Congenital CMV infection and connexin 26 mutations in childhood deafness : intervention with early cochlear implantation

Hearing impairment (HI) is a common disability, which affects a significant proportion of the population. Early in life, however, the risk of acquiring a HI is low, with 0.2 % of all newborns having a permanent HI, and of these, 0.04 % have a severe or profound HI. Even if there are only a few children born with a permanent HI, the consequences can be devastating for their speech perception and spoken language development. Normal hearing children, start to hear and differentiate sounds already in the fifth month of pregnancy, and thereafter, their speech and language acquisition is intensive during the first years of life. If, however, a child with a HI is to have a chance to catch up with normal hearing children, in terms of spoken language acquisition, it is important to provide the child with the best possible auditory input at the earliest opportunity.

The two most common reasons for permanent childhood HI are congenital cytomegalovirus (cCMV) infection and Connexin 26 (Cx26) mutations. cCMV infection might give the child other disabilities, such as cognitive delay, cerebral palsy and visual impairment, in addition to the HI. For children with Cx26 mutations, additional disabilities are less common.

The aim of this thesis was to study the results after CI intervention in children with permanent HI, and especially, to examine the effect of implantation in infants. Moreover, the aim was to study children with cCMV infection and Cx26 mutations and to describe the additionally disabilities arising from a cCMV infection.

In the first study, 90 children with a variety of HIs, which were of unknown etiology and non-syndromic, were tested for cCMV infection. The dried blood spot (DBS) sample, taken in the newborn period, was analysed for CVM DNA. Of the 90 children, 18 (20%) tested positive for cCMV infection.

In the second study, 79 children, of whom the majority had severe to profound, non- syndromic HI, were tested for Cx26 mutations. Twenty-four of the 79 children (30 %) had two pathological Cx26 mutations.

In the third study, 26 children with a HI caused by cCMV infection and 13 children with a HI caused by Cx26 mutations were examined by a multidisciplinary team, with the intention of investigating how frequently additional disabilities were present. Among the children with cCMV infection, there were a high number of children with disturbed balance and in addition neurodevelopmental disabilities and feeding problems were also found. Many of these additional disabilities have not previously been associated with a cCMV infection. In the Cx26 group, such additional problems were not found.

In the fourth study, a cohort of 137 children with CIs, operated between 2002 and 2011 was described. When children were operated on before nine months of age, no language delay was apparent when compared with data for normal hearing children. Additionally, their speech intelligibility was rated high sooner than for children who received their implants at a later age. The children who received implants between 9 and 11 months of age, caught up with the children operated on before they were nine months old, within two to three years. When their vocabulary was tested, the children with implants introduced at 12-17 months of age, caught up at early school-age. Those implanted later, when 18 months old or more, did not, however, catch up with the children who had received implants when younger.

In conclusion, early CI intervention is of great importance for children born with profound HI, if the aim is to acquire age-equivalent spoken language development. In addition, knowledge about the child’s etiology is important for an appropriate early and correct HI diagnosis, and to identify possible additional disabilities. Based on this broader knowledge about the child with a HI, it will be possible to give the child and family tailored support.

List of scientific papers

I. Karltorp E, Hellström S, Lewensohn-Fuchs I, Carlsson-Hansén E, Carlsson P-I, Engman M-L. Congenital CMV infection - a common cause of hearing loss of unknown aetiology. Acta Paediatr. 2012 Aug;101(8):e357-62.
https://doi.org/10.1111/j.1651-2227.2012.02711.x

II. Carlsson P-I, Karltorp E, Carlsson-Hansén E, Åhlman H, Möller C, VonDöbeln U. GJB2 (Connexin 26) gene mutations among hearing-impaired persons in a Swedish cohort. Acta Otolaryngol. 2012 Dec;132(12):1301-5.
https://doi.org/10.3109/00016489.2012.701018

III. Karltorp E, Löfkvist U, Lewensohn-Fuchs I, Lindström K, Eriksson Westblad M, Teär Fahnehjelm K, Verrecchia L, Engman M-L. Impaired balance and neurodevelopmental disabilities in cochlear implanted children with cytomegalovirus-related hearing-loss. [Submitted]

IV. Karltorp E, Eklöf M, Freijd A, Östlund E, Asp F, Smeds H, Hellström S, Löfkvist U. Cochlear implantation before nine months of age is beneficial for the outcome of spoken language – a longitudinal study. [Manuscript]