International Journal of Pediatric Otorhinolaryngology 95 (2017) 69e71

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International Journal of Pediatric Otorhinolaryngology

journal homepage: http://www.ijporlonline.com/

Case Report

Bilateral cochlear implantation in a child with Johanson Blizzard

Syndrome
Meredith A. Holcomb*, Habib G. Rizk, Nevitte S. Morris, Ted A. Meyer
Department of Otolaryngology-Head and Neck Surgery, Medical University of South Carolina, United States

a r t i c l e i n f o a b s t r a c t

Article history: Sensorineural hearing loss (SNHL) occurs in more than 80% of cases of Johanson Blizzard Syndrome (JBS).
Received 27 December 2016 However, limited knowledge exists in medical literature of cochlear implantation (CI) outcomes in
Received in revised form children with JBS. We report the case of a 5 year-old male with JBS and bilateral CI. While minimal
31 January 2017
progress in spoken language scores was noted after 4 years of bilateral CI use, substantial improvements
Accepted 3 February 2017
Available online 6 February 2017
in discrimination of speech sounds and audibility of spoken language and environmental sounds were
documented. Cochlear implantation is an available treatment option of profound SNHL in children with
JBS even if spoken language outcomes are marginal.
Keywords:
Johanson Blizzard Syndrome
© 2017 Elsevier B.V. All rights reserved.
Cochlear implantation
Speech outcomes
Sensorineural hearing loss

1. Introduction implants by age 16 months.

Johanson Blizzard Syndrome (JBS) was first described in 1971
[1]. Incidence is estimated to be 1 in 250,000 [2], and pancreatic
insufficiency is the most prominent feature of this syndrome [3].
Other clinical features include hypothyroidism in 40%, sensori-
neural hearing loss in >80%, short stature in >80%, developmental
delay and intellectual disability in 77%, imperforate anus in 39%,
genitourinary abnormalities in 38%, and craniofacial abnormalities
such as a small 'beak shaped' nose, long and narrow upper lip, small
pointed chin, dental abnormalities, and midline scalp defects [3].
JBS is inherited in an autosomal recessive pattern with a mutation
in the ubiquitin E3 ligase (UBR1) gene [4].
To date, more than 20 cases of deafness in patients with JBS have
been documented in medical literature, but with regards to out-
comes with cochlear implantation in JBS, only one report exists in
Russian literature [5] and none in the US literature. Presently, no
studies exist on speech development for children with JBS and
hearing loss. The objective of the present case study is to present
audiological management and speech/language results of a 5 year-
old male (Fig. 1) with JBS and profound bilateral sensorineural
hearing loss (SNHL) who received sequential bilateral cochlear
* Corresponding author. 135 Rutledge Ave, MSC 550, Charleston, SC, 29425-5500,
United States.
E-mail address: holcombm@musc.edu (M.A. Holcomb).
2. Case report
2.1. Audiological history
A 3-month-old male with JBS was evaluated in our clinic
following bilateral referral on his newborn hearing screen. He was
diagnosed with profound SNHL via auditory brainstem response
(ABR) test before age 4 months. He began an unsuccessful hearing
aid trial at age 5 months. A combination of visual reinforcement
audiometry and behavioral observation audiometry was used over
several months for continued audiological management. Due to his
developmental delays, it was difficult to obtain reliable behavioral
test results, therefore, a second ABR test was completed to confirm
the diagnosis of profound SNHL. His parents reported limited aided
responses with hearing aids and the child was subsequently
referred for a CI evaluation. Magnetic resonance imaging (MRI) of
the cochlea and internal auditory canals was unremarkable.
Sequential CI surgery occurred at 13 and 16 months of age with
Med El Concert Standard internal arrays. Both surgeries were un-
complicated Initial CI programming proved to be difficult given his
developmental delays, absent electrical stapedial reflex threshold
(ESRT) responses, and inconsistent test results in the sound booth.
A relatively flat MAP was used for programming and M levels were
in an average range. By age 3 years, a reliable CI audiogram was
obtained using Conditioned Play Audiometry.

http://dx.doi.org/10.1016/j.ijporl.2017.02.001
0165-5876/© 2017 Elsevier B.V. All rights reserved.
70 M.A. Holcomb et al. / International Journal of Pediatric Otorhinolaryngology 95 (2017) 69e71

thresholds with each CI in the borderline normal to mild hearing

loss range (25e35 dB HL) for frequencies of 250e6000 Hz (Table 1).
Hearing results with each CI were substantially better than pre-
operative unaided results which were in the profound hearing
loss range. Speech awareness thresholds for each CI were 25 dB HL
when means he was able to detect speech in a borderline normal
hearing range. Overall, his hearing results with bilateral CI proved
he had good audibility to all sounds in the speech spectrum.

