Subject(s)
Breast Neoplasms/pathology , Nipples/pathology , Polyps/pathology , Pregnancy Complications, Neoplastic/pathology , Tuberous Sclerosis/complications , Adult , Breast Neoplasms/complications , Breast Neoplasms/diagnosis , Causality , Disease Susceptibility , Female , Humans , Polyps/complications , Polyps/diagnosis , Pregnancy , Pregnancy Complications, Neoplastic/diagnosisABSTRACT
Postsynaptic density (PSD) proteins have been implicated in the pathophysiology of neurodevelopmental and psychiatric disorders. Here, we present detailed clinical and genetic data for 20 patients with likely gene-disrupting mutations in TANC2-whose protein product interacts with multiple PSD proteins. Pediatric patients with disruptive mutations present with autism, intellectual disability, and delayed language and motor development. In addition to a variable degree of epilepsy and facial dysmorphism, we observe a pattern of more complex psychiatric dysfunction or behavioral problems in adult probands or carrier parents. Although this observation requires replication to establish statistical significance, it also suggests that mutations in this gene are associated with a variety of neuropsychiatric disorders consistent with its postsynaptic function. We find that TANC2 is expressed broadly in the human developing brain, especially in excitatory neurons and glial cells, but shows a more restricted pattern in Drosophila glial cells where its disruption affects behavioral outcomes.
Subject(s)
Mental Disorders/genetics , Nerve Tissue Proteins/metabolism , Neurodevelopmental Disorders/genetics , Proteins/genetics , Adolescent , Adult , Animals , Autistic Disorder/genetics , Autistic Disorder/psychology , Behavior, Animal , Brain/metabolism , Child , Child, Preschool , Craniofacial Abnormalities/genetics , Developmental Disabilities/genetics , Developmental Disabilities/psychology , Drosophila Proteins/genetics , Drosophila Proteins/metabolism , Drosophila melanogaster , Epilepsy/genetics , Female , Humans , Intellectual Disability/genetics , Intellectual Disability/psychology , Language Development Disorders/genetics , Language Development Disorders/psychology , Male , Membrane Proteins/genetics , Membrane Proteins/metabolism , Mental Disorders/psychology , Muscle Proteins/genetics , Muscle Proteins/metabolism , Mutation , Neurodevelopmental Disorders/psychology , Neuroglia/metabolism , Neurons/metabolism , Proteins/metabolism , Exome Sequencing , Young AdultSubject(s)
Muscular Diseases/complications , Muscular Diseases/genetics , Neuronal Ceroid-Lipofuscinoses/complications , Neuronal Ceroid-Lipofuscinoses/genetics , Female , Humans , Magnetic Resonance Imaging , Membrane Glycoproteins/genetics , Microscopy, Electron, Transmission , Molecular Chaperones/genetics , Muscular Diseases/diagnostic imaging , Mutation/genetics , Neuronal Ceroid-Lipofuscinoses/diagnostic imaging , Vacuoles/pathology , Vacuoles/ultrastructure , Young AdultABSTRACT
PURPOSE: The 22q13.3 deletion syndrome, also known as Phelan-McDermid syndrome, is a rare genetic disorder characterized by hypotonia, severely impaired development of speech and language, autistic-like behaviour, and minor dysmorphic features. Neurologic problems may include seizures of different types, such as febrile, generalized tonic-clonic, focal, and absence seizures. No peculiar EEG features have been associated with 22q13 deletion syndrome to date. In order to verify if a peculiar clinical and EEG pattern is present in 22q13.3 deletion syndrome, we studied six Italian patients with this chromosome abnormality. METHOD: Array CGH analysis was carried out in the six subjects (1 male, 5 females, age range 11-30 years, median 19.5). They underwent a complete general and neurologic examinations. The EEG study consisted of at least one awake and one nap-sleep video-EEG recordings and evaluation of other EEGs performed elsewhere. RESULTS: Three subjects suffered from myoclonic or generalized tonic-clonic seizures with a rather benign course; all showed multifocal paroxysmal abnormalities on EEG recording, predominant over the frontal-temporal regions, activated during sleep. CONCLUSION: 22q13.3 deletion syndrome seems to be associated, at least in a subgroup of patients, with a peculiar clinical and EEG pattern, characterized by a childhood epilepsy with a rather benign evolution and with multifocal paroxysmal EEG abnormalities activated by sleep.
Subject(s)
Brain Waves/physiology , Chromosome Disorders/complications , Seizures/etiology , Adolescent , Adult , Child , Chromosome Deletion , Chromosome Disorders/pathology , Chromosomes, Human, Pair 22 , Electroencephalography , Female , Humans , Italy , Male , Young AdultABSTRACT
We report the case of a girl with Cowden syndrome (CS) presenting with unilateral perisylvian dysplasia and with drug resistant focal seizures carrying a novel missense mutation 385G>A (G129R) in the PTEN gene. CS has been rarely reported in association with a cortical malformation or epilepsy. These cases suggest that cortical dysplasia needs to be suspected when a CS patient presents with drug-resistant seizures.
