Choanal atresia is an uncommon condition with an incidence of 1:5,000-8,000 live births, affecting females more frequently and often associated with other malformations. This case report presents a 42-year-old female patient who was born with bilateral choanal atresia and intervened surgically for the first time at birth. However, the formed orifice was reobstructed a few months afterward, necessitating reoperation in adulthood. The purpose of this case report is to describe bilateral choanal atresia in detail, including its clinical presentation, epidemiology, diagnosis, pathogenesis, and therapeutic approach. It aims to enhance understanding of this rare but significant condition.

BACKGROUND: The present study aimed to test the hypothesis stating that the cognitive potential of individuals with deafblindness is equal to those without a deafblind condition, an assumption that until now has been empirically unsubstantiated within the field of deafblindness.
METHODS: To explore the assumption, 15 children and adolescents with CHARGE underwent cognitive assessment with WISC-V using a sequential two-level assessment design. The 1st level involved standardized test conditions. The 2nd level was designed as a continuation of the performances obtained from the 1st level and involved accommodations to compensate for sensory motor impairment. Statistical procedures involved the sample as a whole and when divided into two subgroups: (i) participants with CHARGE without deafblindness; (ii) participants with CHARGE and deafblindness using the 1st level scores as base line.
RESULTS: Although results showed significantly lower scores in the deafblind subgroup with standardized procedures, they approximated the others after accommodating for their sensory deficits. This positive increase proved significant.
CONCLUSIONS: Findings supported the assumption of equal cognitive potential of individuals with and without deafblindness. Results indicated that the children and adolescents with deafblindness had most effect of the accommodations, enabling them to approximate the results of the subgroup without deafblindness. These gains were attributed enhanced accessibility endorsed by the accommodations and represented the participants latent cognitive dispositions only realized under certain circumstances.

CHARGE syndrome, characterized by a distinct set of clinical features, has been linked primarily to mutations in the CHD7 gene. Initially defined by specific clinical criteria, including coloboma, heart defects, choanal atresia, delayed growth, and ear anomalies, CHARGE syndrome\'s diagnostic spectrum has broadened since the identification of CHD7. Variants in this gene exhibit considerable phenotypic variability, leading to the adoption of the term \"CHD7 disorder\" to encompass a wider range of associated symptoms. Recent research has identified CHD7 variants in individuals with isolated features such as autism spectrum disorder or gonadotropin-releasing hormone deficiency. In this study, we present three cases from two different families exhibiting audiovestibular impairment as the primary manifestation of a CHD7 variant. We discuss the expanding phenotypic variability observed in CHD7-related disorders, highlighting the importance of considering CHD7 in nonsyndromic hearing loss cases, especially when accompanied by inner ear malformations on MRI. Additionally, we underscore the necessity of genetic counseling and comprehensive clinical evaluation for individuals with CHD7 variants to ensure appropriate management of associated health concerns.

UNASSIGNED: CHARGE syndrome is a rare disorder that causes congenital abnormalities in multiple organs, including secondary hypogonadism. We report, herein, a unique case of CHARGE syndrome with both primary and secondary hypogonadism and discuss the possible causes and pathogenesis in this patient.
UNASSIGNED: A 15-year-old boy with delayed secondary sexual characteristics and non-palpable testes was referred to our hospital. Physical examination and detection of a chromodomain-helicase-deoxyribonucleic acid-binding protein 7 gene mutation confirmed CHARGE syndrome. Hormone stimulation tests suggested both primary and secondary hypogonadism. Laparoscopic bilateral orchiectomy was performed because of decreased testosterone production and atrophy in both testes. Pathological examination of the testes revealed maturation arrest, germ cell neoplasm in situ, and decreased expression of steroid synthase.
UNASSIGNED: This appears to be the first report of CHARGE syndrome with both primary and secondary hypogonadism demonstrated in endocrinological and histological examinations.

UNASSIGNED: In resource-limited settings, patients with uncommon phenotypes often face prolonged diagnostic journeys and potential misdiagnoses. Coloboma, heart defects, atresia choanae, restricted growth and development, genital and ear abnormalities syndrome (CHARGE) syndrome, a congenital condition affecting various body parts such as the heart, ears, eyes, and genitals, exemplifies this challenge.
UNASSIGNED: We present the case of a 21-year-old male patient from Ecuador who exhibited hypogonadism, facial deformities, and stunted growth. Due to the scarcity of genetic specialists and limited access to genetic testing in Ecuador, the patient received a misdiagnosis of Noonan syndrome. However, a correct diagnosis of CHARGE syndrome was ultimately reached after eight years, facilitated by genetic sequencing that identified a novel mutation in the Chromodomain helicase DNA binding protein 7 gene.
UNASSIGNED: This case highlights the critical role of meticulously assessing patients\' symptoms and emphasizes the necessity for enhanced collaboration among physicians and researchers. Such efforts are pivotal in advancing healthcare access and equity for individuals in developing nations.

