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 Table of Contents  
CASE REPORT
Year : 2022  |  Volume : 28  |  Issue : 1  |  Page : 62-64

Auditory neuropathy spectrum disorder in two siblings with congenital cytomegalovirus infections: Two rare cases


Department of Ear Nose Throat-Head and Neck Surgery, Faculty of Medicine, Universitas Indonesia/Dr. Cipto Mangunkusumo National Hospital, Jakarta, Indonesia

Date of Submission03-Feb-2021
Date of Acceptance01-Mar-2021
Date of Web Publication25-Apr-2022

Correspondence Address:
Dr. Ronny Suwento
Department of Ear Nose Throat-Head and Neck Surgery, Faculty of Medicine, Universitas Indonesia/Dr. Cipto Mangunkusumo National Hospital, Jakarta
Indonesia
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/indianjotol.indianjotol_25_21

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  Abstract 


Auditory neuropathy spectrum disorder (ANSD) is a rare hearing disorder when signal transmission is disrupted on the auditory pathway. Infection is one of the multifactorial causes of ANSD. Only a few researchers have reported the cases of ANSD caused by congenital cytomegalovirus (CMV) infection, and fewer have presented cases involving siblings. In our study, the two patients were siblings, aged 3 years and 7 months and 8 months. They were born prematurely, had microcephaly; anti-CMV IgG levels were reactive. Distortion product otoacoustic emissions test was normal. A click auditory brainstem response showed that no wave was detected with an 80 dB stimulus, and a cochlear microphonic response was obtained. No abnormality in the middle ear was observed, and negative acoustic reflexes were noted. Hearing habilitation with a low-gain hearing aid, speech therapy, and motoric habilitation was planned, and the patients were referred to the pediatric neurology for CMV management.

Keywords: Auditory neuropathy, congenital cytomegalovirus, hearing loss


How to cite this article:
Suwento R, Hajarani K, Zizlavsky S, Airlangga TJ. Auditory neuropathy spectrum disorder in two siblings with congenital cytomegalovirus infections: Two rare cases. Indian J Otol 2022;28:62-4

How to cite this URL:
Suwento R, Hajarani K, Zizlavsky S, Airlangga TJ. Auditory neuropathy spectrum disorder in two siblings with congenital cytomegalovirus infections: Two rare cases. Indian J Otol [serial online] 2022 [cited 2022 Nov 29];28:62-4. Available from: https://www.indianjotol.org/text.asp?2022/28/1/62/343763




  Introduction Top


The term auditory neuropathy (AN), nowadays better known as AN spectrum disorders (ANSD) was first introduced by Arnold Starr in 1996.[1],[2],[3] It is characterized by normal function of cochlear outer hair cells, absent auditory brainstem response (ABR) waveform, and the presence of cochlear microphonic wave.[1],[2] The prevalence of ANSD is 8.44% in children with severe hearing loss.[4] ANSD is a challenging condition since its risk factors, causes, and pathogenesis are still unclear. This case report aims to improve clinicians' understanding the risk factors of ANSD, including congenital cytomegalovirus (CMV) infection, so that early diagnosis and appropriate treatment can be provided.


  Case Report Top


First case

A 3 years and 7-month-old boy came to Ear, Nose, and Throat (ENT) outpatient clinic due to delayed speech and motoric development. The patient occasionally responded when he was called or heard a loud noise. The patient was diagnosed with congenital CMV infection and received valganciclovir for 18 months, but the medication was discontinued at the age of 2 years and 2 months.

The patient is the first child of two siblings, born spontaneously at 32 weeks gestational age, with a birth weight of 2,300 g and no risk factors toward congenital hearing loss. The patient experienced recurrent febrile seizures at the age of 8 months. During pregnancy, the mother never experienced a fever and did not undergo a TORCH examination. The patient had microcephaly and spastic extremities and had not been able to sit and stand. A tympanometry test showed a normal middle ear and negative acoustic reflexes on both ears, and behavioral audiometry results showed mild to moderate hearing loss (40–50 dB). The distortion product otoacoustic emissions (DPOAE) results showed normal function on both cochleae. A click ABR test showed that the ABR waveform was absent with 80 dB of stimulus, and a cochlear microphonic response was obtained in both ears [Figure 1]. The auditory steady state response (ASSR) results indicated bilateral moderate hearing loss. A serological TORCH (toxoplasma rubella CMV herpes) test showed that anti-CMV immunoglobulin G (IgG) = 2,241.6 (reactive) and nonreactive CMV IgM levels at 1 year and 8 months of age and that anti-CMV IgG = 753.8 (reactive) and anti-CMV IgM = 0.4 (nonreactive) at 3 years and 7 months of age. Based on the clinical symptoms and laboratory and audiological tests, the diagnosis was bilateral moderate ANSD, congenital CMV, delayed speech, and cerebral palsy.
Figure 1: Results of the first patient's click auditory brainstem response examination. First picture is for left ear and the second picture is for the right ear. Cochlear microphonic response on both ears was showed in the red circle