2.4. Speech/language results

Following 3 years of bilateral CI use, he increased his expressive

Fig. 1. Facial features of JBS in our patient: nasal alae hypoplasia, abnormal hair
pattern, and narrow upper lip (with permission from parents).
2.2. Speech/language history
From the onset of hearing loss diagnosis, the family chose to
pursue oral communication for their child. Auditory Verbal Therapy
(AVT) began at 6 months of age and the family attended weekly AVT
sessions with consistent carry-over in the home. The parents
routinely videotaped the child at home to demonstrate his
responsiveness to sounds, including speech, in his natural envi-
ronment. He was enrolled in an oral preschool program at age 3
years, yet his spoken language development continued to be
extremely delayed after a full academic year in this setting. Bian-
nual speech/language evaluations were completed using the
Preschool-Language Scale version 5 (PLS-5).
language score by 11 months and his receptive language score by
only 6 months according to the Preschool-Language Scale 5. At that
time he was enrolled in a Total Communication classroom where
both American Sign Language (ASL) and spoken language were
used. His parents began learning ASL as well. After 12 months of
using Total Communication, the child improved 5 months in his
expressive language skills and 6 months in his receptive language
skills. And, in the 4 years since his second CI, his language age has
improved 1 year, 4 months expressive and 1 year receptive (Fig. 2).
While his spoken vocabulary continues to be limited, his ASL skills
have progressed well and, presently, he uses more than 50 spon-
taneous signs in addition to signing numbers, colors, and ABC's. His
Categories of Auditory Performance (CAP) score increased from
0 pre-op to 4, which indicates he can now discriminate at least two
speech sounds. His Speech Intelligibility Rating (SIR) increased
from 0 to 2 as connected speech is unintelligible and intelligible
speech is developing in single words when context and lip reading
cues are available. Overall, he has extreme difficulty with process-
ing spoken language, but his communication with ASL is flourish-
ing, and he is able to respond to speech stimuli and environmental
sounds using his CIs.

2.3. Audiological results 3. Discussion

His most recent ear-specific CI audiogram demonstrated hearing More than 20 cases of deafness in patients with JBS have been

Table 1
Post-operative hearing thresholds with right and left cochlear implants (results listed in dB HL).

