Introduction
Cornelia de Lange syndrome (CdLS) is a rare genetic polymalformation condition, described
by Brachmann in 1916 and by de Lange in 1933, who observed distinct facial traits,
upper and/or lower limb abnormalities, intellectual disability, and other associated
malformations (cardiac, gastrointestinal, and musculoskeletal) in individuals with
the condition.[1]
[2]
[3] It has a broad clinical spectrum, ranging from mild phenotypes to severe conditions,
which may lead to death.[4]
The incidence estimates range from 1:10 thousand to 1:30 thousand live births. The
exact incidence rate is unknown because many mild cases tend to be underreported.
Most cases result from genetic mutations, equally affecting both sexes, and occurring
in all races and ethnicities.[1]
[4]
The diagnosis of CdLS is established in two ways: through clinical findings of the
classic phenotypic characteristics of CdLS and/or through the identification of a
variant heterozygous pathogen in the NIPBL, RAD2, SMC3, and BRD4 genes, or a pathogenic homozygous variant in the HDAC8 or SMC1A genes. The rates of these variations are as follows: NIPBL – 80%; SMC1A – 5%; HDAC8–4%; SMC3–1 to 2%; and RAD21 and BRD4– < 1%;[5] or by identifying the altered gene, which can be performed through a sequential
molecular genetic test of a single gene, be it NIPBL, SMC1A, HDAC8, SMC3, RAD21 or BRD4, that is, if the individual has a very characteristic SCdL phenotype and in the initial
search variations in the NIPBL gene are not found, one should consider of the SMC1A, SMC3, RAD21, HDAC8, or BRD4 genes. All sequences will be searched, one by one, from mild to severe phenotypes.[5]
In cases in which it is more difficult to surmise CdLS from observation of the phenotypic
features alone, comprehensive genomic testing (which does not require the clinician
to determine which genes are likely to be involved) is performed. The technique most
widely used is whole exome sequencing (WES), which has been designed to identify and
analyze the sequence of all protein-coding genes in the genome. The exome comprises
only 1 to 2% of the human genome, but it contains most of the currently-recognized
disease-causing variants.[5]
As aforementioned, CdLS is a rare syndrome that usually encompasses multiple impairments.
Hence, individuals with CdLS may present hearing changes such as outer-, middle-,
or inner-ear malformations. Therefore, hearing loss may also be present in various
cases, as many genes that can cause genetic hearing loss and be transmitted by autosomal
dominant (15%), autosomal recessive (80%), sex-related (2–3%), and mitochondrial patterns
(1–2%) have been cataloged.[6]
[7]
[8]
According to the first international consensus statement,[8] the hearing loss is very common (with rates ranging from 85–90%) in individuals
with CdLS, present from childhood, and predominantly bilateral. Conductive hearing
loss may be present in 75% of the cases, and sensorineural hearing loss, in 25% of
the cases, ranging from mild to severe (40–50%). Sensorineural hearing loss has reported
in 45% of adults with CdLS.[8]
The etiology of conductive hearing loss in CdLS is usually stenosis of the external
auditory canal, middle-ear ossicular anomalies, acute or chronic otitis media, and
the presence of nonspecific soft tissue filling the middle ear. The possible causes
of sensorineural hearing loss are inner-ear anomalies, such as cochlear dysplasia.[8]
[9]
[10]
Both conductive and sensorineural hearing losses negatively impact development, particularly
that of language, which requires multidisciplinary practices, including routine audiological
examinations.[11] Possible surgical (such as ventilation tubes) or nonsurgical treatments must also
be considered, as well as the indication, selection, and fitting of hearing aids to
potentialize speech and language development, with early intervention in the case
of children. As for adults, early intervention aims to improve the interactions among
relatives and make communication effective in the workplace, thus maximizing the quality
of life of individuals with CdLS.[11]
Nonetheless, to date, little is known about audiological profiles in CdLS.[12] Hence, the auditory pathway must be thoroughly investigated, encompassing its peripheral
and central portions. Also, since various procedures are used, the most indicated
ones must be identified to reach precise diagnoses and guide future studies.
