Epilepsy of Infancy With Migrating Focal Seizures (EIMFS): Expansion of Clinical Phenotypic And Genotypic Spectra

EIMFS is a rare early infantile epileptic encephalopathy with unknown etiology and poor prognosis. This study included 36 patients who were diagnosed with EIMFS. 17/36 cases had causative variants across 11 genes, including 6 novel EIMFS genes: PCDH19, ALDH7A1, DOCK6, PRRT2, ALG1 and ATP7A. 13/36 patients had ineffective seizure control, 14/36 patients had severe retardation and 6/36 patients died. Of them, the genes for ineffective seizure control, severe retardation or death include KCNT1, SCN2A, SCN1A, ALG1, ATP7A and WWOX. 17 patients had abnormal MRI, of which 8 had ineffective seizure control, 7 had severe retardation and 4 died. 13 patients had hypsarrhythmia, of which 6 had ineffective seizure control, 6 had severe retardation and 2 died. Also, 7 patients had burst suppression, of which 1 had ineffective seizure control, 3 had severe retardation and 3 died. This study is the first to report that ALDH7A1, ATP7A, DOCK6, PRRT2, ALG1, and PCDH19 mutations cause the phenotypic spectrum of EIMFS to expand the genotypic spectrum. The genes KCNT1, SCN2A, SCN1A, ALG1, ATP7A and WWOX may be associated with poor prognosis. The patients presenting with MRI abnormalities, hypsarrhythmia and burst suppression in EEG may be associated with poor prognosis.

Malignant Migrating Partial Seizures of Infancy (MMPSI): Expansion of Clinical Phenotypic and Genotypic Spectra

BackgroundMMPSI is a rare early infantile epileptic encephalopathy with unknown etiology and poor prognosis. With the development of genetic techniques, an increasing number of novel pathogenic genes have been shown to be related to MMSPI. This study included 36 patients who were diagnosed with MMPSI; the clinical features, etiology, treatment strategies and outcomes of these patients were determined to explore new genetic etiology and new precision medicine treatment strategies.Results36 patients were enrolled. The main seizure types were focal, tonic and spasms. The main EEG findings were seizure migration and hypsarrhythmia. 17/36 cases had causative variants across 11 genes, including 6 novel MMPSI genes: PCDH19, ALDH7A1, DOCK6, PRRT2, ALG1 and ATP7A. 13/36 patients had ineffective seizure control, 14/36 patients had severe retardation and 6/36 patients died. Of them, the genes for ineffective seizure control, severe retardation or death include KCNT1, SCN2A, SCN1A, ALG1, ATP7A and WWOX. Genes associated with seizure-free, mild-moderate retardation or normal development included PRRT2, SCN2A, ALDH7A1 and PNPO. Vitamin B6 allowed patients with ALDH7A1 and PNPO mutations to achieve seizure-free status, oxcarbazepine was effective for patients with SCN2A, ATP7A, WWOX, and PRRT2 mutations, and ACTH was partly effective for DOCK6 mutation patients with spasms and hypsarrhythmia. 17 patients had abnormal MRI, of which 8 had ineffective seizure control, 7 had severe retardation and 4 (4/17, 23.5%) died. 13 patients had hypsarrhythmia, of which 6 had ineffective seizure control, 6 had severe retardation and 2 died. Also, 7 patients had burst suppression, of which 1 had ineffective seizure control, 3 had severe retardation and 3 died.ConclusionThis study is the first to report that ALDH7A1, ATP7A, DOCK6, PRRT2, ALG1, and PCDH19 mutations cause the phenotypic spectrum of MMPSI to expand the genotypic spectrum. The genes KCNT1, SCN2A, SCN1A, ALG1, ATP7A and WWOX may be associated with poor prognosis. The patients presenting with MRI abnormalities, hypsarrhythmia and burst suppression in EEG may be associated with poor prognosis. Through early diagnosis with genetic tests and the administration of the corresponding precise treatment, the outcomes of MMPSI can be notably improved.

Progressive Deformity of the Lower Limbs in a Patient with KID (Keratitis-Ichthyosis-Deafness) Syndrome

Purpose. Progressive deformity of the lower limbs can be encountered in a long list of syndromic associations. The baseline tool in the management of such disorders is to approach to a definite diagnosis. Methods. We describe a 4-year-old girl who presented with the clinical phenotype and genotype of congenital erythrokeratoderma, keratosis, and sensorineural hearing loss (keratitis-ichthyosis-deafness syndrome) (KID syndrome). She manifested progressive contractures of the knees associated with talipes equinovarus of the feet. The latter deformities were the main reasons behind her severe retardation in acquiring the normal locomotor functions. Results. The analysis revealed mutations in intron 1 of the GJB2 gene of C.32G>A (p.Gly11Glu) and c.35delG in the compound heterozygous state. The presence in the genotype of the “dominant” mutation c.32G>A (p.Glu11Glu) was compatible with the clinical phenotype of KID syndrome. Conclusion. Surgical interventions through the extension of the hamstring tendons have been performed successfully via the application of an external distraction apparatus, namely, Volkov- Oganesyan. The latter procedures resulted in total release of her awkward knee contractures. Eventually, the child was able to regain the physiological alignment of her lower limbs and resume walking. To the best of our knowledge, the overall management of this child could be the first in the literature.

