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A heterozygous gain‐of‐function variant in the acyl‐CoA oxidase 1 (ACOX1) gene, c.710A>G (p.Asn237Ser), is known to cause Mitchell syndrome, a very rare progressive disorder characterized by episodic demyelination, sensory polyneuropathy, and hearing loss. Only eight patients have been described so far. A single patient has been treated with intravenous immunoglobulin administration, indicating clinical improvement. In this study, we describe a 10‐year‐old girl carrying the identical mutation, who presented with progressive sensorineural deafness, visual abnormalities, skin ichthyosis, and gait ataxia from infantile age with progressive worsening and loss of walking ability by the age of 10 years. Antioxidant therapies and monthly intravenous immunoglobulin infusions showed excellent clinical results: after 1 year of treatment, the child is now able to walk, run, and jump. We emphasize the importance of early genetic diagnosis since an effective treatment is available for this rare condition. [ABSTRACT FROM AUTHOR]

We present these two cases to emphasize the necessity of critical thinking and high suspicion of the disease (Rogers syndrome) to avoid potentially fatal situations due to its rarity and the importance of early treatment. [ABSTRACT FROM AUTHOR]

Congenital cranial dysinnervation disorders (CCDDs) are a heterogeneous group of neurodevelopmental phenotypes caused by a primary disturbance of innervation due to deficient, absent, or misguided cranial nerves. Although some CCDDs genes are known, several clinical phenotypes and their aetiologies remain to be elucidated. We describe a 12‐year‐old boy with hypotonia, developmental delay, sensorineural hearing loss, and keratoconjunctivitis due to lack of corneal reflex. He had a long expressionless face, severe oromotor dysfunction, bilateral agenesis/severe hypoplasia of the VIII nerve with marked atresia of the internal auditory canals and cochlear labyrinth malformation. Trio‐exome sequencing identified a homozygous loss of function variant in the NEUROG1 gene (NM_006161.2: c.202G > T, p.Glu68*). NEUROG1 is considered a causal candidate for CCDDs based on (i) the previous report of a patient with a homozygous gene deletion and developmental delay, deafness due to absent bilateral VIII nerves, and severe oromotor dysfunction; (ii) a second patient with a homozygous NEUROG1 missense variant and corneal opacity, absent corneal reflex and intellectual disability; and (iii) the knockout mouse model phenotype which highly resembles the disorder observed in humans. Our findings support the growing compelling evidence that loss of NEUROG1 leads to a very distinctive disorder of cranial nerves development. [ABSTRACT FROM AUTHOR]

Autosomal dominant hypoparathyroidism, deafness, and renal dysplasia (HDR) syndrome are typically diagnosed by manifestations of the three features with a positive family history. Our case carried a de novo variant in causative gene, GATA3, but presenting no renal dysplasia or family history. The phenotypic heterogeneity raises a caution for diagnosis. [ABSTRACT FROM AUTHOR]

Bi‐allelic HOXA1 pathogenic variants clinically manifest as two distinct syndromes, Bosley–Salih–Alorainy syndrome (BSAS) and Athabascan brainstem dysgenesis syndrome, mainly reported in two different populations from Saudi Arabia and southwest North America, respectively. Here we report two siblings of Indian origin with BSAS phenotype caused by a novel homozygous exon 2 HOXA1 pathogenic variants. [ABSTRACT FROM AUTHOR]

Background: Barakat syndrome is an autosomal dominant disorder characterized by the triad of hypoparathyroidism, sensorineural deafness, and renal anomalies and is caused by mutations in GATA3 gene. SLC34A3 is the cause gene of hypophosphatemic rickets with hypercalciuria, and heterozygous carriers may have milder clinical symptoms. The aim of this study was to identify the underlying genetic cause of a patient who initially presented with renal failure, hypercalciuria, kidney stone, and bilateral sensorineural deafness. Methods: A 6‐year‐old boy with complex clinical presentations was investigated. Comprehensive medical evaluations were performed including auditory function tests, endocrine function tests, metabolic studies, and imaging examinations. Molecular diagnoses were analyzed by trio whole‐exome sequencing. Results: One novel de novo deleterious variant (c. 324del) of the GATA3 gene was identified in the patient. The patient can be diagnosed with Barakat syndrome. In addition, one novel variant (c. 589A>G) of the SLC34A3 gene was detected, which was inherited from the father. This heterozygous variant can explain the hypercalciuria and kidney stone that occurred in both the patient and his father. Conclusion: This study provides a special case which is phenotype‐driven dual diagnoses, and the two novel variants can parsimoniously explain the complex clinical presentations of this patient. [ABSTRACT FROM AUTHOR]

