Bilateral Cochlear Implants in a Case of Spondyloenchondrodysplasia With Sensorineural Hearing Loss: Case Report

doi:10.21203/rs.3.rs-2003082/v1

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Case Report

Bilateral Cochlear Implants in a Case of Spondyloenchondrodysplasia With Sensorineural Hearing Loss: Case Report

https://doi.org/10.21203/rs.3.rs-2003082/v1

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Background: Spondyloenchondrodysplasia (SPENCD) is a rare autosomal recessive skeletal dysplasia caused by acid phosphates 5 gene mutation. SPENCD has multisystemic manifestations including enchondromas in the long bones or pelvis, skeletal anomalies, immune dysfunctions, and neurological impairments. Out of the wide spectrum of presentation in SPENCD, hearing loss is one of the least presented symptoms.

Case presentation: Here we present a two-year-old female, who visited the otolaryngology clinic concerned about hearing and delayed speech. The patient was started on hearing aids and after investigations, she was diagnosed with SPENCD. After a discussion with the family, the patient underwent a bilateral cochlear implant for sensorineural hearing loss at the age of four, which went uneventfully.

Conclusion: The objective of this report is to highlight the unusual presentation of profound sensorineural hearing loss in a pediatric case with SPENCD that was managed with cochlear implants.

Spondyloenchondrodysplasia

Sensorineural hearing loss

Cochlear implant

Spondyloenchondrodysplasia (SPENCD) is a rare type of skeletal dysplasia caused by mutations in the acid phosphates 5 (ACP5) gene. It is characterized by enchondromas in the long bones or pelvis and skeletal anomalies.^[1] SPENCD has multisystemic clinical manifestations that include immune dysfunctions, and neurological impairments.^[2] It has been commonly reported that SPENCD has signs of an autoimmune disease resembling systemic lupus erythematosus (SLE).^[3] However, in many reported cases the clinical features of SPENCD and the presentation severity vary from one case to another. ^[4] The diagnosis is mainly clinical and is confirmed by genetic analysis.^[2] Out of the wide spectrum of presentation in SPENCD, hearing loss is one of the least presented symptoms. The objective of this report is to highlight the unusual presentation of profound sensorineural hearing loss (SNHL) in a case with SPENCD that was managed with cochlear implants.

A two years old girl, the second child of healthy parents, was delivered via term cesarean section due to decreased oxygen saturation. Was diagnosed later with global developmental delay due to low oxygen during delivery. The mother presented to the otolaryngology clinic by the age of one concerned about hearing and delayed speech. On Ear, Nose, and Throat (ENT) examination: bilateral intact, flat tympanic membranes, the rest of the examination was unremarkable. Further tests like Auditory Brainstem Response (ARB) showed: bilateral profound SNHL and tympanometry showed: type B bilaterally. Computed tomography (CT) scan was done which did not show any abnormalities [Figure 1].

The patient was started on hearing aids and was followed up with speech therapy. Six months later, the patient was evaluated for Cochlear Implant (CI) and was accepted. By the age of two, during the admission for CI insertion, the patient’s regular blood workup showed low hemoglobin therefore the pediatrics team was consulted. Upon investigations, the patient was diagnosed with spondyloenchondrodysplasia with immune dysregulation and monogenic SLE. Therefore she was started on immunosuppressive therapy, Mycophenolate mofetil, hydroxychloroquine, and monthly intravenous immunoglobulin (IVIG), and the CI was recommended to be delayed. The patient continued on immunosuppressive therapy for a year and her hearing was assessed during that time, the family reported no improvement in hearing after the immunosuppressive therapy. Since we were not sure whether the cause of hearing loss in this patient was caused by a cochlear or a central defect, a discussion was done with the pediatrician, the surgeon, and her family for bilateral simultaneous CI. By the age of four, the patient was cleared for surgery and had bilateral CI which went uneventful, the figure below shows a head x-ray postoperative [Figure 2].

Follow-up appointments with the audiology team were arranged, and the patient was comfortable and eager to wear the device daily. In eight months after surgery, the hearing threshold improved by 70 − 80 dB, and the patient showed improvement in speech as well [Figure 3].

SPENCD is an autosomal recessive skeletal dysplasia caused by heterozygous mutations in the ACP5 gene. Mutations in ACP5 will lead to deficiency in tartrate-resistant acid phosphatase (TRAP), an important protein in osteoclasts, macrophages, and dendritic cells, and its primary substrate is osteopontin. The deficiency of TRAP will interfere with the production of type 1 interferon and the dephosphorylation of osteopontin.^[1] If TRAP activity is lost, elevated levels of active phosphorylated osteopontin will lead to skeletal abnormalities and overproduction of interferon type 1. Furthermore, interferon type 1 has a major effect on SLE pathogenesis by promoting the release of nuclear antigens from apoptotic cells and maturation of autoreactive B-cells thereby inducing autoimmunity.^[3]

SPENCD has a wide variety of clinical manifestations; patients can present with neurological, skeletal, or autoimmune manifestations. The neurological manifestations can be developmental delay, ataxia, seizures, or psychosis.^[5] Skeletal manifestations such as skeletal dysplasia, enchondromas of the long bones, and platyspondyly.^[4] As for the autoimmune manifestations, autoimmune thrombocytopenia and systemic lupus erythematosus (SLE) are among the most common ones. A study done by Briggs et al. conducted in 2016, showed that the most common cause of patient referral to a specialized clinic in SPENCD cases before diagnosis was autoimmune or neurological complaints.^[5] SPENCD often coexists with neurological disease and autoimmune dysregulation, which was found in this case. The most autoimmune disease believed to be associated with elevated levels of interferon is SLE, in which it was found that the occurrence of SLE was higher in type 1 interferonopathies.^[4]