Modern Breeding Approaches for durable Resistance against the parasitic Plant Striga

Crop losses caused by parasitic plants of the genus Striga pose a great danger to the livelihoods of millions of smallholder farmers in Africa. The parasite attaches to host crops and siphons nutrients leading to severe retardation and crop death. Controlling Striga is difficult because of the parasite’s ability to produce large amounts of seeds that can remain dormant in the soil for decades – only germinating in response to chemical cues (strigolactones) from the host. In recent years, breeding crops for host-based resistance has been prioritized. However, such programs have not taken into account Striga’s ability to overcome host resistance. As a result, introduced resistance fails because of increased Striga virulence (infection severity). This article reviews technologies for a new paradigm in Striga resistance breeding that incorporates host resistance breeding with well-informed knowledge of parasite resistance in order to ensure durability of resistance. KEY WORDS: STRIGA, HOST BASED RESISTANCE, GENOME WIDE ASSOCIATION MAPPING, RNA SEQUENCING

Modern Breeding Approaches for Durable Resistance Against the Parasitic Plant Striga

Crop losses caused by parasitic plants of the genus Striga pose a great danger to the livelihoods of millions of smallholder farmers in Africa. The parasite attaches to host crops and siphons nutrients leading to severe retardation and crop death. Controlling Striga is difficult because of the parasite’s ability to produce large amounts of seeds that can remain dormant in the soil for decades – only germinating in response to chemical cues (strigolactones) from the host. In recent years, breeding crops for host-based resistance has been prioritized. However, such programs have not taken into account Striga’s ability to overcome host resistance. As a result, introduced resistance fails because of increased Striga virulence (infection severity). This article reviews technologies for a new paradigm in Striga resistance breeding that incorporates host resistance breeding with well-informed knowledge of parasite resistance in order to ensure durability of resistance.

Expanded Prader-Willi Syndrome due to an Unbalanced de novo Translocation t(14;15): Report and Review of the Literature

In the present study, we report a case of a female infant with a de novo unbalanced t(14;15) translocation resulting in a 14-Mb deletion of the 15q11.1q14 region. The deletion includes the 15q11.2q13 Prader-Willi syndrome (PWS) critical region, while no known deleted genes are found in the 14qter region. According to literature review, patients with similar or larger deletions in the 15q region exhibit an expanded phenotype of PWS with case-specific atypical features such as severe retardation, absence of speech, microcephaly, retrognathia, bifid uvula, ear malformations, and heart defects in addition to typical features of PWS. Our proband exhibited increased deep tendon reflexes, an atypical feature which is not reported in the reviewed literature. The severity of the phenotype is not directly associated with the size of the deletion; however, using a combination of methods, the identification of breakpoints and the deleted genes can be helpful for the prognostication in patients with atypical PWS deletions.

Retardasi Mental

Retardasi mental adalah penurunan fungsi intelektual yang menyeluruh secara bermaknadan secara langsung menyebabkan gangguan adaptasi sosial, dan bermanifestasi selamamasa perkembangan. Klasifikasi retardasi mental adalah mild retardation, moderateretardation, severe retardation dan profound retardation.Etiologi retardasi mental dapat terjadi mulai dari pranatal, perinatal dan postnatal.Beberapa penulis secara terpisah menyebutkan lebih dari 1000 macam penyebabterjadinya retardasi mental, dan banyak diantaranya yang dapat dicegah. Ditinjau daripenyebab secara langsung dapat digolongkan atas penyebab biologis dan psikososial.Diagnosis retardasi mental tidak hanya didasarkan atas uji intelegensia saja, melainkanjuga dari riwayat penyakit, laporan dari orangtua, laporan dari sekolah, pemeriksaanfisis, laboratorium, pemeriksaan penunjang.Tata laksana retardasi mental mencakup tatalaksana medis, penempatan di panti khusus,psikoterapi, konseling, dan pendidikan khusus. Pencegahan retardasi mental dapat primer(mencegah timbulnya retardasi mental), atau sekunder (mengurangi manifestasi klinisretardasi mental).

Ohtahara syndrome: Early infantile epileptic encephalopathy

DEFINITION Ohtahara syndrome (early infantile epileptic encephalopathy with suppression bursts), is the earliest developing form of epileptic encephalopathy. ETHIOLOGY It considered to be a result of static structural developing brain damage. CLINICAL PICTURE Variable seizures develop mostly within the first 10 days of life, but may occur during the first hour after delivery. The most frequently observed seizure type are epileptic spasms, which may be either generalized and symmetrical or lateralized. The tonic spasms may occur in clusters or singly, while awake and during sleep alike. The duration of spasms is up to 10 seconds, and the interval between spasms within cluster ranges from 9 to 15 seconds. In one third of cases, other seizure types include partial motor seizures or hemiconvulsions The disorder takes a progressively deteriorating course with increasing frequency of seizures and severe retardation of psychomotor development. DIAGNOSTIC WORKUP In the initial stage of Ohtahara syndrome, interictal EEG shows a pattern of suppression-burst with high-voltage paroxysmal discharges separated by prolonged periods of nearly flat tracing that last for up to 18 seconds. PROGNOSIS AND THREATMENT Half of the reported children having Ohtahara syndrome die in infancy. Anticonvulsant helps little in controlling the seizures and halting the deterioration of psychomotor development. Severe psychomotor retardation is the rule. With time, the disorder may evolve into West syndrome or partial epilepsy. Psychomotor development may be slightly better if the infants do not develop West and later Lennox-Gastaut syndrome.