Thus, the objective of the present study was to characterize the audiological profile
of individuals with CdLS through behavioral, electroacoustic, and electrophysiological
assessments.
Results
Sample Characterization
[Table 1] shows the characterization of the sample in terms of age, gender, and genetic analysis
of individuals with SCdL.
Table 1
Sample characterization regarding age group, sex, and gene of individuals with Cornelia
de Lange syndrome
|
Mean
|
Standard deviation
|
Minimum
|
Maximum
|
|
Age (in years)
|
12.38
|
± 7.40
|
3
|
26
|
|
Number of participants (N)
|
Percentage (%)
|
|
Sex
|
|
|
|
Male
|
9
|
69.23%
|
|
Female
|
4
|
30.77%
|
|
Total
|
13
|
100%
|
|
Gene
|
|
|
|
NIPBL
|
12
|
92.30%
|
|
SMC1A
|
1
|
7.70%
|
|
Total
|
13
|
100%
|
Pure-Tone Audiometry
[Table 2] shows a descriptive analysis of the auditory thresholds obtained in each frequency
of the Pure-Tone Audiometry (PTA). No statistically significant differences were found
between the right and left ears regarding the mean hearing thresholds at 250 to 8 kHz
in the PTA.
Table 2
Descriptive analysis of hearing thresholds per frequency obtained with pure-tone threshold
audiometry and comparison between right and left ears in individuals with Cornelia
de Lange syndrome
|
Ear
|
N
|
Mean
(dB HL)
|
Standard deviation
|
Minimum
|
Quartile 1
|
Median
|
Quartile 3
|
Maximum
|
W-value
|
p-value+
|
|
0.25 kHz
|
RE
|
8
|
18.13
|
9.23
|
5.00
|
10.00
|
20.00
|
27.50
|
30.00
|
7.00
|
0.2402
|
|
LE
|
8
|
20.63
|
12.66
|
5.00
|
6.25
|
22.50
|
33.75
|
35.00
|
|
0.5 kHz
|
RE
|
8
|
20.00
|
15.12
|
0.00
|
5.00
|
22.50
|
33.75
|
40.00
|
0.00
|
0.0719
|
|
LE
|
8
|
22.50
|
15.81
|
5.00
|
5.00
|
25.00
|
38.75
|
40.00
|
|
1 kHz
|
RE
|
8
|
21.25
|
14.33
|
0.00
|
6.25
|
27.50
|
30.00
|
40.00
|
7.50
|
0.8875
|
|
LE
|
8
|
21.25
|
13.30
|
5.00
|
6.25
|
25.00
|
32.50
|
40.00
|
|
2 kHz
|
RE
|
8
|
24.38
|
14.25
|
5.00
|
10.00
|
27.50
|
38.75
|
40.00
|
9.00
|
0.4299
|
|
LE
|
8
|
21.25
|
16.20
|
0.00
|
5.00
|
25.00
|
37.50
|
40.00
|
|
3 kHz
|
RE
|
8
|
21.25
|
14.58
|
0.00
|
6.25
|
25.00
|
35.00
|
35.00
|
4.00
|
0.4076
|
|
LE
|
8
|
19.38
|
15.68
|
0.00
|
1.25
|
25.00
|
32.50
|
40.00
|
|
4 kHz
|
RE
|
8
|
21.88
|
14.87
|
5.00
|
5.00
|
25.00
|
35.00
|
40.00
|
0.00
|
0.0719
|
|
LE
|
8
|
19.38
|
15.68
|
0.00
|
1.25
|
22.50
|
35.00
|
35.00
|
|
6 kHz
|
RE
|
8
|
23.75
|
14.33
|
5.00
|
10.00
|
25.00
|
38.75
|
40.00
|
14.00
|
0.928
|
|
LE
|
8
|
23.75
|
15.06
|
5.00
|
6.25
|
27.50
|
38.75
|
40.00
|
|
8 kHz
|
RE
|
8
|
23.75
|
14.82
|
5.00
|
6.25
|
30.00
|
35.00
|
40.00
|
3.00
|
0.1198
|
|
LE
|
8
|
20.63
|
12.37
|
5.00
|
6.25
|
25.00
|
30.00
|
35.00
|
Abbreviations: dB HL, decibel – hearing level; LE, left ear; RE, right ear.