A study by Tunkel et al., 2012, was done on 2,365 patients with different skeletal dysplasias to screen for hearing loss and abnormal tympanometry. The study showed that over one-fourth of children and half of adults have hearing loss. Children with skeletal dysplasias have abnormal tympanometry indicating a higher likelihood of middle ear disease and conductive hearing loss.^[6] According to Lyford-Pike, hearing loss in skeletal dysplasia can be conductive, sensorineural, or mixed. A result of a hearing screening program done in 2010 showed that 25% of children with skeletal dysplasia have hearing loss at least in 1 ear, and 50% of them had abnormal tympanometry featuring middle ear dysfunction.^[7] A clinical study on SLE patients showed that the most common otologic symptom is SNHL.^[8] Since the skeletal relation in this patient can be ruled out because the CT scan was normal, we believe the autoimmune aspect had a role in this patient’s hearing loss. Uncontrolled immune system response in autoimmune diseases commonly causes bilateral SNHL.^[9] However, the exact defect, in this case, is still unknown if it is cochlear or central.

To our knowledge, this is the first reported case of SPENCD with SNHL that was managed with cochlear implants and showed clinical improvement.

Acknowledgment: None.

Declaration of Competing Interest: None.

Funding: This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Ethical approval: The study has been approved by our research center and IRB committee at our institution.

Consent: Written informed consent for the publication of this study has been obtained from the patient.

Provenance and peer review: Not commissioned, externally peer-reviewed.

Bilginer, Y., Düzova, A., Topaloğlu, R., Batu, E.D., Boduroğlu, K., Güçer, Ş., et al. (2016). Three cases of spondyloenchondrodysplasia (SPENCD) with systemic lupus erythematosus: a case series and review of the literature. Lupus, [online] 25(7), pp.760–765. doi: 10.1177/0961203316629000. Available at: https://pubmed.ncbi.nlm.nih.gov/26854080/.
Hong, S.W., Huh, K.-H., Lee, J.K. and Kang, J.-H. (2018). Craniofacial anomalies associated with spondyloenchondrodysplasia. Medicine, [online] 97(50). doi: 10.1097/MD.0000000000013644. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6320149/.
Girschick, H., Wolf, C., Morbach, H., Hertzberg, C. and Lee-Kirsch, M.A. (2015). Severe immune dysregulation with neurological impairment and minor bone changes in a child with spondyloenchondrodysplasia due to two novel mutations in the ACP5 gene. Pediatric Rheumatology, 13(1). doi: 10.1186/s12969-015-0035-7. Available at: https://ped-rheum.biomedcentral.com/articles/10.1186/s12969-015-0035-7
Kara, B., Ekinci, Z., Sahin, S., Gungor, M., Gunes, A.S., Ozturk, K., et al. (2020). Monogenic lupus due to spondyloenchondrodysplasia with spastic paraparesis and intracranial calcification: case-based review. Rheumatology International, 40(11), pp.1903–1910. doi: 10.1007/s00296-020-04653-x. Available at: https://link.springer.com/article/10.1007/s00296-020-04653-x
Briggs, T.A., Rice, G.I., Adib, N., Ades, L., Barete, S., Baskar, K., Baudouin, V., Cebeci, A.N., Clapuyt, P., Coman, D., De Somer, L., Finezilber, Y., Frydman, M., Guven, A., Heritier, S., Karall, D., Kulkarni, M.L., Lebon, P., Levitt, D. and Le Merrer, M. (2016). Spondyloenchondrodysplasia Due to Mutations in ACP5: A Comprehensive Survey. Journal of Clinical Immunology, [online] 36, pp.220–234. doi: 10.1007/s10875-016-0252-y. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4792361/.
Tunkel, D., Alade, Y., Kerbavaz, R., Smith, B., Rose-Hardison, D. and Hoover-Fong, J. (2012). Hearing loss in skeletal dysplasia patients. American Journal of Medical Genetics. Part A, [online] 158A(7), pp.1551–1555. doi: 10.1002/ajmg.a.35373. Available at: https://pubmed.ncbi.nlm.nih.gov/22628261/
Lyford-Pike, S., Hoover-Fong, J. and Tunkel, D.E. (2012). Otolaryngologic Manifestations of Skeletal Dysplasias in Children. Otolaryngologic Clinics of North America, 45(3), pp.579–598. doi: 10.1016/j.otc.2012.03.002. Available at: https://pubmed.ncbi.nlm.nih.gov/22588038/
Di Stadio, A. and Ralli, M. (2017). Systemic Lupus Erythematosus and hearing disorders: Literature review and meta-analysis of clinical and temporal bone findings. The Journal of International Medical Research, [online] 45(5), pp.1470–1480. doi: 10.1177/0300060516688600. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5718712/#:~:text=The%20most%20common%20otologic%20symptom.
Ciorba, A., Corazzi, V., Bianchini, C., Aimoni, C., Pelucchi, S., Skarżyński, P.H. and Hatzopoulos, S. (2018). Autoimmune inner ear disease (AIED): A diagnostic challenge. International Journal of Immunopathology and Pharmacology, 32, p.205873841880868.

No competing interests reported.

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Bilateral Cochlear Implants in a Case of Spondyloenchondrodysplasia With Sensorineural Hearing Loss: Case Report

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