Whole exome sequencing revealed mutations in FBXL4, UNC80, and ADK in Thai patients with severe intellectual disabilities.

Intellectual disabilities (ID) are etiologically heterogeneous. Advanced molecular techniques could be helpful in identification of the underlying genetic defects. We aimed to characterize clinical and molecular features of three Thai patients with ID. Patient 1 had ID, hypotonia and lactic acidosis. Patient 2 had ID and growth failure. Patient 3 had ID, seizure, diarrhea and hypoglycemia. Whole exome sequencing found that Patient 1 was homozygous for a nonsense, c.1303C>T (p.Arg435Ter), mutation in FBXL4, a gene responsible for encephalomyopathic mitochondrial DNA depletion syndrome-13 (MTDPS13). Patient 2 was compound heterozygous for two novel mutations, c.3226C>T (p.Arg1076Ter) and c.3205C>T (p.Arg1069Ter), in UNC80, a known gene of infantile hypotonia with psychomotor retardation and characteristic facies-2 (IHPRF2). Patient 3 was homozygous for a novel missense, c.427T>C (p.Cys143Arg), mutation in ADK, a known gene of adenosine kinase deficiency leading to hypermethioninemia. This study expands the mutational spectra of ID genes.

Rare epileptic syndrome of ring chromosome 20 with epileptic encephalopathy: a case report.

The authors report the clinical features, electroencephalography (EEG), neuroimaging (brain magnetic resonance image-MRI), and cytogenetic findings of a young female patient with rare cytogenetic anomalies characterized by de novo 46, XX, r (20) (p13q13.3). The patient had a history of mild mental retardation, emotional liability and intractable epilepsy with non-convulsive status epilepticus. The MRI brain showed focal cerebral dysplasia over the left temporal region. The multiple seizures were refractory to antiepileptic medications and prolonged, confused state with or without a motor component. The continuous video-EEG monitor showed epileptiform discharges over bilateral frontal regions with frontal origin. The symptoms were relieved after midazolam infusion. A patient who was present with intractable epilepsy with continuous frontal epileptiform discharges, mental retardation, abnormal behavior, without dysmorphic features should be suspected of chromosomal abnormalities especially ring chromosome 20.

Childhood myasthenia gravis: clinical features and outcomes.

OBJECTIVE: To study the clinical features, treatment, outcome and factors that affected the outcome of myasthenia gravis (MG) in children. MATERIAL AND METHOD: Children aged 16 years or less with diagnosed myasthenia gravis (MG) seen at Queen Sirikit National Institute of Child Health over a 15-year period with a minimum follow-up of 6 months were reviewed. Demographic, clinical characteristics, treatment and the outcome were analyzed. RESULTS: One hundred and nineteen MG patients, 100 patients (84%) were ocular MG (OMG) and 19 patients (16%) were generalized MG (GMG). Median age of onset was 4.1 years. OMG patients had the age of onset earlier than GMG patients (p = 0.01). Female to male ratio was 1.8: 1. Ptosis was a clinical feature in 99%, accompanied with ophthalmoplegia in 63%, diplopia in 19.3%, extremity weakness in 13.4%, respiratory muscle weakness in 9%, head tilt in 10.1%, dysphagia in 7.5%, hyperthyroidism in 3.4% and epilepsy in 2.5%. One hundred and six patients who had ptosis as the initial symptom 67% were bilateral ptosis, 33% were unilateral ptosis, 10 patients progressed to GMG in 2 years. Almost all patients were treated with pyridostigmine and prednisolone. At the end of follow-up, 60.5% had pharmacological remission for more than 3 months, 18.5% had complete remission without medication. No definite factors associated with the remission were identified. CONCLUSION: OMG is the majority of MG patients and the age of onset is earlier than GMG. Early treatment by prednisolone may have the favorable effect on OMG in the progression to GMG and subsequent involvement to the other eye.