Implanted ear 250 Hz 500 Hz 1000 Hz 2000 Hz 3000 Hz 4000 Hz 6000 Hz SAT

Right 35 30 35 35 30 25 35 25
Left 30 30 25 30 30 25 30 20

Fig. 2. Age equivalent scores for the Preschool Language Scales, 5th Edition are plotted over child's age at the time of assessment.
 M.A. Holcomb et al. / International Journal of Pediatric Otorhinolaryngology 95 (2017) 69e71
documented in medical literature but little is mentioned about the
treatment of the underlying hearing loss. Several reports state
hearing aids were used following hearing loss diagnosis [6e8] and
two reports mention use of CI [5,9]. Only one article, accessible in
Russian literature and unable to be translated, reports outcomes of
CI use in this population [5]. Presently, no studies exist on speech
development for children with JBS and hearing loss. Children with
hearing loss and other disabilities are at great risk for substantial
communication difficulties. Their communication needs are
extensive and their rehabilitation programs are often complex.
Cochlear implantation can provide adequate access to sound,
including speech detection and environmental sound awareness.
However, development of spoken language is not always achieved.
Patients with JBS typically present with moderate to severe in-
tellectual disability, yet normal intelligence was reported in two
cases [10,11]. Unfortunately, the level of intelligence of our child is
unknown. In cases of patients with JBS who undergo cochlear im-
plantation, the severity of the patient's intellectual disability will
likely negatively impact their spoken language outcomes, as it does
with other syndromic deaf children and/or children with multiple
disabilities. Post-CI speech and language improvements have been
noted for deaf children with mild cognitive delays, yet gains were
reduced relative to their normal hearing peers [12]. However, CI
continues to be recommended in cases where there is less likeli-
hood of spoken language development as studies have shown that
children with varying levels of intellectual disability benefit from CI
use [13e17].
In 2000, Waltzman et al. evaluated 31 profoundly deaf children
with a wide range of documented impairments in addition to
deafness, including CHARGE Syndrome, Waardenburg Syndrome,
Usher's Syndrome, Austism, and Cerebral Palsy. The average speech
perception scores of the children with multiple disabilities were
lower than those of the control group without additional disabil-
ities, and fewer of the children with multiple disabilities were able
to complete the speech task. However, the group with multiple
disabilities did display improvements in speech perception
following CI. Overall post-CI benefit was perceived in areas of social
interaction and connectedness to the environment for the children
with multiple disabilities [16].
In 2008, Berretini and colleagues reported post-implant out-
comes of 23 profoundly deaf children with neuropsychiatric dis-
orders and found positive results in the areas of speech perception,
communication abilities, and improved quality of life. They sug-
gested a multidisciplinary approach of combined qualitative and
quantitative standardized measures is necessary with this popu-
lation as post-implant outcome results are often variable with
children with multiple disabilities [17].
Given the little information known about children with JBS who
have undergone CI, this syndrome should not be considered a
contraindication for surgery. Our case report supports cochlear
implantation as an appropriate treatment for profound SNHL in
children with JBS even when spoken language outcomes are mar-
ginal as it is evident the child does benefit from access to sound.
While audiological management and speech therapy sessions will
not always be straight-forward for children with JBS, early identi-
fication and treatment of the subsequent hearing loss is of great
importance to rehabilitate the patient to better meet
71
communication needs.
Conflicts of interest
MAH e Advanced Bionics Audiology Advisory Council.
Funding
This research did not receive any specific grant from funding
agencies in the public, commercial, or not-for-profit sectors.
Acknowledgements
The authors are grateful to the child and his family for their
participation in this project.
References
[1] A. Johanson, R. Blizzard, A syndrome of congenital aplasia of the alae nasi,
deafness, hypothyroidism, dwarfism, absent permanent teeth, and malab-
sorption, J. Pediatr. 79 (1971) 982e987.
[2] M. Baraitser, S.V. Hodgson, The Johanson-Blizzard syndrome, J. Med. Genet. 19
(1981) 302e303.
[3] M. Zenker, J. Mayerle, A. Reis, M.M. Lerch, Genetic basis and pancreatic biology
of Johanson-Blizzard syndrome, Endocrinol. Metab. Clin. North Am. 35 (2006)
243e253 (vii-viii).
[4] M. Zenker, J. Mayerle, M.M. Lerch, A. Tagariello, et al., Deficiency of UBR1, a
ubiquitin ligase of the N-end rule pathway, causes pancreatic dysfunction,
malformations and mental retardation (Johanson-Blizzard syndrome), Nat.
Genet. 37 (2005) 1345e1350.
[5] T. Chugunova, V.V. Bakhshinian, T.G. Markova, M.V. Goikhburg,
V.V. Zherenkova, Johanson-Blizzard syndrome: audiological features and re-
sults of cochlear implantation, Vestn. Otorinolaringol. 2 (2014) 90e92
(Russian).
[6] F. Rosanowski, U. Hoppe, T. Hies, U. Eysholdt, Johanson-Blizzard syndrome. A
complex dysplasia syndrome with aplasia of the nasal alae and inner ear
deafness, HNO 46 (1998) 876e878.
[7] A. Sismanis, I.A. Polisar, M.L. Ruffy, J.C. Lambert, Rare congenital syndrome
associated with profound hearing loss, Arch. Otolaryngol. 105 (1979)
222e224.
[8] S. Aubrey, B. Crroks, M. Rashid, Pancytopenia from severe cobalamin (vitamin
B12) deficiency in Johanson-Blizzard syndrome, Eur. J. Clin. Nutr. 67 (2013)
1118.
[9] M. Elting, A. Kariminejad, M.L. de Sonnaville, J. Ottenkamp, S. Bauhuber,
B. Bozorgmehr, M. Zenker, J.M. Cobben, Johanson-Blizzard syndrome caused
by identical UBR1 mutations in two unrelated girls, one with a cardiomyop-
athy, Am. J. Med. Genet. A 146A (2008) 3058e3061.
[10] J.B. Moeschler, M.S. Lubinsky, Johanson-Blizzard syndrome with normal in-
telligence, Am. J. Med. Genet. 22 (1985) 69e73.
[11] T. Atik, M. Karakoyun, M. Sukalo, M. Zenker, F. Ozkinay, S. Aydoodu, Two novel
UBR1 gene mutations ın a patient with Johanson Blizzard Syndrome: a mild
phenotype without mental retardation, Gene 570 (2015) 153e155.
[12] R.F. Holt, K.I. Kirk, Speech and language development in cognitively delayed
children with cochlear implants, Ear Hear 26 (2005) 132e148.
[13] Y.M. Lee, L.S. Kim, S.W. Jeong, J.S. Kim, S.H. Chung, Performance of children
with mental retardation after cochlear implantation: speech perception,
speech intelligibility, and language development, Acta Oto-Laryngologica 130
(2010) 924e934.
[14] H.Y. Youm, I.J. Moon, E.Y. Kim, Y.S. Cho, W.H. Chung, S.H. Hong, The auditory
and speech performance of children with intellectual disability after cochlear
implantation, Acta Oto-Layngologica 133 (2013) 59e69.
[15] J. Hamzavi, W.D. Baumgartner, B. Egelierler, P. Franz, B. Schenk, W. Gstoettner,
Follow up of cochlear implanted handicapped children, Int. J. Pediatr. Oto-
rhinolaryngol. 56 (2000) 169e174.
[16] S.B. Waltzman, V. Scalchunes, N.L. Cohen, Performance of multiply handi-
capped children using cochlear implants, Am. J. Otol. 21 (2000) 329e335.
[17] S. Berrettini, F. Forli, E. Genovese, R. Santarelli, E. Arslan, A.M. Chilosi, et al.,
Cochlear implantation in deaf children with associated disabilities: challenges
and outcomes, Int. J. Audiol. 47 (2008) 199e208.