"DOOR syndrome"

DOORS syndrome and a recurrent truncating ATP6V1B2 variant. Biallelic variants in TBC1D24, which encodes a protein that regulates vesicular transport, are frequently identified in patients with DOORS (deafness, onychodystrophy, osteodystrophy, intellectual disability [previously referred to as mental retardation], and seizures) syndrome. The aim of the study was to identify a genetic cause in families with DOORS syndrome and without a TBC1D24 variant. Exome or Sanger sequencing was performed in individuals with a clinical diagnosis of DOORS syndrome without TBC1D24 variants. We identified the same truncating variant in ATP6V1B2 (NM_001693.4:c.1516C>T; p.Arg506*) in nine individuals from eight unrelated families with DOORS syndrome. This variant was already reported in individuals

DOOR syndrome: A case report and its embryological basis. DOOR syndrome is an extremely rare genetic disorder. "DOOR″ is an acronym to describe the combination of: deafness, onychodystrophy, osteodystrophy and mental retardation. We present a patient, with all of the above-mentioned main symptoms, that was rehabilitated with convencional hearing aids. The presented case suggested that every case of deafness and abnormal nails and phalanges in the hands and feet should have a clinical diagnosis of possible DOOR syndrome. Based on embryological process, congenital abnormal nails or phalanges highlights the importance for detailed hearing screening.

The genetic basis of DOORS syndrome: an exome-sequencing study. Deafness, onychodystrophy, osteodystrophy, mental retardation, and seizures (DOORS) syndrome is a rare autosomal recessive disorder of unknown cause. We aimed to identify the genetic basis of this syndrome by sequencing most coding exons in affected individuals. Through a search of available case studies and communication with collaborators, we identified families that included at least one individual with at least three of the five main features of the DOORS syndrome: deafness, onychodystrophy, osteodystrophy, intellectual disability, and seizures. Participants were recruited from 26 centres in 17 countries. Families described in this study were enrolled between Dec 1, 2010, and March 1, 2013. Collaborating physicians enrolling

that the RAB-specific GTPase-activating protein TBC1D24 controls the endosomal trafficking of the synaptic vesicles (SVs) in Drosophila and mammalian neurons, and mutations in TBC1D24 may lead to non-syndromic hearing loss or hearing loss associated with the DOORS syndrome in humans. In this study, we generated a knock-in mouse model for the p. S178L mutation in TBC1D24, which leads to autosomal dominant non

health services and community mental health teams. There is, however, a small but important minority of people who live with schizophrenia whose recovery is harder to achieve and who require a specialist service (Box 4). Many individuals with rehabilitation needs have significant histories of repeat or protracted acute hospital admissions (sometimes called ‘revolving door syndrome’). Acute ward

of ACT, client trajectories would generally involve long-stay hospitalization, acute-care revolving-door syndrome, and/or homelessness. Recommendations: 1. Psychosocial treatments should be integrated into mental health care service provision in both the inpatient and outpatient sector. Family intervention, psychoeducation, social skills training, and residential care should all be prioritized. Other

of the affected individuals have global developmental and/or intellectual delay, all had seizures, two had polymicrogyria, and four had a peripheral neuropathy. Eight children passed away before four years old. Two of them had a clinical diagnosis of DOORS syndrome (deafness, onychodystrophy, osteodystrophy, mental retardation, and seizures), a condition that includes sensorineural deafness, shortened terminal phalanges with small finger and toenails, intellectual disability, and seizures; this condition overlaps with the severe phenotypes associated with inherited GPI deficiency. Most individuals tested showed elevated alkaline phosphatase, which is a characteristic of the inherited GPI deficiency but not DOORS syndrome. It is notable that two severely affected individuals showed 2-oxoglutaric aciduria, which

had strabismus. The deletion was absent in all 13 parents who were available for testing. The area of overlap encompasses seven genes including TBC1D24, ATP6V0C, and PDPK1 (also known as PDK1). Bi-allelic TBC1D24 pathogenic variants are known to cause nonsyndromic deafness, epileptic disorders, or DOORS syndrome (deafness, onychodystrophy, osteodystrophy, mental retardation, seizures). Sanger

cases consisted of epilepsy of infancy with migrating focal seizures, 2 with progressive myoclonus epilepsies, 1 with Dravet syndrome, 1 with DOORS syndrome, and 3 with unclassified epileptic encephalopathy. The clinical feature of TBC1D24 gene mutation related epilepsy was focal myoclonus, and tended to develop into myoclonic status epilepticus, and could be aggravated by infections, and terminated