Note:
+
p-value obtained through the Wilcoxon test.
Regarding the type of hearing loss in the PTA, 60% of the patients had bilateral conductive
hearing loss, and the other 40% had conductive and sensorineural hearing loss concurrently.
As for the distribution per ear in CdLS patients, the PTA found 62.50% of changes
in the right ear and 62.5% in the left ear. All hearing losses identified through
PTA were mild (N = 5 in the right ear and N = 5 in the left ear).
Speech Audiometry
In the speech audiometry, which was only performed in eight patients, the SRT and
SRPI results were found to be compatible with those of the PTA in all cases.
An inferential analysis was made in these speech tests as well, to compare the right
and left ears. However, no statistically significant differences were found (SRT:
p = 0.6374/ SRPI: p = 1.000).
Acoustic Immittance Measures
The tympanometry results were classified as normal and abnormal per ear (right and
left) in individuals with CdLS, with 53.85% presenting abnormal results in the right
ear, and 69.24%, in the left ear.
Type-B tympanometry was presented by 85.72% in the right ear and by 88.89% in the
left ear, and type-C tympanometry, by 14.28% in the right ear. and by 11.11% in the
left ear. There was no association between abnormal results and ear laterality (Pearson
Chi-squared test [χ2] = 0.650; p = 0.420). There was no association between the ears and the type of tympanometry
curve change (χ2 = 0.686; p = 0.710).
Concerning ipsilateral and contralateral acoustic reflexes, responses were absent
in 11 (84.6%) individuals. Only 2 (15.4%) subjects presented bilateral responses.
Auditory Brainstem Response
Regarding the ABR, [Table 3] shows a descriptive analysis of the absolute latency values of waves I, III, and
V, and of interpeaks I to III, III to V, and I to V, as well as the electrophysiological
threshold.
Table 3
Descriptive and inferential analyses of the absolute latency values of waves I, III,
and V, interpeak intervals I to III, III to V, and I to V, and ABR Threshold
|
Ear
|
N
|
Mean
|
Standard deviation
|
Minimum
|
Quartile 1
|
Median
|
Quartile 3
|
Maximum
|
W-value
|
p-value+
|
|
Wave I
|
RE
|
12
|
1.74
|
0.36
|
1.43
|
1.52
|
1.64
|
1.85
|
2.75
|
16.00
|
0.275
|
|
LE
|
12
|
1.84
|
0.31
|
1.45
|
1.63
|
1.72
|
2.15
|
2.40
|
|
Wave III
|
RE
|
12
|
3.85
|
0.25
|
3.69
|
3.70
|
3.78
|
3.87
|
4.60
|
16.50
|
0.084
|
|
LE
|
12
|
4.01
|
0.35
|
3.62
|
3.71
|
3.94
|
4.34
|
4.70
|
|
Wave V
|
RE
|
12
|
5.67
|
0.25
|
5.45
|
5.55
|
5.60
|
5.68
|
6.40
|
12.00
|
0.034*
|
|
LE
|
12
|
5.84
|
0.33
|
5.45
|
5.54
|
5.84
|
6.07
|
6.57
|
|
Interpeak interval I–III
|
RE
|
12
|
2.12
|
0.18
|
1.83
|
1.95
|
2.18
|
2.27
|
2.35
|
24.50
|
0.476
|
|
LE
|
12
|
2.16
|
0.14
|
1.95
|
2.04
|
2.14
|
2.29
|
2.40
|
|
Interpeak interval III–V
|
RE
|
12
|
1.82
|
0.07
|
1.70
|
1.79
|
1.81
|
1.85
|
