ABSTRACT
Kabuki syndrome (KS) is a rare genetic disease that causes developmental delay and congenital anomalies. Since the identification of MLL2 mutations as the primary cause of KS, such mutations have been identified in 56%-76% of affected individuals, suggesting that there may be additional genes associated with KS. Here, we describe three KS individuals with de novo partial or complete deletions of an X chromosome gene, KDM6A, that encodes a histone demethylase that interacts with MLL2. Although KDM6A escapes X inactivation, we found a skewed X inactivation pattern, in which the deleted X chromosome was inactivated in the majority of the cells. This study identifies KDM6A mutations as another cause of KS and highlights the growing role of histone methylases and histone demethylases in multiple-congenital-anomaly and intellectual-disability syndromes.
Subject(s)
Abnormalities, Multiple/genetics , DNA-Binding Proteins/metabolism , Gene Deletion , Hematologic Diseases/genetics , Histone Demethylases/genetics , Neoplasm Proteins/metabolism , Nuclear Proteins/genetics , Vestibular Diseases/genetics , Abnormalities, Multiple/metabolism , Adolescent , Base Sequence , Child, Preschool , Chromosomes, Human, X/genetics , Developmental Disabilities/genetics , Face/abnormalities , Female , Hematologic Diseases/metabolism , Histone Demethylases/metabolism , Humans , Infant , Intellectual Disability/genetics , Male , Molecular Sequence Data , Nuclear Proteins/metabolism , Vestibular Diseases/metabolismABSTRACT
Perioral myoclonia with absences belongs to the "idiopathic generalised epilepsy syndromes in development", currently not yet cited in the ILAE classification. This epilepsy syndrome is associated with a seizure type that appears to be specific. Here, we report polygraphic recordings of this seizure type in a young boy, previously misdiagnosed with focal epilepsy. EEG and clinical features were useful to differentiate diagnosis of his seizures from other absence or myoclonic seizures. Interestingly, some seizures were associated with neck myoclonia. Home video recording of myoclonic status aggravated by inappropriate treatment is also presented. [Published with video sequences].
Subject(s)
Anticonvulsants/adverse effects , Carbamazepine/analogs & derivatives , Epilepsies, Myoclonic/chemically induced , Epilepsies, Myoclonic/physiopathology , Epilepsy, Absence/chemically induced , Epilepsy, Absence/physiopathology , Brain/pathology , Carbamazepine/adverse effects , Child , Electroencephalography , Humans , Levetiracetam , Magnetic Resonance Imaging , Male , Oxcarbazepine , Piracetam/analogs & derivatives , Piracetam/therapeutic useABSTRACT
This report illustrates the usefulness and safety of very early hemispherotomy in an infant with Ohtahara syndrome (OS) secondary to left parieto-occipital megalencephaly. It provides evidence that surgical intervention might provide promising results in selected cases, and that young age is not a contraindication for this type of surgery.
Subject(s)
Brain Diseases/pathology , Brain Diseases/surgery , Epilepsy/pathology , Epilepsy/surgery , Hemispherectomy , Occipital Lobe/pathology , Occipital Lobe/surgery , Parietal Lobe/pathology , Parietal Lobe/surgery , Brain Diseases/diagnostic imaging , Child Development , Electroencephalography , Female , Humans , Infant , Magnetic Resonance Imaging , Occipital Lobe/diagnostic imaging , Parietal Lobe/diagnostic imaging , Positron-Emission Tomography , Syndrome , Treatment OutcomeABSTRACT
This study was undertaken to determine the effect of antiepileptic treatment on a child with attention-deficit-hyperactivity disorder and subclinical electroencephalographic discharges without seizures. We performed a longitudinal follow-up study correlating clinical, neuropsychologic, and electroencephalographic features with antiepileptic drug therapy. The results revealed a temporal relation between subclinical epileptiform discharges and cognitive dysfunction and a significant effectiveness of antiepileptic drugs on attention-deficit-hyperactivity disorder and electroencephalographic discharges. The practice of monitoring antiepileptic treatment limited to seizure control should be revised; cognitive impairments also need to be taken into account even without occurrence of seizure. The classical principle of treating only seizures needs to be reconsidered.
Subject(s)
Attention Deficit Disorder with Hyperactivity/physiopathology , Cognition Disorders/physiopathology , Electroencephalography , Epilepsy/physiopathology , Antiemetics/pharmacology , Antiemetics/therapeutic use , Attention Deficit Disorder with Hyperactivity/drug therapy , Attention Deficit Disorder with Hyperactivity/psychology , Child , Child, Preschool , Cognition Disorders/drug therapy , Cognition Disorders/psychology , Electroencephalography/drug effects , Electroencephalography/statistics & numerical data , Epilepsy/drug therapy , Epilepsy/psychology , Female , Follow-Up Studies , HumansABSTRACT
Central nervous system (CNS) dysfunction is a cardinal feature in 22q11 deletion. The underlying CNS abnormalities remain, however, unknown. We report unilateral hemispheric polymicrogyria in a child with 22q11 deletion presenting with hemiplegia and cognitive and behavioural disorders. This observation widens the spectrum of brain malformations associated with this genetic defect. It further suggests a relationship between the 22q11 deletion and disorders of cerebral gyration. It would therefore be interesting to look for neuronal migration disorders in patients with 22q11 deletion presenting neurological signs, and on the other hand to screen for 22q11 deletion in patients with isolated neuronal migration disorders.
