Hearing impairment in Stickler syndrome: a systematic review

BACKGROUND: Stickler syndrome is a connective tissue disorder characterized by ocular, skeletal, orofacial and auditory defects. It is caused by mutations in different collagen genes, namely COL2A1, COL11A1 and COL11A2 (autosomal dominant inheritance), and COL9A1 and COL9A2 (autosomal recessive inheritance). The auditory phenotype in Stickler syndrome is inconsistently reported. Therefore we performed a systematic review of the literature to give an up-to-date overview of hearing loss in Stickler syndrome, and correlated it with the genotype. METHODS: English-language literature was reviewed through searches of PubMed and Web of Science, in order to find relevant articles describing auditory features in Stickler patients, along with genotype. Prevalences of hearing loss are calculated and correlated with the different affected genes and type of mutation. RESULTS: 313 patients (102 families) individually described in 46 articles were included. Hearing loss was found in 62.9%, mostly mild to moderate when reported. Hearing impairment was predominantly sensorineural (67.8%). Conductive (14.1%) and mixed (18.1%) hearing loss was primarily found in young patients or patients with a palatal defect. Overall, mutations in COL11A1 (82.5%) and COL11A2 (94.1%) seem to be more frequently associated with hearing impairment than mutations in COL2A1 (52.2%). CONCLUSIONS: Hearing impairment in patients with Stickler syndrome is common. Sensorineural hearing loss predominates, but also conductive hearing loss, especially in children and patients with a palatal defect, may occur. The distinct disease-causing collagen genes are associated with a different prevalence of hearing impairment, but still large phenotypic variation exists. Regular auditory follow-up is strongly advised, particularly because many Stickler patients are visually impaired

Aetiologies after newborn hearing screening

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Ear- and hearing-related impact on quality of life in children with cleft palate : development and pretest of a health-related quality of life (HRQOL) instrument

Objectives: To investigate to what extent middle ear problems and associated hearing loss affect quality of life (QoL) of children born with a cleft palate. Methods: Fifty-five children aged between 6 and 18 years, born with non-syndromic cleft palate +/- cleft lip (CP/L) were included. A new health-related quality of life (HRQOL) questionnaire was generated with consideration of the following domains of QoL: communication, hearing loss, physical symptoms, limitation of activities and socio-emotional impact. Results: Major psychosocial problems were not reported in the majority of children as a result of their ear and hearing problems. However, according to their parents, 2 out of 3 children, had difficulty speaking clearly and understandably. These communication problems led to behavioural problems and social isolation in 1 out of 5 children. Scholastic achievement was negatively influenced by two factors: hearing loss and sleep disturbance due to ear problems. Conclusions: To our knowledge this is the first study to quantitatively measure the ear- and hearing-related impact on QoL in children born with CP/L. Large-scale, multicentre studies are needed to further research and expand on the findings of this pilot study

Association between bone mineral density and hearing loss in osteogenesis imperfecta

Objectives: The main phenotypic characteristic of osteogenesis imperfecta (OI) is bone fragility. In addition, progressive hearing loss develops in about half of the patients apparently independently from the underlying OI genotype. The hearing loss is often associated with abnormal bony changes involving the middle ear ossicles, the stapes footplate and the temporal bone surrounding the otic capsule. We aimed to investigate whether the hearing loss in OI may be related to the overall aberrant bone quality. Methods: Associations between hearing characteristics and bone mineral density were investigated in 56 adults with OI. Following audiological evaluation they were classified as presenting normal hearing (NL H), conductive/mixed hearing loss (C/M HL) or sensorineural hearing loss (SNHL). Areal bone mineral density (aBMD) was measured using lumbar spine (LS) and whole body (WB) dual X-ray absorptiometry (DXA). By means of peripheral computed tomography (pQCT) volumetric BMD (vBMD) was calculated at distal and proximal radius, providing separate results for trabecular and cortical bone. Results: Z-scores demonstrated LS aBMD, WB aBMD and trabecular vBMD to be reduced in OI adults in comparison with the healthy population. Furthermore, patients with C/M HL had lower trabecular BMD compared to those with NL H or SNHL at both whole-group and between-relatives comparisons. Conclusions: It is hypothesized that the OI patients with the lowest trabecular BMD might be more susceptible to accumulating microfractures, which interfere with the bone remodeling inhibition pathways in the temporal bone and, therefore, contribute to stapes footplate fixation and a conductive hearing loss component

Multidisciplinary approach to the child with sex chromosomal mosaicism including a Y-containing cell line

Children born with sex chromosomal mosaicism including material derived from the Y chromosome may present with a broad phenotypical spectrum. Both boys and girls can present with Turner features and functional health problems typically associated with Turner syndrome, but the presence of Y-chromosomal material can modify some aspects of the condition. We retrospectively analyzed the results of our cohort of 21 individuals (14 boys, 7 girls) with sex chromosomal mosaicism including Y-derived material followed at Ghent University Hospital according to our local multidisciplinary Turner surveillance protocol. Results were compared with literature data, focusing on similarities and differences between girls and boys with this condition. Age at diagnosis was lower in boys compared to girls but the difference was not significant. Short stature is a key feature of the condition both in girls and boys, but skeletal maturation may be different between groups. The effects of growth-hormone therapy remain unclear. Cardiac (33%), ear-nose- throat (ENT) (77.8%) and renal (28.6%) problems were as prevalent in boys as in girls from our cohort, and did not differ from literature data. In line with literature reports, a significant difference in the presence of premalignant germ cell tumors between males (0%) and females (42.9%) was found (p = 0.026). Taken together, this study demonstrates the similarities between girls with Turner syndrome and children with sex chromosomal mosaicism including Y-derived material, regardless of the child's gender. Nowadays, girls with Turner syndrome are offered a dedicated multidisciplinary follow-up in many centers. We advocate a similar follow-up program for all children who have sex chromosomal mosaicism that includes Y-derived material, with special attention to growth, cardiac and ear-nose-throat problems, gonadal function and malignancies