1.97
|
30.00
|
0.823
|
|
LE
|
12
|
1.83
|
0.19
|
1.52
|
1.63
|
1.89
|
1.97
|
2.12
|
|
Interpeak interval I–V
|
RE
|
12
|
3.94
|
0.17
|
3.65
|
3.85
|
3.94
|
4.08
|
4.18
|
30.50
|
0.529
|
|
LE
|
12
|
3.99
|
0.14
|
3.80
|
3.87
|
4.00
|
4.15
|
4.18
|
|
ABR threshold
|
RE
LE
|
12
12
|
36.67
39.58
|
14.35
16.02
|
20.00
20.00
|
20.00
22.50
|
40.00
40.00
|
50.00
50.00
|
60.00
70.00
|
2.50
|
0.203
|
Abbreviations: ABR, auditory brainstem response; LE, left ear; RE, right ear. Notes:
*Statistically significant difference; +
p-value obtained through the Wilcoxon test.
The comparison of the results of the right and left ears through the Wilcoxon test
revealed a difference between them only in the absolute latency of wave V in the ABR.
The left ear presented higher values than those of the right ear (p = 0.034).
[Table 4] shows the qualitative analysis of the ABRs, which were classified as normal or abnormal
in the right and left ears of individuals with SCdL.
Table 4
Qualitative analysis of the ABR (normal or abnormal) and p-value of the association between the right and left ears in individuals with Cornelia
de Lange syndrome (N = 12)
|
Ear
|
Normal
|
Abnormal
|
Chi-squared
|
p-value+
|
|
Wave I
|
RE
|
75.00%
|
25.00%
|
1.600
|
0.206
|
|
LE
|
50.00%
|
50.00%
|
|
Wave III
|
RE
|
83.33%
|
16.67%
|
1.815
|
0.178
|
|
LE
|
50.00%
|
50.00%
|
|
Wave V
|
RE
|
91.67%
|
8.33%
|
2.459
|
0.104
|
|
LE
|
50.00%
|
50.00%
|
|
Interpeak interval I–III
|
RE
|
100.00%
|
0.00%
|
Ө
|
Ө
|
|
LE
|
100.00%
|
0.00%
|
|
Interpeak interval III–V
|
RE
|
100.00%
|
0.00%
|
Ө
|
Ө
|
|
LE
|
91.67%
|
8.33%
|
|
Interpeak interval I–V
|
RE
|
100.00%
|
0.00%
|
Ө
|
Ө
|
|
LE
|
100.00%
|
0.00%
|
|
ABR threshold
|
RE
LE
|
33.33%
25.00%
|
66.67%
75.00%
|
0.202
|
0.653
|
Abbreviations: ABR, auditory brainstem response; LE, left ear; RE, right ear.
Notes: Ө: the analysis could not be performed because the samples were too similar; +
p-value obtained through the Pearson Chi-squared test.
No statistically significant difference was found regarding the changes in the absolute
latencies of waves I, III, and V and interpeak intervals I-III, III-V, and I-V, and
the ABR threshold between right and left ears.
Discussion
In the present study, we assessed 13 individuals with CdLS – 12 with a genetic diagnosis
of NIPBL variant (92.30%), and 1 with a diagnosis of SMC1A variant (7.70%), as shown in [Table 1].
The PTA could only be performed in 8 out of the 13 individuals, and hearing loss was
detected in 5 of them (62.50%), as shown in [Tables 2] and [3]. Some studies have found a an incidence of hearing loss ranging from 60 to 67% in
subjects assessed through PTA,[9]
[20] whereas other similar studies found that hearing loss affected 80% of the individuals
with CdLS.[5]
[10]
[11]
[21] This demonstrates an unequal occurrence of hearing loss in the population in question.
