A novel heterozygous variant of the SALL1 gene with atypical Townes-Brocks syndrome phenotypes in Chinese family.

Townes-Brocks syndrome (TBS) is an autosomal dominant disorder characterised by the triad of anorectal, thumb, and ear malformations. It may also be accompanied by defects in kidney, heart, eyes, hearing, and feet. TBS has been demonstrated to result from heterozygous variants in the SALL1 gene, which encodes zinc finger protein believed to function as a transcriptional repressor. The clinical characteristics of an atypical TBS phenotype patient from a Chinese family are described, with predominant manifestations including external ear dysplasia, unilateral renal hypoplasia with mild renal dysfunction, and hearing impairment. A novel heterozygous variant c.3060T>A (p.Tyr1020*) in exon 2 of the SALL1 gene was identified in this proband. Pyrosequencing of the complementary DNA of the proband revealed that the variant transcript accounted for 48% of the total transcripts in peripheral leukocytes, indicating that this variant transcript has not undergone nonsense-mediated mRNA decay. This variant c.3060T > A is located at the terminal end of exon 2, proximal to the 3' end of the SALL1 gene, and exerts a relatively minor impact on protein function. We suggest that the atypical TBS phenotype observed in the proband may be attributed to the truncated protein retaining partial SALL1 function.

Correlations Between Auricular Tenderness and Symptoms in Korean Adults.

The purpose of this study was to examine the correlation between auricular tenderness and subjective symptoms. A descriptive correlational study design was followed, which was also the second analysis of a randomized controlled trial. This study was performed in the Republic of Korea from September 2013 to February 2017. The Patient Health Questionnaire-9, the Constipation Assessment Scale, and the Nicotine Dependence Syndrome Scale were used. One hundred thirty-three participants displayed ear tenderness, whereas 84 participants did not. Adults with auricular tenderness reported more symptoms, such as sputum, rhinitis, constipation, stress, mood swings, and depressive symptoms compared with adults without (with tenderness: 4.14 ± 2.94, without tenderness: 2.92 ± 2.45; t = 3.32, P = .001). Finally, auricular acupressure points were positively correlated with various symptoms such as sputum, constipation, nicotine addiction, stress, cough, and rhinitis. Auricular palpation could be used to detect a disease at an early stage.

Hearing stimulation of the pediatric patient with congenital aural atresia: surgical and audiological evaluation of 38 patients.

The aim of this work is to stress the importance of and discuss the timing and options for the treatment of congenital aural atresia (CAA), including non-surgical alternative treatment modalities and amplification, and to report the audiological and surgical results of a series of patients. Thirty-eight children with CAA were evaluated with regard to hearing and anatomical anomalies accompanying CAA: the state of the ossicles and the facial nerve, postoperative complications and audiological results. The ages of the patients ranged between 4 and 18 years, with a mean of 10 years. All underwent surgical treatment; 32 had unilateral atresia, while 6 had bilateral atresia. The mean follow-up duration was 7 months. The facial canal was dehiscent in 36.8% of cases. In 70.2% cases, the malleus and incus were present as an ossicular mass, fixed and attached to the atretic bone. The stapes was normal in 97.3% of the patients; in 2.7% the suprastructure was deformed. The success rate, defined as an air-bone gap of 20 dB or less, was 63.1% in this series of patients. If atresia is bilateral, very early hearing stimulation to prevent the maldevelopment of children's speech and cognitive skills is of the utmost importance. In unilateral cases, surgery may be postponed until early adulthood, when the patient is able to make his/her own decision and cooperate in the treatment and postoperative aspects.

Blood flow dynamics in reconstructed auricles.

Ear reconstruction with autologous rib cartilage is performed in stages. Restitution of blood flow between the separate stages is crucial to obtain a good result. Laser Doppler perfusion imaging (LDPI) and local temperature were measured in reconstructed and normal ears in response to indirect heating. Ten persons who had had a unilateral ear reconstruction were included in the study. At a minimum, 157 days had passed since the last operation. LDPI showed no difference in blood flow between the reconstructed ear and the normal ear, neither before nor after indirect heating. The upper part of the normal ear was slightly cooler than the corresponding part in the reconstructed ear. Indirect heating caused an increase of LDPI-values and temperatures in the upper, middle, and lower part of the ear both in the reconstructed ear and the normal one. Skin blood flow recovers after 3-stage ear reconstruction and shows normal dynamic response upon indirect heating.

Association of microtia with maternal nutrition.

