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Muscle & Nerve Dec 2013
Topics: Amyotrophic Lateral Sclerosis; Humans; Male; Middle Aged; Mobius Syndrome; Superoxide Dismutase; Superoxide Dismutase-1
PubMed: 23873540
DOI: 10.1002/mus.23958 -
Brazilian Journal of Anesthesiology... 2013Malignant hyperthermia (MH) is a pharmacogenetic skeletal muscle disorder characterized by a hypermetabolic state after anesthesia with succinylcholine and/ or volatile...
BACKGROUND AND OBJECTIVES
Malignant hyperthermia (MH) is a pharmacogenetic skeletal muscle disorder characterized by a hypermetabolic state after anesthesia with succinylcholine and/ or volatile anesthetics. Various neuromuscular syndromes are associated with susceptibility; however, Moebius syndrome has not been reported. Dantrolene is the drug of choice for treatment. Recurrence may occur in up to 20% of cases after the initial event treatment.
CASE REPORT
Male infant, fi rst twin, 7 months old, weighing 6.5kg and presenting with Moebius syndrome was admitted for clubfoot repair. The patient had MH after exposure to sevoflurane and succinylcholine, which was readily reversed with dantrolene maintained for 24 hours. Ten hours after dantrolene discontinuation, there was recrudescence of MH that did not respond satisfactorily to treatment, and the patient died.
DISCUSSION
Musculoskeletal disorders in children are associated with increased risk of developing MH, although Moebius syndrome has not yet been reported. Dantrolene is the drug of choice for treating this syndrome; prophylaxis is indicated during the fi rst 24-48 hours of the episode onset. The main risk factors for recurrence are muscular type, long latency after anesthetic exposure, and increased temperature. The child had only one risk factor. This case leads us to reflect on how we must be attentive to children with musculoskeletal disease and maintain treatment for 48 hours.
Topics: Disease Progression; Fatal Outcome; Humans; Infant; Male; Malignant Hyperthermia; Mobius Syndrome
PubMed: 23683455
DOI: 10.1016/S0034-7094(13)70234-4 -
PloS One 2013Reverse simulation models of facial expression recognition suggest that we recognize the emotions of others by running implicit motor programmes responsible for the...
Reverse simulation models of facial expression recognition suggest that we recognize the emotions of others by running implicit motor programmes responsible for the production of that expression. Previous work has tested this theory by examining facial expression recognition in participants with Möbius sequence, a condition characterized by congenital bilateral facial paralysis. However, a mixed pattern of findings has emerged, and it has not yet been tested whether these individuals can imagine facial expressions, a process also hypothesized to be underpinned by proprioceptive feedback from the face. We investigated this issue by examining expression recognition and imagery in six participants with Möbius sequence, and also carried out tests assessing facial identity and object recognition, as well as basic visual processing. While five of the six participants presented with expression recognition impairments, only one was impaired at the imagery of facial expressions. Further, five participants presented with other difficulties in the recognition of facial identity or objects, or in lower-level visual processing. We discuss the implications of our findings for the reverse simulation model, and suggest that facial identity recognition impairments may be more severe in the condition than has previously been noted.
Topics: Adult; Computer Simulation; Emotions; Facial Expression; Female; Humans; Male; Middle Aged; Mobius Syndrome; Models, Anatomic; Pattern Recognition, Visual; Reproducibility of Results
PubMed: 23638131
DOI: 10.1371/journal.pone.0062656 -
Behavioral and Brain Functions : BBF Feb 2013We report on a 6-year-old Turkish boy with profound sensorineural deafness, balance disorder, severe disorder of oral motor function, and mild developmental delay....
BACKGROUND
We report on a 6-year-old Turkish boy with profound sensorineural deafness, balance disorder, severe disorder of oral motor function, and mild developmental delay. Further findings included scaphocephaly, plagiocephaly, long palpebral fissures, high narrow palate, low-set posteriorly rotated ears, torticollis, hypoplastic genitalia and faulty foot posture. Parents were consanguineous.
METHODS AND RESULTS
Computed tomography and magnetic resonance imaging showed bilateral single widened cochlear turn, narrowing of the internal auditory canal, and bilateral truncation of the vestibulo-cochlear nerve. Microarray analysis and next generation sequencing showed a homozygous deletion of chromosome 5q31.1 spanning 115.3 kb and including three genes: NEUROG1 (encoding neurogenin 1), DCNP1 (dendritic cell nuclear protein 1, C5ORF20) and TIFAB (TIFA-related protein). The inability to chew and swallow, deafness and balance disorder represented congenital palsies of cranial nerves V (trigeminal nerve) and VIII (vestibulo-cochlear nerve) and thus a congenital cranial dysinnervation disorder.