Click here to view


Second case

An 8-month-old boy (the younger sibling of the first patient) did not respond when called or only responded to loud sounds such as car horns. The patient was referred from the pediatric department for hearing evaluation with a diagnosis of congenital CMV infection, epilepsy, and cerebral palsy. The patient was born spontaneously at 36 weeks of gestation, with a birth weight of 2500 g; he did not have risk factors toward hearing loss. The patient had delayed motoric development. He could lift his head by the age of 7 months old. From the age of 3 months, he often experienced seizures lasting for 3 to 5 s without fever. Our patient had microcephaly and hypotonic extremities. A tympanometry test showed a normal middle ear with negative acoustic reflexes in both ears. The results of behavioral audiometry were bilateral moderate hearing loss. A click ABR test did not detect a waveform with 80 dB stimulus, but cochlear microphonic waves appeared in both ears. The ASSR test corresponded to severe hearing loss in both ears. A hearing evaluation was done 6 months later (at 1 year and 4 months of age); the results of the behavioral audiometry were bilateral mild-to-moderate hearing loss, while the result of DPOAE showed normal cochlear function on both ears. A click ABR showed no waves detected with an 80 dB stimulus in the left ear and up to a 90 dB stimulus in the right ear. Cochlear microphonic waves appeared in both ears [Figure 2]. The ASSR results were in accordance with bilateral mild sensorineural hearing loss. A TORCH laboratory test at 8 months old found that anti-CMV IgG = 128 (reactive) and anti-CMV IgM = 0.5 (nonreactive). Based on clinical symptoms and laboratory and audiological tests, the diagnosis for the second case was bilateral mild ANSD, congenital CMV infection, epilepsy, and cerebral palsy.
Figure 2: Results of the second patient's click auditory brainstem response examination. First picture is for left ear and the second picture is for the right ear. Cochlear microphonic response on both ears was showed in the red circle

Click here to view


Furthermore, low-gain hearing aid fittings were planned in both cases. The management of speech and delayed motoric development and treatments for the CMV infections and the neurological disorders will be done in an integrated manner with relevant medical professionals.


  Discussion Top


Two cases of bilateral ANSD were reported in two boys aged 3 years and 7 months and 8 months. The siblings also suffered from congenital CMV infections and cerebral palsy. In both cases, normal OAE results, altered or absent click ABR waves, and cochlear microphonic responses (a valid measure of hair cell function) met the minimum criteria for a diagnosis of ANSD.[1],[2] Acoustic reflex examinations, with negative results confirmed in both cases, also supported the ANSD diagnoses.

Moser-Starr et al. stated that as many as 50% of ANSD patients do not have a clear etiology.[5] Some researchers have suggested that ANSD can be caused by an infection. However, they do not explicitly state the type of infection.[6] In these cases, ANSD is likely to be caused by congenital CMV infections. The definitive diagnosis of congenital CMV is based on CMV immunoglobulin tests. Unfortunately, in both cases, TORCH laboratory tests were not performed within 3 weeks after birth. Serological test results were attained at the age of 1 year and 8 months in the first patient and at 8 months in the second patient. Both showed reactive anti-CMV IgG and nonreactive anti-CMV IgM levels. Congenital CMV infection as a possible cause could not be detected early since no serologic CMV tests were performed during pregnancy. Moreover, CMV infection does not cause clear clinical symptoms during pregnancy. Gantt also explained that the diagnosis of congenital CMV is often missed in asymptomatic infants due to a late serologic test, as happened in both cases.[7] The diagnosis of congenital CMV in both cases is confirmed based on clinical symptoms, namely developmental disorders, neurological deficits, and hearing loss.