BACKGROUND: Few studies have investigated the potential association of maternal dietary intake and risk of microtia among offspring. METHODS: The study included deliveries from 1997 to 2005 from the National Birth Defects Prevention Study. Nonsyndromic cases of microtia were compared to nonmalformed, population-based, live-born control infants by estimating adjusted odds ratios (ORs) and 95% confidence intervals (CIs) from logistic regression models that included maternal race or ethnicity, education, folic acid-containing supplement intake, fertility treatment, study site, and total energy intake. RESULTS: Comparing intake in the lowest 10th percentile versus the 10th to 90th percentiles, lower maternal intakes of carbohydrate (OR, 1.59; 95% CI, 1.07-2.38) and dietary folate (OR, 1.57; 95% CI, 1.09-2.25) were associated with elevated risk of microtia. In addition, results suggested that higher diet quality (as measured by the Diet Quality Index, and comparing the highest with the lowest quartile) was protective, but the CI did not exclude one (OR, 0.73; 95% CI, 0.50-1.07). Results were similar among obese and nonobese women. CONCLUSIONS: These data contribute to the limited body of evidence regarding the potential contribution of maternal nutrition to the etiology of microtia.

Potential reproductive toxicity of Largehead Atractylodes Rhizome, the most commonly used Chinese medicine for threatened miscarriage.

BACKGROUND: Largehead Atractylodes Rhizome (LAR) is the most commonly used Chinese medicine to prevent early pregnancy loss due to threatened miscarriage. However, its safety profile during pregnancy is still not available. Here we aimed to identify the potential adverse effects of LAR on embryo-fetal development as well as prenatal and post-natal growth. METHODS: Pregnant mice, rats and rabbits were orally administered with LAR extracts in various doses (from 1×, 2×, 3× and up to 6× clinical doses) at different gestational periods (implantation, gastrulation, organogenesis, maturation and whole gestation). Maternal effects on weight loss, implantation failure and fetal resorption and perinatal effects on developmental delay, growth restriction and congenital malformations were studied. RESULTS: In mice, with early LAR exposure, a significant decrease in fetal growth parameters and a significant increase in post-implantation loss were identified. With late LAR exposure, significant increases in gestational duration as well as prenatal and post-natal mortality were found. At high clinical doses, congenital skeletal malformations were recorded. In rabbits, fetal resorption, hydrops fetalis and short ear anomaly were observed. No significant adverse effects were found in rats. CONCLUSIONS: Potential reproductive toxicity of LAR in pregnant animals was identified within the clinical dose. Caution should be taken in clinical applications of LAR during pregnancy.

Association of microtia with maternal obesity and periconceptional folic acid use.

The study objective was to examine the association of microtia with maternal intake of folic-acid-containing supplements and obesity. The study data included deliveries from 1997 to 2005 from the National Birth Defects Prevention Study. Non-syndromic cases of microtia were compared to non-malformed, population-based liveborn control infants, by estimating adjusted odds ratios (AORs) and 95% confidence intervals (CIs) from logistic regression models that included maternal race/ethnicity, education, and study site. Maternal obesity was only weakly associated with microtia. Maternal periconceptional intake of folic-acid-containing vitamin supplements reduced the risk for microtia, but only among non-obese women (OR: 0.63; 95% CI: 0.44-0.91). The reduced risk was stronger when analyses were restricted to isolated cases (OR: 0.51; 95% CI: 0.34-0.77), and it was independent of the level of maternal dietary folate intake. Adjusting for maternal race/ethnicity did not reveal alternative interpretations of this association. This analysis suggests that maternal periconceptional intake of folic-acid-containing supplements may provide protection from microtia for non-obese women.

Auricular hematoma and cauliflower deformation of the ear: from art to medicine.

Auricular hematoma and cauliflower deformation of the ear are unique in several respects. Knowledge about it began, in antiquity, through artists, particularly Greek and Roman, and then Japanese in the 18th century with their representation of cauliflower deformation of the ear on sculptures and paintings of pugilists and wrestlers. It is only in the 19th century that physicians began to make substantive progress in understanding this abnormality. It was first thought to be associated with mental disease, but by the beginning of the 20th century, its etiology was recognized as being caused by trauma and was then named auricular hematoma. The second step in the understanding of this affliction was the observation that auricular hematoma progresses toward cauliflower deformation of the ear, which was named cauliflower ear. Recognition of this evolution led to the development of therapies. During the second half of the 20th century, different treatments were developed. They included various hematoma drainage techniques with special bandages to prevent hematoma recurrence and ensuing progression to cauliflower ear. In summary, cauliflower deformation of the ear is an old artistic affliction that has only recently received medical attention.