CONCLUSIONS
Based on reported phenotypes of neurog1 null mutant mice and other vertebrates, we strongly propose NEUROG1 as the causative gene in this boy. The human NEUROG1 resides within the DFNB60 locus for non-syndromic autosomal recessive deafness on chromosome 5q22-q31, but linkage data have excluded it from being causative in the DFNB60 patients. Given its large size (35 Mb, >100 genes), the 5q22-q31 area could harbor more than one deafness gene. We propose NEUROG1 as a new gene for syndromic autosomal recessive hearing loss and congenital cranial dysinnervation disorder including cranial nerves V and VIII.
Topics: Basic Helix-Loop-Helix Transcription Factors; Child; Chromosome Mapping; Consanguinity; DNA Mutational Analysis; Gene Deletion; Genome-Wide Association Study; Humans; Karyotyping; Magnetic Resonance Imaging; Male; Microarray Analysis; Mobius Syndrome; Nerve Tissue Proteins; Neurologic Examination; Polymerase Chain Reaction; Skull; Tomography, X-Ray Computed
PubMed: 23419067
DOI: 10.1186/1744-9081-9-7 -
Brain : a Journal of Neurology Feb 2013
Topics: Amino Acid Substitution; Female; Genes, Overlapping; Humans; Kallmann Syndrome; Lissencephaly; Male; Malformations of Cortical Development; Mobius Syndrome; Mutation; Neurons; Tubulin; Vomiting
PubMed: 23413256
DOI: 10.1093/brain/awt001 -
Brain : a Journal of Neurology Feb 2013Missense mutations in TUBB3, the gene that encodes the neuronal-specific protein β-tubulin isotype 3, can cause isolated or syndromic congenital fibrosis of the...
Missense mutations in TUBB3, the gene that encodes the neuronal-specific protein β-tubulin isotype 3, can cause isolated or syndromic congenital fibrosis of the extraocular muscles, a form of complex congenital strabismus characterized by cranial nerve misguidance. One of the eight TUBB3 mutations reported to cause congenital fibrosis of the extraocular muscles, c.1228G>A results in a TUBB3 E410K amino acid substitution that directly alters a kinesin motor protein binding site. We report the detailed phenotypes of eight unrelated individuals who harbour this de novo mutation, and thus define the 'TUBB3 E410K syndrome'. Individuals harbouring this mutation were previously reported to have congenital fibrosis of the extraocular muscles, facial weakness, developmental delay and possible peripheral neuropathy. We now confirm by electrophysiology that a progressive sensorimotor polyneuropathy does indeed segregate with the mutation, and expand the TUBB3 E410K phenotype to include Kallmann syndrome (hypogonadotropic hypogonadism and anosmia), stereotyped midface hypoplasia, intellectual disabilities and, in some cases, vocal cord paralysis, tracheomalacia and cyclic vomiting. Neuroimaging reveals a thin corpus callosum and anterior commissure, and hypoplastic to absent olfactory sulci, olfactory bulbs and oculomotor and facial nerves, which support underlying abnormalities in axon guidance and maintenance. Thus, the E410K substitution defines a new genetic aetiology for Moebius syndrome, Kallmann syndrome and cyclic vomiting. Moreover, the c.1228G>A mutation was absent in DNA from ∼600 individuals who had either Kallmann syndrome or isolated or syndromic ocular and/or facial dysmotility disorders, but who did not have the combined features of the TUBB3 E410K syndrome, highlighting the specificity of this phenotype-genotype correlation. The definition of the TUBB3 E410K syndrome will allow clinicians to identify affected individuals and predict the mutation based on clinical features alone.
Topics: Adolescent; Adult; Amino Acid Substitution; Child; Female; Humans; Kallmann Syndrome; Male; Mobius Syndrome; Mutation, Missense; Neurons; Pedigree; Tubulin; Vomiting; Young Adult
PubMed: 23378218
DOI: 10.1093/brain/aws345 -
Indian Journal of Ophthalmology 2012We report a case of an 18-year-old male who presented with watering and inability to close the left eye completely since 6 months and inability to move both eyes outward...
We report a case of an 18-year-old male who presented with watering and inability to close the left eye completely since 6 months and inability to move both eyes outward and to close the mouth since childhood. Ocular, facial, and systemic examination revealed that the patient had bilateral complete lateral rectus and bilateral incomplete medial rectus palsy, left-sided facial nerve paralysis, thickening of lower lip and inability to close the mouth, along with other common musculoskeletal abnormalities. This is a typical presentation of Moebius syndrome which is a very rare congenital neurological disorder characterized by bilateral facial and abducens nerve paralysis. This patient had bilateral incomplete medial rectus palsy which is suggestive of the presence of horizontal gaze palsy or occulomotor nerve involvement as a component of Moebius sequence.