Many factors, such as the gene variant and the level of organic or cognitive impairment,
are believed to interfere with this divergence.
As for the type, there were 3 cases of bilateral conductive hearing loss (60% of the
patients with hearing loss) and 2 cases of right-ear sensorineural and left-ear conductive
hearing loss (40% of the cases of hearing loss). Thus, all individuals presented conductive
hearing loss, most of them bilaterally. Likewise, studies[11]
[21] have found conductive hearing loss in 60% and 59.1% of the cases. Elaborating on
the audiological findings, genetic diagnoses, and clinical severity of the individuals
with CdLS, some studies[21] highlighted the association with conductive hearing loss in a considerable number
of individuals with more severe phenotypes (NIPBL variant), corroborating the findings of the present study, in which this variant
and type of hearing loss were predominant. This can be explained by the findings of
middle-ear impairments in individuals with CdLS, particularly due to soft-tissue malformations
or fluid present in the middle-ear cavity.[9]
[10] Some authors[21] have stated that middle-ear impairments in individuals with CdLS may be associated
with NIPBL mutations, as no NIPBL mutation was found in normal hearing individuals – although they pointed out that
further studies assessing new variants identified in CdLS are needed to confirm this
finding.
Some treatment options, such as drugs and/or ventilation tubes, can be approached
to minimize the negative impacts of conductive hearing loss. However, they are not
always reliable clinical resources for these individuals because some of them have
middle-ear malformations (soft-tissue lesions) – rather than fluid effusion, which
usually takes place in secretory otitis media –, verified through imaging examinations
and in intraoperative conditions.[10] Hence, the possible conductive hearing loss etiologies in this population include
stenosis of the external auditory canal, middle-ear ossicular anomalies, nonspecific
middle-ear anomalies (nonspecific soft tissues filling the middle ear), and acute
or chronic otitis media.[12]
Sensorineural hearing loss corresponded to 40% of the types verified in the present
study, all of them unilateral and coexisting with contralateral conductive hearing
loss. This corroborates to some extent the findings of another study,[12] which verified sensorineural hearing loss in 40.3% of the cases. However, the authors[12] reported that sensorineural hearing loss was the most common impairment in CdLS,
followed by conductive hearing loss – which does not agree with the data obtained
in the present research.[12] Neither was sensorineural hearing loss the most frequent type in other studies,
corresponding to 22.7%[21] and 33.3%[20] of the cases, slightly below what was found in the present study. According to some
authors,[12] the possible sensorineural hearing loss etiologies in this population include inner-ear
malformations, such as cochlear dysplasia.
Regarding the degree, the present study verified bilaterally mild hearing loss through
PTA in all cases, corroborating the findings of other studies[9]
[11]
[21]
[22]
[23] in which mild hearing loss also predominated. However, other authors[20]
[24]
[25] found moderately severe hearing loss as the most frequent one, while another study[26] verified profound hearing loss to be prevalent (about 90% of the cases).
Such relevant variability in the degree of hearing loss may be explained when considering
that CdLS is rather heterogeneous and that, though individuals may have the same genetic
diagnosis, their phenotypic expressions are complex and diversified. It is known that
the more severe the phenotypic expression in an individual with CdLS, the more systems
and/or organs may be affected – and auditory structures are more likely to be impaired
in such cases. Hence, the greater occurrence of mild hearing loss may be explained
by the individuals' milder phenotypes and cognitive conditions to understand and respond
to what they were asked in the PTA, suggesting that their changes in auditory structure
were likewise milder.
Speech test results in speech audiometry were compatible with PTA results, indicating
that the audiometry was reliably conducted. The SRPI did not suggest retrocochlear
impairments, confirming the other findings of predominant middle-ear changes.