Binaural hearing, atresia, and the masking dilemma.

A masking dilemma occurs when energy from a non-test ear crosses over the head to a test ear. In cases of bilateral atresia, obtaining thresholds on the poorer ear is problematic. Near threshold, however, sufficient ear-bone isolation exists to test with validity but not so much above threshold, even for the ultra-high (> 10 kHz) frequencies. This aspect of the bone audiogram should not be overlooked. We suggest two uses of binaural bone conduction hearing to help resolve the dilemma--one an auditory brainstem response variation, the other a high-frequency lateralization procedure. Both are also applicable in unilateral atresia with and without a sensorineural component. The use of an insert earphone for masking in the unobstructed ear will provide adequate interaural attenuation to resolve most but not all dilemmas. That is to say, the maximum isolation of an insert earplug is on the order of 100 dB, so it has a limit. The dilemma extends through the ultra-high frequencies (> 10 kHz) because the intra-aural attenuation is no more than 10 dB. In the cited case of unilateral congenital atresia of the external ear, the intra-aural threshold differences in the high frequencies plus the resolution of the masking dilemma in the low frequencies (without the need for more masking) leads us to conclude that the unmasked thresholds are valid. Masking can be extended above 10 kHz, but this is not generally within the capacity of commercial audiometers, a feature that should be included.

Time-intensity trading in bilateral congenital aural atresia patients.

In an effort to examine the rules by which information of bilaterally applied bone-conducted signals arising from interaural time differences (ITD) and interaural intensity differences (IID) is combined, data were measured for continuous 500 Hz narrow band noise at 65-70 dB HL in 11 patients with bilateral congenital aural atresia. Time-intensity trading functions were obtained by shifting the sound image towards one side using ITD, and shifting back to a centered sound image by varying the IID in the same ear (auditory midline task). ITD values were varied from -600 to +600 micros at 200 micros steps, where negative values indicate delays to the right ear. The results indicate that time-intensity trading is present in patients with bilateral aural atresia. The gross response properties of time-intensity trading in response to bone-conducted signals were comparable in patients with bilateral aural atresia and normal-hearing subjects, though there was a larger inter-subject variability and higher discrimination thresholds across IIDs in the atresia group. These results suggest that the mature auditory brainstem has a potential to employ binaural cues later in life, although to a restricted degree. A binaural fitting of a bone-conducted hearing aid might optimize binaural hearing and improve sound lateralization, and we recommend now systematically bilateral fitting in aural atresia patients.

Magnesium deficiency as a cause of hypocalcemia in the CHARGE association.

OBJECTIVE: To discover the mechanism of hypocalcemia in a patient with the CHARGE (coloboma, heart disease, atresia choanae, retarded growth and development, genital hypoplasia, and ear anomalies) association. RESEARCH DESIGN: Chemical and metabolic studies of serum, urine, stool, and muscle specimens. SETTING: A university hospital affiliated with a municipal hospital. PARTICIPANT: One patient with the CHARGE association and refractory hypocalcemia. MEASUREMENTS AND RESULTS: Serum calcium level was 0.91 mmol/L (reference range, 2.20 to 2.58 mmol/L) and serum magnesium level was 0.34 mmol/L (reference range, 0.80 to 1.20 mmol/L) prior to any therapy. After parenteral calcium and magnesium therapy, hypocalcemia persisted (1.46 mmol/L), while the serum magnesium level was 0.84 mmol/L. A needle biopsy of skeletal muscle tissue for the magnesium content confirmed a total magnesium deficiency despite normomagnesemia (muscle magnesium content, 517 micrograms/g [reference range, 800 to 1100 micrograms/g]). Magnesium deficiency was secondary to secretion of magnesium into the gastrointestinal tract (with a daily magnesium intake of 190 mg, a 24-hour nondiarrheal fecal excretion of magnesium was 2019 mg/kg [reference range, < 1000 mg/kg of stool weight]). INTERVENTIONS: Hypocalcemia was corrected only after 7 weeks of continual parenteral magnesium supplements to replenish the tissue magnesium deficiency. CONCLUSIONS: Patients with the CHARGE association often have hypocalcemia. Magnesium deficiency (with or without hypomagnesemia) is a cause of the hypocalcemia in at least one patient and may prove of significance in others.