as hydronephrosis, an atrial septal defect, and skin similar to patients with fundus oculi albinoticus. Examination revealed bilateral fundus oculi albinoticus, mild iridic hypopigmentation, optic atrophy, and poor visual tracking. Genetic testing revealed a deletion in the Prader-Willi syndrome/AS region on chromosome 15, and together with the results of methylation analysis, his condition was diagnosed as AS. Follow-up examinations revealed no change in the fundus oculi albinoticus and optic atrophy, nor did they indicate poor visual tracking. Conclusions: When fundus oculi albinoticus and optic atrophy are observed in patients with multiple malformations, AS should be considered as a differential diagnosis

A Case of Hydranencephaly in Which Ophthalmic Examinations Were Performed

Purpose: We performed ophthalmic examinations, including optical coherence tomography (OCT), on a case diagnosed with hydranencephaly. Case Report: This case involved a female infant born at the gestational age of 35 weeks and 4 days, with the birth weight of 2,152 g, who was one of monochorionic diamniotic twins, and the identical twin died in utero at the gestational age of 24 weeks. After that, examination by fetal echo indicated that she had microcephaly and ventriculomegaly. Postnatal magnetic resonance imaging (MRI) of her head indicated microcephaly and significant enlargement of the lateral ventricle on both sides, with no obvious signs of elevated intracranial pressure. The brain parenchyma of both sides of the frontal lobe, parietal lobe, and occipital lobe had marked thinning, yet that of the temporal lobe, basal ganglia, thalamus, brain stem, and cerebellum had been maintained. Moreover, no obvious hematoma or neoplastic lesions were observed. Ophthalmic examinations indicated that both of her eyes had slight light reflex, attributed to optic nerve atrophy. Examination by use of a hand-held OCT system indicated a layered structure of the retina and thinning of the ganglion cell layer. Flicker electroretinogram (ERG) examination by use of a hand-held ERG system indicated an almost normal wave. However, no clear visual reaction was observed when she was 10 months old. Conclusion: Our findings in this case of hydranencephaly revealed that even though the outer layer functions of the patient’s retina were maintained, extensive damage to her cerebral cortex resulted in poor visual function

Maternal Uniparental Isodisomy of Chromosome 4 and 8 in Patients with Retinal Dystrophy: SRD5A3-Congenital Disorders of Glycosylation and RP1-Related Retinitis Pigmentosa

Purpose: Uniparental disomy (UPD) is a rare chromosomal abnormality. We performed whole-exosome sequencing (WES) in cases of early-onset retinal dystrophy and identified two cases likely caused by UPD. Herein, we report these two cases and attempt to clarify the clinical picture of retinal dystrophies caused by UPD. Methods: WES analysis was performed for two patients and their parents, who were not consanguineous. Functional analysis was performed in cases suspected of congenital disorders of glycosylation (CDG). We obtained clinical case data and reviewed the literature. Results: In case 1, a novel c.57G&gt;C, p.(Trp19Cys) variant in SRD5A3 was detected homozygously. Genetic analysis suggested a maternal UPD on chromosome 4, and functional analysis confirmed CDG. Clinical findings showed early-onset retinal dystrophy, intellectual disability, and epilepsy. In case 2, an Alu insertion (c.4052_4053ins328, p.[Tyr1352Alafs]) in RP1 was detected homozygously. Maternal UPD on chromosome 8 was suspected. The clinical picture was consistent with RP1-related retinitis pigmentosa. Although the clinical features of retinal dystrophy by UPD may vary, most cases present with childhood onset. Conclusions: There have been limited reports of retinal dystrophy caused by UPD, suggesting that it is rare. Genetic counseling may be encouraged in pediatric cases of retinal dystrophy