Vohwinkel syndrome (VS) is a rare autosomal dominant condition, also known as mutilating palmoplantar keratoderma accompanied by sensorineural deafness. The LOR and GJB2 genes are reported to be responsible for VS. The GJB2 gene encodes connexin 26, a component of intercellular gap junctions expressed in various tissues. We report the case of a 31‐year‐old Chinese woman with classic VS characterized by sensorineural deafness and mutilating palmoplantar keratoderma. Further genetic studies demonstrated a nucleotide change (c.175G>A) in the GJB2 gene, leading to an amino acid alteration (G59S). This identical missense mutation (G59S) has also been reported in a patient with Bart–Pumphrey syndrome. Together with our findings and previous studies, we conclude that the identical mutation (G59S) in the GJB2 gene contributes to various manifestations. [ABSTRACT FROM AUTHOR]

EAST (Epilepsy, Ataxia, Sensorineural deafness, Tubulopathy) or SeSAME (Seizures, Sensorineural deafness, Ataxia, Mental retardation, and Electrolyte imbalance) syndrome is a rare autosomal recessive syndrome first described in 2009 independently by Bockenhauer and Scholl. It is caused by mutations in KCNJ10, which encodes Kir4.1, an inwardly rectifying K+ channel found in the brain, inner ear, kidney and eye. To date, 16 mutations and at least 28 patients have been reported. In this paper, we review mutations causing EAST/SeSAME syndrome, clinical manifestations in detail, and efficacy of treatment in previously reported patients. We also report a new Latvian kindred with 4 patients. In contrast to the majority of previous reports, we found a progressive course of the disorder in terms of hearing impairment and neurologic deficit. The treatment is based on antiepileptic drugs, electrolyte replacement, hearing aids and mobility devices. Future research should concentrate on recognizing the lesions in the central nervous system to evaluate new potential diagnostic criteria and on formally evaluating intellectual disability. [ABSTRACT FROM AUTHOR]

TUTAR, E.,et al.: Assessment of Ventricular Repolarization in a Large Group of Children with Early Onset DeafnessThis study examined the ECG traces of 397 deaf children (age 12.5± 2.9 years, range 6–19 years), after exclusion of cases with Jervell and Lange-Nielsen syndrome (JLNS), and compared them to those of 361 normal hearing counterparts (age 12.5± 2.7 years; range 7–18 years). An observer, who was unaware of the hearing status of the subjects, measured QT and QTc intervals and calculated dispersions of QT and QTc from standard 12-lead ECGs recorded at a speed of 25 mm/s at rest. Although the mean QT was found to be longer in deaf children than that observed in the control group (P<0.0001), the mean QTc was significantly shorter (P<0.0001). The mean heart rate was significantly lower in deaf children. When QT and QTc data were recompared after the children were grouped according to the heart rate, the observed difference became less significant or disappeared. In conclusion, there are no major abnormalities for repolarization parameters in children with congenital sensorineural deafness, when compared to hearing counterparts, if heart rates are similar. Based on these results, routine ECG screening of deaf children for repolarization abnormalities may be unnecessary unless they have a history of syncope or positive family history of syncope and/or early sudden death.(PACE 2004; 27:1217–1220) [ABSTRACT FROM AUTHOR]

Hearing loss in patients with X-linked agammaglobulinemia is often attributed to recurrent infections. However, recent genetic studies suggest a different etiology in some patients. We present three unrelated patients, 6, 9, and 14 years of age, with large deletions of the terminal portion of the Bruton tyrosine kinase (Btk) gene extending 4.2–19 kb beyond the 3′ end of the gene. The DNA immediately downstream of the 3′ end of Btk contains the deafness-dystonia protein gene (DDP). Mutations in this gene have recently been shown to underlie the Mohr–Tranebjaerg syndrome, which is characterized by sensorineural deafness, dystonia, and mental deficiency. Besides the immunodeficiency, our patients exhibited progressive sensorineural deafness. The clue to an associated hearing problem was delayed development of speech in one patient and post-lingual deafness noticed between the age of 3–4 years in the other two. These patients have not yet exhibited significant associated neurologic deficits. [ABSTRACT FROM AUTHOR]