Tympanometry was conducted in all 13 study patients. Of these, 53.85% presented changes
in the right ear, and 69.24%, in the left ear. The main change found was the type-B
tympanometry curve (85.72% of right-ear and 88.89% of left-ear changes), followed
by the type-C curve (14.28% of right-ear and 11.11% of left-ear changes), which, in
2 individuals, were only found in 1 ear.
Few studies have described the results of acoustic immittance measures. One of them[10] took such measures from 14 individuals with CdLS, finding type-B tympanometry curves
in 13 of them (92.85%).
The occurrence of type-B tympanometry curves in both the present and other studies[10]
[11]
[21]
[23]
[27] corroborates the type of hearing loss most frequently found in this population (conductive),
as previously reported.
The Acoustic reflex results were compatible with the changes found in the tympanometry.
Only two of the studies[22]
[27] that verified acoustic immittance measures reported data on acoustic reflexes: one[22] described bilaterally present acoustic reflexes, corroborating mild sensorineural
hearing loss, and the other[27] described a case of bilaterally-absent reflexes due to middle-ear impairment (type-B
tympanometry curve).[27]
In CdLS, middle-ear impairment commonly results from malformations and/or nonspecific
tissues in the cavity, not necessarily from fluids present in the middle ear. Further
studies with complementary imaging diagnoses are also needed to identify possible
cases of treatable changes (otitis media caused by fluids present in the cavity).
The ABR results, regardless of the parameters analyzed, revealed abnormal latency
values in 8 (66.66%) of the 12 individuals assessed. Bilateral change was observed
in 3 (37.50%) of them, and 5 presented unilateral change (62.50%).
The following changes were found in ABR: increased absolute latency in wave I (25%
in the right ear and 50% in the left ear), in wave III (16.67% in the right ear and
50% in the left ear), and in wave V (8.33% in the right ear and 50% in the left ear).
Changes in the interpeak interval III to V were only found in one case and only in
the left ear, whereas no changes in interpeak intervals I-III and I-V were found in
any of the cases ([Table 4]).
The change observed in interpeak interval III to V was a slight increase. However,
this is an isolated finding, as the interpeak interval I to V was normal. Thus, it
was not qualified as suggestive of changes in the upper brainstem.
Few studies[27]
[28] have described brainstem auditory pathway integrity analysis in individuals with
CdLS, as most of them only reported electrophysiological threshold findings.
In one of the studies,[28] the authors investigated auditory pathway integrity through ABR in two individuals
with CdLS. One of them presented normal latency in wave I and interpeak interval I
to V at 80 dBnHL, while, in the other one, responses were absent at 100 dBnHL. Since
they did not find any external acoustic meatus or tympanic membrane abnormalities,
the authors[28] concluded that the first case was of mild sensorineural hearing loss, and the second,
of profound sensorineural hearing loss; however, other audiological procedures would
be necessary to confirm these findings.
In a case study,[27] the authors found increased absolute latencies in waves I, III, and V, and normal
interpeak intervals, bilaterally, in the ABR results. In the acoustic immittance measures,
they found type-B tympanometry curve and absent acoustic reflexes, bilaterally, confirming
the conductive hearing loss.[27] Hence, further studies with ABR in this population are needed to investigate possible
impairments in brainstem auditory pathway integrity – which, in combination with other
tests, may help reach a better audiological diagnosis.
[Table 3] shows a statistically significant difference between the right and left ears only
for the absolute latency of wave V – with higher values in the left ear. This may
be due to the more tympanometry curve changes (type B) in the left ear, characterizing
middle-ear changes and causing absolute latency delay in ABR.
As aforementioned, ABR changes in individuals with CdLS may be due to middle-ear impairments.
In the present study, one individual had increased absolute latencies in waves I,
III, and V, and normal interpeak intervals, bilaterally, while four individuals had
the same condition unilaterally – all of them with tympanometry curves of types B
and C.
