Christine Soufflet

Mutational, functional, and expression studies of the TCF4 gene in Pitt-Hopkins syndrome.

Pitt‐Hopkins syndrome is a severe congenital encephalopathy recently ascribed to de novo heterozygous TCF4 gene mutations. We report a series of 13 novel PHS cases with a TCF4 mutation and show that EEG, brain magnetic resonance imagain (MRI), and immunological investigations provide valuable additional clues to the diagnosis. We confirm a mutational hot spot in the basic domain of the E‐protein. Functional studies illustrate that heterodimerisation of mutant TCF4 proteins with a tissue‐specific transcription factor is less effective than that homodimerisation in a luciferase reporter assay. We also show that the TCF4 expression pattern in human embryonic development is widespread but not ubiquitous. In summary, we further delineate an underdiagnosed mental retardation syndrome, highlighting TCF4 function during development and facilitating diagnosis within the first year of life. Hum Mutat 0, 1–8, 2009.

Epileptic phenotypes in children with respiratory chain disorders

Purpose:  Epilepsy is a commonly reported but rarely described clinical hallmark of mitochondrial respiratory chain defects (RCDs) with encephalopathy.

Clinical Evaluation of Ganaxolone in Pediatric and Adolescent Patients with Refractory Epilepsy

Summary:  Purpose: A pilot study of the safety, tolerability, dose range and potential efficacy of ganaxolone for the treatment of refractory epilepsy in pediatric and adolescent subjects.

A Gene for Pyridoxine-Dependent Epilepsy Maps to Chromosome 5q31

Pyridoxine-dependent epilepsy (PDE) is a rare autosomal recessive disorder characterized by generalized seizures in the first hours of life and responding only to pyridoxine hydrochloride. The pathogenesis of PDE is unknown, but an alteration in the binding of pyridoxal 5-phosphate to glutamic acid decarboxylase (GAD) has been postulated in patients with PDE. Results are reported for genetic linkage analyses in four families with consanguineous parents and in one family with nonconsanguineous parents. The GAD1 (2q31) and GAD2 genes (10p23) were tested and excluded. A genomewide search was subsequently performed, using microsatellite markers at an average distance of 10 cM, and the search revealed linkage of the disease-causing gene to markers on chromosome 5q31.2-q31.3 (maximum LOD score [Z(max)] 8.43 at recombination fraction [theta] 0 and Zmax=7.58 at straight theta=0 at loci D5S2017 and D5S1972, respectively). A recombination event, between loci D5S638 and D5S463, in one family defined the distal boundary, and a second recombination event between loci D5S2011 and D5S2017 in another family defined the proximal boundary of the genetic interval encompassing the PDE gene (5.1 cM). Ongoing studies may lead to the identification of the disease-causing gene.

Spectrum of epilepsy in terminal 1p36 deletion syndrome

Purpose: Previous reports have summarized the seizures types occurring in 1p36 deletion syndrome. To better define the spectrum of epilepsy, we studied 91 patients (median age 7.8 years) with confirmed 1p36 deletion.

Cryptogenic late-onset epileptic spasms: an overlooked syndrome of early childhood?

Summary:  Purpose: Few reports detailing late‐onset epileptic spasms have been published. To determine whether this condition merely represents a late variant of classic West syndrome or exhibits specific features distinct from the latter and related to a later stage of brain maturation, we analyzed the whole population with this specific seizure type, excluding symptomatic cases to avoid the effect of brain lesion.

Myoclonic absence epilepsy with photosensitivity and a gain of function mutation in glutamate dehydrogenase

Activating mutations in glutamate dehydrogenase (GDH), de novo or dominantly inherited, are responsible for the hyperinsulinism/hyperammonemia (HI/HA) syndrome. Epilepsy has been frequently reported in association with mutations in GDH, but the epilepsy phenotype has not been clearly determined. Here, we describe a family with a dominantly inherited mutation in GDH. The mother, brother and both sisters had myoclonic absence seizures, but only the mother and one sister had the complete HI/HA pattern. For the two sisters with myoclonic absences, epilepsy started during the second year of life while the brother, it started at 6 years. All 3 children showed the same EEG pattern characterized by photosensitive generalized and irregular spike-wave discharges and runs of multiple spikes. The mothers EEG recordings were normal without photosensitivity. Magnetic resonance imaging (MRI) and spectroscopy (MRS) were normal. A direct effect of the GDH mutation, perhaps in combination with recurrent hypoglycemia and chronic hyperammonemia could provide a pathophysiological explanation for the epilepsy observed in this syndrome and these are discussed.

Normal EEG in childhood: from neonates to adolescents.

The important EEG changes that occur throughout childhood are a major challenge for the neurophysiologist. These reflect brain maturation, which is especially fast during the first year of life. This article describes normal EEG features and variants, characteristic patterns of development, as well as some patterns that are unusual for age, from the neonatal period to adolescence. We also describe how to adapt techniques and prepare patients in order to get interpretable records of appropriate duration, in neonates, infants, and young children.

Epilepsy associated with shaken baby syndrome

ObjectThe shaken baby syndrome (SBS) is an important cause of developmental delay in infants. Epileptic seizures are a common feature of this syndrome. The aim if this study is to analyse the impact of the early and late seizures disorder.Materials and methodsWe have retrospectively reviewed the clinical and electrophysiological findings in a series of 404 children hospitalised with SBS.ResultsIn the acute phase, clinical epileptic seizures of various semiologies were found in 73% of the infants. Only 11% of the children had a normal EEG on admission. A poor outcome was found in 88% of the children in case of persisting EEG anomalies despite anti-epileptic treatment with 48% mortality in these patients. The development of refractory epilepsy was also associated with a poor outcome in this series. In fact 96% of the children with seizure recurrence had behavioural problems.ConclusionsThe early recognition and subsequent management of these seizures is vital to prevent further neurological injury. Delayed or recurrent epileptic seizures may occur with a different semiology to the seizures in the acute phase and are also associated with a poor prognosis.

The Nonmalformed Hemisphere Is Secondarily Impaired in Young Children with Hemimegalencephaly: A Pre‐ and Postsurgery Study with SPECT and EEG

Summary:  Purpose: To study separately the functional value of each cerebral hemisphere in hemimegalencephaly (HME). HME is a unique model of unilateral hemispheric lesion, but one suspects that the non‐HME hemisphere also could be functionally impaired because the postsurgery outcome is less favorable than expected.