Objective: Autoimmune disease (e.g., Cogan syndrome) and other inflammatory inner ear diseases may ravage the labyrinth if not treated aggressively with antiinflammatory medication. Corticosteroids are the mainstay of treatment, yet, partly because of the existence of the blood-labyrinthine barrier, the ideal drug, dose, and route of administration are currently unknown. Study Design: In the present study, we established cochlear fluid pharmacokinetic profiles of hydro-cortisone, methylprednisolone, and dexamethasone in the guinea pig following oral, intravenous, and topical (intratympanic) administration. High-performance liquid chromatography was used to determine the drug concentrations, and comparisons were made with simultaneous pharmacokinetic profiles from blood and cerebrospinal fluid. Results: Our findings demonstrated a much higher penetration of all three drugs into the cochlear fluids following topical application as compared with systemic administration, with methylprednisolone showing the best profile. Discussion: The results suggested that intratympanic administration of corticosteroids might be more efficacious while avoiding high blood levels and therefore the deleterious side effects of systemic use. Clinical Application: Thirty-seven patients with various inner ear disorders causing sensorineural hearing loss were subsequently treated using intratympanic corticosteroids, 20 with dexamethasone, and 17 with methlyprednisolone. Patients with immune-mediated hearing losses showed the best results, with notable improvement also seen in several cases of a 'sudden deafness.' No benefit was seen in patients with cochlear hydrops or those with sudden deterioration of a preexisting hearing loss. Three patients developed a transient otitis media related to the treatments, easily controlled with antibiotics. There were no cases of treatment-induced hearing loss and no permanent tympanic membrane perforations. Conclusions: Overall, injection of intratympanic corticosteroids for the treatment of hearing loss in inner ear disorders appears to be both safe and highly effective for certain disorders. The concept of this technique is supported by animal experimental data. The findings from the present study warrant further clinical application and experimental investigation. [ABSTRACT FROM AUTHOR]

Objective.—To describe a patient with facial pain, ipsilateral facial dystonia, and phantom supernumerary teeth, beginning after resection of hypertrophic gums. She had familial sensorineural deafness. Background.—Atypical cranial dystonia subsequent to dental procedures is associated with facial pain, dysesthesias, or phantom phenomena, but not with phantom supernumerary teeth. Patients with migraine are susceptible to experience cephalic phantom phenomena after dental procedures. Wynne syndrome is a hereditary autosomal dominant disorder characterized by congenital sensorineural deafness and supernumerary teeth. Methods.—Clinical examination, computerized tomography of paranasal sinuses and facial bones, magnetic resonance imaging of the brain, cranial electrophysiological testing, and electroencephalogram. Results.—A 52-year-old woman with history of migraine without aura for 40 years exhibited focal right facial involuntary tonic contracture accompanying chronic severe pain over the same area after gum resection. She reported a daily sensation of having two extra upper canine teeth pressing on her tongue, simulating vampire's (“Dracula's”) teeth. She had high-frequency bilateral sensorineural deafness. Her computerized tomography studies, brain magnetic resonance imaging, and cranial electrophysiological testing were normal. Conclusion.—This patient with chronic migraine had atypical cranial dystonia beginning after a dental procedure. Her dystonia was complicated by the unusual phenomenon of phantom supernumerary teeth. This condition may be misdiagnosed as atypical or psychogenic facial pain when facial dystonia is localized or subtle and is, therefore, confused with an idiosyncratic gesture or habitual spasm. Her signs and symptoms are reminiscent of Wynne syndrome. [ABSTRACT FROM AUTHOR]

Presents a case report on a girl who was diagnosed with symptoms similar to those of a megalocornea-mental retardation (MMR) syndrome, and a bilateral sensorineural hearing impairment. Background on MMR; Description of the child's physiology; Results of the ophthalmologic examination; Analysis and discussion.

Describes a case of a male child who has an identical syndrome of diaphragmatic hernia, exomphalos, hypertelorism, agenesis of corpus collosum, severe sensorineural deafness and severe myopia. Variety of disorders in the co-occurrence of myopia and hypertelorism; Similarity of the case presented with the autosomal recessive syndrome identified by D. Donnai and M. Barrow in 1993.