Moreover, two individuals had decreased latency of wave I, with a tympanometry type-A
curve. This finding could be hypothetically compared with studies in individuals with
Down syndrome (DS) who have decreased latency values of waves I, III, and V in the
ABR, either having or not hearing loss.[29]
There is no consensus in the literature about what causes precocious ABR latency values
in DS. One of the various hypotheses is that the smaller head circumference decreases
the distance between the cochlea and the brainstem.[30] Therefore, a similar situation can be supposed in individuals with CdLS, as they
have some craniofacial traits, including microcephalia, like those of individuals
with DS.[5] Studies[30] in individuals with DS also suggest possible early brainstem myelination, auditory
pathway change or simplification, and/or greater nervous fiber conduction speed and
smaller brainstem – which can apply to some cases of CdLS as well.
The present study also verified that four individuals presented perfectly normal absolute
latencies of waves I, III, and V, and interpeak intervals, two of them, bilateral,
and two, unilateral, but with a type-B tympanometric curve. Hence, it can be deduced
that middle-ear impairments delayed the absolute latency of the waves, but, since
they are naturally precocious, the conditions in certain cases of CdLS may have led
to normal latency values. Hence, middle-ear conditions must be investigated to adequately
interpret ABR normal latency values in individuals with CdLS.
There is not satisfatory investigation about the peripheral and central auditory pathway
in individuals with SCdL. The full evaluation of the auditory system is a differencial
for this study.
Most studies[12] on SCdL found hearing loss in this population of patients, predominantly conductive
hearing loss, followed by sensorineural hearing loss, which corroborates the results
of the present study, in which conductive hearing loss was the most frequent finding.
This finding could be confirmed with the use of different procedures to compose the
audiological evaluation battery, since certain procedures cannot be performed in the
population in question, usually due to the intellectual impairment they present.
Still, mild hearing loss was predominantly found in the present study, corroborating
the findings of other studies,[9]
[11]
[21]
[22]
[23] which indicate that approximately one third of the individuals present mild hearing
loss.
Regarding the establishment of more advisable audiological procedures for this population,
we emphasize that, in cases of more severe phenotypic expressiveness, these patients
may benefit from objective evaluation methods, mainly acoustic immittance measures
to verify middle-ear conditions, and ABR electrophysiological threshold to verify
the degree of auditory impairment, since PTA is not always feasible due to behavioral
and IQ alterations.
Also, as aforementioned, SCdL is a rare genetic disease, with little-known and previously
researched conditions. Most of the research[9]
[22]
[23]
[24]
[25]
[26]
[27]
[28] has relied on case studies, and, as SCdL presents heterogeneity within the population
itself (although NIPBL individuals present variation in the same gene, for example, they may present different
phenotypes, from milder to severe), it is difficult to find similar data to group
the patients.
Thus, hearing loss in individuals with SCdL should be a concern and not be accepted
merely as an alteration inherent to the syndrome. Therefore, the need for early assessment,
otorhinolaryngological and audiological follow-up, and intervention in individuals
with SCdL is highlighted, from routine audiological examinations to strategies to
treat hearing loss.
Early intervention will enable the development of language and auditory skills, providing
a better quality of life for individuals with SCdL and their families in all aspects:
verbal, cognitive, social and professional.
To rule out the impairments that hearing loss can cause in individuals with SCdL,
it is important to develop public policy guidelines on the subject. Therefore, there
must be a wide range of diagnostic tests: PTA, ABR and acoustic immittance measures
and, if any alteration is detected, these individuals can be referred for the use
of: hearing aid device (HAD), bone-anchored hearing aid (BAHA), and cochlear implant
(CI), because, according to research,[12] some degree of success has been obtained when using these devices.
The limitations of the present study include the small sample size, as it is a rare
syndrome. Additionally, many individuals invited to participate lived in other states,
making their attendance difficult; adherence to the study was further impacted by
the COVID-19 pandemic. Moreover, some individuals had difficulties performing all
procedures because of specific issues of the syndrome, such as IQ and behavioral changes.