ANSD cases caused by congenital CMV infections are rare. A study conducted by Foulon et al. in infants with congenital CMV infections showed that 18 infants had abnormal ABR and OAE results and cochlear microphonic waves were found, so they did not match the ANSD picture.[8] Based on literature searches, only two authors have reported cases of ANSD with CMV infection. In the first study, Baerts et al. reported one case of ANSD in a premature infant that occurred at the time of a post-atal infection.[9] The results of a urine culture test at birth were negative, but the results of a breast milk examination were positive in the 6th week. In the second study, Natale et al. conducted a retrospective study of 60 infants with congenital CMV infections and found that the incidence of ANSD was 16/60 (26.67%).[10] In these 60 infants, no symptomatic abnormalities were found (isolated ANSD) other than hearing loss with OAE depictions accompanied by V waves in abnormal click ABR tests. Natale et al. explained that delays in auditory pathway maturation might affect the hearing of infants with ANSD.[10]

The first step in the management of ANSD is educating parents about the patient's current condition and changes in clinical symptoms that may occur as well as treatment and motor and hearing habilitation options. Both cases were planned for fitting low-gain hearing aids. The management of developmental problems, delayed speech, and the treatment of CMV infections and neurological disorders will be approached in an integrated manner with relevant medical professionals. Unfortunately, the patients have not returned for the hearing aid program since the patients resides in another province and are constrained by the COVID-19 pandemic situation.

The strength of this case report is that the ANSD diagnoses were made according to the minimum criteria along with additional criteria. Meanwhile, the limitations in both cases were the late diagnoses of congenital CMV and the lack of new-born hearing screenings in both cases.

ANSD in siblings is rare, as the cause appears to be a congenital CMV infection, which has never been reported in a scientific journal. Although it is rare, congenital CMV infection needs to be considered a risk factor for ANSD.

To insure early ANSD detection, new-born hearing screenings with OAEs followed by automated ABRs are strongly recommended for all new-borns in well-baby nurseries and NICU settings. Since CMV infections can be transmitted transplacentally, it is necessary to carry out routine TORCH serologic tests in pregnant women. Genetic evaluations are also recommended.

Acknowledgment

We are thanking Indonesian Medical Education and Research Institute writing assistant for assisting us in writing this case report.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

Informed Consent

General consent was obtained in which patients agree in the research use of clinical records and data with anonymization



 
  References Top

1.
Starr A, Rance G. Auditory neuropathy. Handb Clin Neurol 2015;129:495-508.  Back to cited text no. 1
    
2.
Roush P, Frymark T, Venediktov R, Wang B. Audiologic management of auditory neuropathy spectrum disorder in children: A systematic review of the literature. Am J Audiol 2011;20:159-70.  Back to cited text no. 2
    
3.
Roush PA. Children with auditory neuropathy spectrum disorder. In: Seewald R, Tharpe AM, editors. Comprehensive Handbook of Pediatric Audiology. San Diego: Plural Publishing; 2011. p. 734-50.  Back to cited text no. 3
    
4.
Foerst A, Beutner D, Lang-Roth R, Huttenbrink KB, von Wedel H, Walger M. Prevalence of auditory neuropathy/synaptopathy in a population of children with profound hearing loss. Int J Pediatr Otorhinolaryngol 2006;70:1415-22.  Back to cited text no. 4
    
5.
Moser T, Starr A. Auditory neuropathy-neural and synaptic mechanisms. Nat Rev Neurol 2016;12:135-49.  Back to cited text no. 5
    
6.
Lepcha A, Chandran RK, Alexander M, Agustine AM, Thenmozhi K, Balraj A. Neurological associations in auditory neuropathy spectrum disorder: Results from a tertiary hospital in South India. Ann Indian Acad Neurol 2015;18:171-80.  Back to cited text no. 6
[PUBMED]  [Full text]  
7.
Gantt S, Bitnun A, Renaud C, Kakkar F, Vaudry W. Diagnosis and management of infants with congenital cytomegalovirus infection. Paediatr Child Health 2017;22:72-4.  Back to cited text no. 7
    
8.
Foulon I, Vleurinck L, Kerkhofs K, Gordts F. Hearing configuration in children with cCMV infection and proposal of a flow chart for hearing evaluation. Int J Audiol 2015;54:714-9.  Back to cited text no. 8
    
9.
Baerts W, Van Straaten HL. Auditory neuropathy associated with postnatally acquired cytomegalovirus infection in a very preterm infant. BMJ Case Rep 2010;2010: BMJ Case Rep.2010 Oct 12;2010:bcr0120102689. doi:10.1136/bcr.01.2010.2689.  Back to cited text no. 9
    
10.
Natale F, De Curtis M, Bizzarri B, Orlando MP, Ralli M, Liuzzi G, et al. Isolated auditory neuropathy at birth in congenital cytomegalovirus infection. Ital J Pediatr 2020;46:3.  Back to cited text no. 10
    


    Figures

  [Figure 1], [Figure 2]



 

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