Pendred syndrome is an autosomal recessive disorder characterized by congenital sensorineural deafness, goiter, and impaired iodide organification. It is caused by mutations in the SLC26A4 gene which encodes a protein that functions as a chloride-iodide transporter. Key features include bilateral deafness that is usually present at birth, development of a goiter during adolescence or adulthood, and imaging findings of an enlarged vestibular aqueduct and Mondini defect in the cochlea. Diagnosis is confirmed by identifying biallelic mutations in SLC26A4 in an individual with hearing loss and thyroid abnormalities. Long term monitoring is recommended due to risk of goiter

1. PENDRED SYNDROME
Dr.Yassin M Alsaleh

3. • 10 year old boy case of chronic
osteomylitis, deafness, found to have
goitre .
• Lab: showed euthyrodsim.
• Biopsy: showed follicular carcinoma.
• gene for SLC26A4 : negative.
Case scenario

4. • Pendred syndrome is an autosomal
recessive disorder characterized by
congenital sensorineural deafness,
goitre, and impaired iodide
organification.
Introduction

5. History
• In 1896 Vaughan Pendred
first described Pendred
syndrome as a
combination of congenital
deafness and goiter.

6. • Although this disease was described
more than a hundred years ago.
• it remains unknown to most
physicians in clinical practice, and
its diagnosis is certainly often
missed.
Introduction

7. • estimated incidence :
7.5 to 10 in 100,000 .
• This disorder may account to
approximately 10% of the cases of
hereditary deafness.
• Most common cause of syndromic
deafness
Epidemiology

8. Genetics
• Pendred syndrome is inherited as
an autosomal recessive trait .
• in many families consanguinity is
present.
• The phenotype of Pendred patients,
can vary within and between
families

9. • Pendred syndrome is caused by mutations
in the SLC26A4 gene (PDS gene) .
• The gene is located at chromosome 7 .
• Gene encodes a protein (pendrin) that
functions as a chloride, iodide transporter
• Up to now , more than 100 different
mutations in the PDS gene have been
discovered
Genetics

13. • In the absence of the transporter, iodine is
taken up normally by the thyrocyte, but is not
efficiently bound to thyroglobulin in the
colloid.
• gene is expressed in the thyroid gland, the
inner ear, and the kidney.
• Mutations in the SLC26A4 cause not only
classical PS but also an autosomal recessive
form of isolated deafness without thyroid
disease.
Genetics

14. • The mechanisms involved in goiter
formation in PS are not completely
understood
• It may include :
• transient increases in serum TSH in
response to low thyroid hormone synthesis
due to less efficient organification of
iodide
• increased iodide retention in thyrocytes.
Pathophysiology (goitre)

15. • increased deiodinase activities in
goiters of PS patients and the
resulting increased intrathyroidal
conversion of T4 into T3
Pathophysiology (euthyroidism)

16. • hearing impairment is the leading
manifestation .
• Always bilateral.
• although one ear may be more
severely affected than the other .
• The hearing impairment is of the
sensorineural type and is usually
severe.
presentation

17. • It is usually already present at birth
• typically comes to medical attention
through the absence or marked
delay of language development
(prelingually deaf).
presentation

18. • the other characteristic feature of
Pendred syndrome is thyroid
involvement, with goiter and
hypothyroidism.
• A defect of thyroid hormone synthesis
impairs the transport of iodide from
thyroid cells into the colloid.
presentation

19. • the thyroid abnormality is of highly
variable severity,
• it may be absent when the hearing
impairment is first diagnosed.
presentation

20. presentation
• most Pendred patients develop a goiter
during adolescence or adulthood.
• Although neonates with Pendred
syndrome rarely have goitre.
• approximately 75% of affected persons will
eventually develop a multinodular or
diffuse goiter
• Patients are usually euthyroid.

21. • Sometimes the goiter is large
enough to cause tracheal
compression.
presentation

22. diagnosis
hearing
impairment
euthyroid or
hypothyroid
goiter
Organification
defect

23. • The conclusive evidence of Pendred
syndrome:
• Disease-producing mutations in
both alleles of the SLC26A4/PDS
gene in a person with hearing
impairment and thyroid pathology
(goiter and/or hypothyroidism)
Diagnostic criteria for Pendred syndrome

24. LAB
• thyroid-stimulating hormone (TSH).
H,N.
• free thyroxine (fT4).N,L.
• the serum thyroglobulin .H,N.

25. Imaging
• computed tomography (CT) or magnetic
resonance tomography (MRT) :
• reveals an enlarged vestibular aqueduct
(EVA) in 85% to 100% of cases .
• Mondini deformity in Approximately 20%.

26. • They have a type of cochlear
malformation known as a Mondini
defect (cochlea).
• A Mondini malformation is
characterized by 1.5 coils instead of
2.5 coils.
Imaging

27. Axial CT scan of the petrous temporal bone in a patient with Pendred syndrome to show a
typical example of Mondini malformation (arrowed)

29. • thyroid ultrasonography :
• thyroid volume .
• any cysts .
• inflammatory or malignant diseases
of the thyroid gland.
• Annually US.
Imaging

30. • test is no more criteria for the diagnosis.
• In Pendred syndrome, as in other defects
of thyroid hormone synthesis, the test is
typically positive.
• is neither 100% specific nor 100%
sensitive.
• This test, therefore, is increasingly being
replaced by molecular genetic analysis
perchlorate discharge test

31. • Perchlorate inhibits NIS function
(sodium iodine symporter) eliminating
the iodine gradient which is required
for maintaining the iodine in the gland.
• This will results in a partial discharge of
radiolabelled iodide from the thyroid.
• indicating an impaired organification.
perchlorate discharge test

32. perchlorate discharge test
• In this test, radioactive iodide (I123) is given
orally .
• One hour later, perchlorate 600 mg
intravenously is administered.
• diffusion of inorganified iodine from the
thyroid gland is measured as a drop in thyroid
counting rate.
• An abnormal result is defined as a release of
>20% of the radioactive iodide taken up by
the thyroid gland.

33. • there are rare, usually sporadic
cases of Pendred syndrome in
which no mutations are found.
• This implies that other genetic
causes of Pendred syndrome may
be implicated.
Molecular diagnosis

34. Differential
• It has been recently demonstrated that
some families with features of PDS do not
have the inner ear malformations and
mutations in the PDS gene.
• This condition has been named as
“pseudo-Pendred syndrome” (pseudo-
PDS), and has been hypothesized to
• be of autoimmune origin.

35. • Although patients with TPO defect
do not usually have deafness, some
cases with both TPO defect and
hearing loss, have been reported
Differential

36. Malignant potintial
• Patient with Dyshormonogenetic
goiters may undergo malignant
transformation probably due to
prolonged stimulation by thyrotropin.
• In Pendred syndrome, the incidence
of thyroid cancer is estimated to be
about 1%.

37. • The most common histology of the
thyroid cancers arising from
dyshormonogenetic goiters in patients
with Pendred syndrome is follicular
carcinomas .
• follicular variant of papillary thyroid
carcinoma also reported.
• This is why the thyroid gland should
be periodically followed up with US.
Malignant potintial

38. treatment
• optimal treatment of patients with Pendred
syndrome requires collaboration of :
• Pediatricians.
• Endocrinologists.
• Geneticists.
• phoniatrists/pediatric audiologists.
• ENT specialists.
• and neuroradiologists.

39. Take home message
• regular follow-up by using thyroid
imaging is advicable in patients
with Pendred syndrome.