UNASSIGNED: CHARGE syndrome is a rare genetic disorder characterized by several distinct features. The presence of fetal ear abnormalities could be the early indicator of CHARGE syndrome. Subsequent prenatal diagnosis is essential to confirm the disorder. This is significant because the patient may receive genetic counseling and appropriate disposal based on the accurate diagnosis.
UNASSIGNED: CHARGE syndrome is a rare genetic disorder with multiple specific clinical features. The prenatal diagnosis is crucial but rarely achieved. We report a fetus with fetal external ear abnormality detected by ultrasound at 22nd week of gestation. Postnatal examination revealed an external ear abnormality, a mild atrial septal defect, and other clinical signs of CHARGE syndrome. A de novo pathogenic nonsense mutation in the CHD7 gene (c.406C > T, p.Q136X in exon 2) was identified to cause the disorder. Our study demonstrated that prenatal diagnosis and genetic testing were recommended to obtain a solid diagnosis of CHARGE syndrome when fetal external ear abnormality was detected by ultrasound examination.

Mutations in the Chromodomain helicase DNA-binding protein 7 - coding gene (CHD7) cause CHARGE syndrome (CS). Although craniofacial and skeletal abnormalities are major features of CS patients, the role of CHD7 in bone and cartilage development remain largely unexplored. Here, using a zebrafish (Danio rerio) CS model, we show that chd7-/- larvae display abnormal craniofacial cartilage development and spinal deformities. The craniofacial and spine defects are accompanied by a marked reduction of bone mineralization. At the molecular level, we show that these phenotypes are associated with significant reduction in the expression levels of osteoblast differentiation markers. Additionally, we detected a marked depletion of collagen 2α1 in the cartilage of craniofacial regions and vertebrae, along with significantly reduced number of chondrocytes. Chondrogenesis defects are at least in part due to downregulation of htr2b, which we found to be also dysregulated in human cells derived from an individual with CHD7 mutation-positive CS. Overall, this study thus unveils an essential role for CHD7 in cartilage and bone development, with potential clinical relevance for the craniofacial defects associated with CS.
Patients with CHARGE syndrome exhibit skeletal defects. CHARGE syndrome is primarily caused by mutations in the chromatin remodeler-coding gene CHD7. To investigate the poorly characterized role of CHD7 in cartilage and bone development, here, we examine the craniofacial and bone anomalies in a zebrafish chd7-/- mutant model. We find that zebrafish mutant larvae exhibit striking dysmorphism of craniofacial structures and spinal deformities. Notably, we find a significant reduction in osteoblast, chondrocyte, and collagen matrix markers. This work provides important insights to improve our understanding of the role of chd7 in skeletal development.

Inner ear morphogenesis requires tightly regulated epigenetic and transcriptional control of gene expression. CHD7, an ATP-dependent chromodomain helicase DNA-binding protein, and SOX2, an SRY-related HMG box pioneer transcription factor, are known to contribute to vestibular and auditory system development, but their genetic interactions in the ear have not been explored. Here, we analyzed inner ear development and the transcriptional regulatory landscapes in mice with variable dosages of Chd7 and/or Sox2. We show that combined haploinsufficiency for Chd7 and Sox2 results in reduced otic cell proliferation, severe malformations of semicircular canals, and shortened cochleae with ectopic hair cells. Examination of mice with conditional, inducible Chd7 loss by Sox2CreER reveals a critical period (~E9.5) of susceptibility in the inner ear to combined Chd7 and Sox2 loss. Data from genome-wide RNA-sequencing and CUT&Tag studies in the otocyst show that CHD7 regulates Sox2 expression and acts early in a gene regulatory network to control expression of key otic patterning genes, including Pax2 and Otx2. CHD7 and SOX2 directly bind independently and cooperatively at transcription start sites and enhancers to regulate otic progenitor cell gene expression. Together, our findings reveal essential roles for Chd7 and Sox2 in early inner ear development and may be applicable for syndromic and other forms of hearing or balance disorders.

Choanal atresia occurs in about 1 in 5000 births and is associated with other structural and genetic abnormalities. Choanal atresia is usually diagnosed postnatally due to respiratory distress, and rarely diagnosed antenatally. Here, a woman with severe polyhydramnios is described, whose fetus was diagnosed antenatally with isolated bilateral choanal atresia, as evident by persistent absence of flow through the nostrils on ultrasound. A literature review is presented of the antenatal findings of choanal atresia, using ultrasound and other imaging modalities. An association of choanal atresia with polyhydramnios should be considered. Examining flow through the fetal nose, using color Doppler, might aid in diagnosing choanal atresia. If this condition is suspected, a detailed ultrasound scan should be done to rule out other anomalies. Fetal magnetic resonance imaging has been suggested as an additional imaging tool in selected patients. Genetic counselling and invasive prenatal testing should be offered.

Individuals with Kabuki syndrome type 1 (KS1) often have hearing loss recognized in middle childhood. Current clinical dogma suggests that this phenotype is caused by frequent infections due to the immune deficiency in KS1 and/or secondary to structural abnormalities of the ear. To clarify some aspects of hearing loss, we collected information on hearing status from 21 individuals with KS1 and found that individuals have both sensorineural and conductive hearing loss, with the average age of presentation being 7 years. Our data suggest that while ear infections and structural abnormalities contribute to the observed hearing loss, these factors do not explain all loss. Using a KS1 mouse model, we found hearing abnormalities from hearing onset, as indicated by auditory brainstem response measurements. In contrast to mouse and human data for CHARGE syndrome, a disorder possessing overlapping clinical features with KS and a well-known cause of hearing loss and structural inner ear abnormalities, there are no apparent structural abnormalities of the cochlea in KS1 mice. The KS1 mice also display diminished distortion product otoacoustic emission levels, which suggests outer hair cell dysfunction. Combining these findings, our data suggests that KMT2D dysfunction causes sensorineural hearing loss compounded with external factors, such as infection.