Topics: Adolescent; Eye Movements; Humans; Male; Mobius Syndrome; Rare Diseases; Strabismus; Visual Acuity
PubMed: 23202399
DOI: 10.4103/0301-4738.103798 -
Ciencia & Saude Coletiva Jul 2012This article puts into perspective the controversy between the association of the use of misoprostol for abortion and teratogenicity studies of the type found in a case...
This article puts into perspective the controversy between the association of the use of misoprostol for abortion and teratogenicity studies of the type found in a case report. The use of herbal medicinal drugs and the medical-obstetric and national and international norms governing the registration and circulation of pharmaceutical products were examined. Official documents of ANVISA, the Ministry of Health and the World Health Organization on the use of misoprostol, as well as 68 articles such as case reports published in national journals, linking abortion, misoprostol and teratogenicity were reviewed, systematically filed and analyzed using the monographic method. The legal prohibition of abortion prevents the proper prescription and use of a drug such as misoprostol that is both safe and effective. Thus, the danger for the health of women is linked not to the intrinsic characteristics of the drug, but to the moral arguments that constitute negligence and disregard for the fundamental rights of women.
Topics: Abortifacient Agents, Nonsteroidal; Abortion, Criminal; Abortion, Induced; Female; Humans; Misoprostol; Mobius Syndrome; Pregnancy
PubMed: 22872339
DOI: 10.1590/s1413-81232012000700016 -
Arquivos Brasileiros de Oftalmologia 2012To compare the profiles and clinical findings of a series of patients with Möbius sequence from Brazil with a series from Italy.
PURPOSE
To compare the profiles and clinical findings of a series of patients with Möbius sequence from Brazil with a series from Italy.
METHODS
This is a multicenter study, which includes 46 Möbius sequence patients from Brazil and 20 from Italy. Socio-demographic, gestational, and neonatal profile characteristics were collected from interviews with the guardians of the Möbius sequence patients and compared. The Möbius sequence patients were submitted to an ophthalmologic examination and systemic malformations were also evaluated.
RESULTS
Misoprostol was used in the first trimester of pregnancy by 26 (56.5%) of the mothers of the Möbius sequence patients in the Brazilian series and was not used by any of the Italian mothers. The mean age of the Brazilian Möbius sequence patients was 89.95 ± 7.79 months and the mean age of the Italian patients was 102.6 ± 22.94 months (P=0.6105; Mann-Whitney test). Brazilian mothers had a significantly lower education level (P=0.0002; Fisher's exact test) and Italian mothers had significantly more stable relationships (p=0.0002; Fisher's exact test). The frequency of ocular and systemic abnormalities was similar in both series.
CONCLUSION
Adverse events during pregnancy varied between both groups. A history of misoprostol use during early pregnancy was present only in Brazilian mothers, who had lower levels of education and less frequent stable marital statuses. Clinical findings were similar between both groups of patients.
Topics: Abortifacient Agents, Nonsteroidal; Adolescent; Adult; Brazil; Child; Child, Preschool; Cross-Sectional Studies; Eye Diseases; Female; Gestational Age; Humans; Infant; Italy; Male; Misoprostol; Mobius Syndrome; Pregnancy; Pregnancy Complications; Prospective Studies; Socioeconomic Factors; Statistics, Nonparametric; Young Adult
PubMed: 22872205
DOI: 10.1590/s0004-27492012000300011 -
American Journal of Human Genetics Jul 2012Members of the highly conserved homeobox (HOX) gene family encode transcription factors that confer cellular and tissue identities along the antero-posterior axis of...
Members of the highly conserved homeobox (HOX) gene family encode transcription factors that confer cellular and tissue identities along the antero-posterior axis of mice and humans. We have identified a founder homozygous missense mutation in HOXB1 in two families from a conservative German American population. The resulting phenotype includes bilateral facial palsy, hearing loss, and strabismus and correlates extensively with the previously reported Hoxb1(-/-) mouse phenotype. The missense variant is predicted to result in the substitution of a cysteine for an arginine at amino acid residue 207 (Arg207Cys), which corresponds to the highly conserved Arg5 of the homeodomain. Arg5 interacts with thymine in the minor groove of DNA through hydrogen bonding and electrostatic attraction. Molecular modeling and an in vitro DNA-protein binding assay predict that the mutation would disrupt these interactions, destabilize the HOXB1:PBX1:DNA complex, and alter HOXB1 transcriptional activity.
Topics: Animals; Base Sequence; Child; Child, Preschool; Facial Paralysis; Female; Founder Effect; Hearing Loss, Sensorineural; Homeodomain Proteins; Humans; Male; Mice; Mobius Syndrome; Models, Molecular; Mutation, Missense; Pedigree; Phenotype; Strabismus; Transcription, Genetic; Transcriptional Activation
PubMed: 22770981
DOI: 10.1016/j.ajhg.2012.05.018