Case Report: Novel mutations in TBC1D24 are associated with autosomal dominant tonic-clonic and myoclonic epilepsy and recessive Parkinsonism, psychosis, and intellectual disability Mutations disrupting presynaptic protein TBC1D24 are associated with a variable neurological phenotype, including DOORS syndrome, myoclonic epilepsy, early-infantile epileptic encephalopathy, and non-syndromic

), epilepsy (OMIM 605021), epilepsy with deafness, or DOORS syndrome (OMIM 220500) that is characterized by deafness, onychodystrophy (alteration of toenail or fingernail morphology), osteodystrophy (defective development of bone), mental retardation, and seizures. A comprehensive understanding of the multifaceted roles of each gene associated with human deafness is expected to provide future opportunities

, ptosis, blepharophimosis, hypertelorism, cleft palate, multiple renal cysts, absent nails, small or absent terminal phalanges, absent speech and intellectual disability. Syndromes that were initially considered include DOORS syndrome, Coffin-Siris syndrome and Dubowitz syndrome. Clinical investigations coupled with karyotype analysis, array-comparative genomic hybridization, exome and Sanger sequencing were performed to characterize the condition in this child. Sanger sequencing was negative for the DOORS syndrome gene TBC1D24 but exome sequencing identified a homozygous deletion in UBE3B (NM_183415:c.3139_3141del, p.1047_1047del) located within the terminal portion of the HECT domain. This finding coupled with the presence of characteristic features such as brachycephaly, ptosis, blepharophimosis

to hospital to be discharged to the community under close supervision. CTOs are intended to reduce the ‘revolving-door syndrome’ of frequent readmissions for treatment-resistant patients by imposing conditions on their community care. Individuals who break these conditions can be brought back to hospital for up to 72 hours while the relevant clinician decides what to do next.CTOs were introduced following

(mental retardation) who presented with seizures in the emergency department. General examination revealed dysmorphic features like anonychia, low set ears, long philtrum, large lower lips and abnormal dermatoglyphics with features of osteodystrophy on radiology. She was diagnosed as a case of DOORS syndrome, an extremely rare genetic condition affecting the TCA cycle, with just over 40 cases reported , worldwide till date, since its first description in 1961. Her genetic analysis did not reveal the common TBC1D24 mutation in 16p13.3 resulting often from substitutions affecting the arginine at position 242, in spite of all classical clinical features associated with it, suggesting genetic heterogeneity in DOORS syndrome. Though four year follow-up revealed changes in seizure pattern, there was no optic

with a panoply of clinical symptoms including autosomal recessive NSHL, syndromic hearing impairment associated with onychodystrophy, osteodystrophy, mental retardation, and seizures (DOORS syndrome), and a wide range of epileptic disorders.

DOOR syndrome: deficiency of E1 component of the 2-oxoglutarate dehydrogenase complex. Four patients from three families with the clinical features of DOOR syndrome (onycho-osteodystrophy, dystrophic thumbs, sensorineural deafness, and increased urinary levels of 2-oxoglutarate) are the subjects of this report. Our report deals with the autosomal recessive form of the disease, wherein the activity of 2-oxoglutarate decarboxylase (E1(0)) in fibroblasts and white blood cells of the patients is decreased. The activity of E1(0) in all patients' fibroblasts and white blood cells was significantly lower compared to the controls. This study demonstrates for the first time that E1(0) deficiency is an important biochemical marker for the autosomal recessive form of DOOR syndrome.

Reducing recidivism: medication versus psychosocial rehabilitation. 1. Noncompliance with psychotropic medications is a primary reason for recidivism to inpatient hospitalization. It is a great contributor to the "Revolving door syndrome." 2. Psychosocial rehabilitation clubhouses can decrease inpatient hospitalization in patients with chronic mental illness. Their supportive, vocational