Pachyonychia congenita is an autosomal disorder which affects keratin. Manifestations of this disorder is most often seen on the skin and fingernails. This is just a short presentation which mostly focuses on its pathogenesis. Please see other references for more information.

1. Pachyonychia Congenita
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2. DESCRIPTION
• Etymology
– Greek
• Pachy = “thick”
• Onyx = “nail”
– Latin
• Congenita = “born with”
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3. What is Pachyonychia
Congenita?
• An autosomal dominant condition that
primarily affects the nails & skin.
• Signs & symptoms usually become
apparent within few months of life
• Pachyonichia congenita tarda – a rare
form of the condition
– Appears in adolescence or early adulthood.
• This disorder does not affect lifespan, but
patients do experience constant pain.
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4. CLINICAL MANIFESTATIONS
• Hypertrophic nail dystrophy: A
hallmark of this disorder is
thickened & abnormally shaped
fingernails & toenails.
• Painful calluses & blisters:
Palms & the feet will have
painful blisters & calluses. 
makes it almost impossible for
the child to walk
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5. CLINICAL MANIFESTATIONS
• Palmoplantar keratoderma
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6. CLINICAL MANIFESTATIONS
• Follicular hyperkeratosis: Bumps around
hair follicles in areas that get lots of
friction: waist, hips, knees, elbows
• Oral leukokeratosis: thick, white patches
inside the mouth and on the tongue
• Palmoplantar hyperhidrosis: excessive
sweating on the palms & soles
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7. CLINICAL MANIFESTATIONS
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8. Less common features
• Angular cheilitis: sores at the corner of the
mouth
• Teeth at or before birth
• Laryngeal involvement with a white keratin
film on the larynx causing hoarseness or
breathing difficulties
• Intense pain on first bite: The pain is near the
jaw or ears & lasts 15-25 seconds when
beginning to eat or swallow
– More common in younger children & often
confused with ear problems.
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9. GENETIC CAUSES OF
PACHYONYCHIA CONGENITA
Etiology & Pathogenesis
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10. Loci
• The keratin genes are
located in two clusters
• Keratins are a family of
related proteins with
about 54 members.
• Keratins are proteins
that form tough fibers
that strengthen skin,
hair and finger nails.
• Only mutations in
keratins 6a, 6b, 16, and
17 are linked to PC
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11. • Normal keratin filaments form a strong structural
network (left) that enables cells to withstand
pressure and stretching. Mutant keratin proteins
form clumps (right), resulting in weak cells that
break open under pressure. Images courtesy Prof. W.H. Irwin McLean,
University of Dundee, Scotland. Keratin filaments are green, and cell nuclei are blue.
1/31/2015 Prepared by Dixi Dawn F. Apigo

12. KRT6A
KRT6 a gene
provides
instructions
for making
Keratin 6a
The keratin that gives the
tough framework to skin of the
palms & feet, nails, & the
mucous lining inside the mouth
K6A teams
with K16
To create dense
networks
Give strength & residency to the
skin & nails
K6A is also involved in
wound healing
KRT6A is located on the long arm (q) of chromosome
12 at position 13.13
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13. KRT6A Mutation
Over 20
mutations in PC-
1.
Most mutations involve only a single
AA protein building block
A few add or delete
genetic material
Change structure of K6A & disrupt the
creation of keratin filament network
Without functional
keratin
Skin & nails are
easily damaged
Painful & distorted
nails, skin, & other
symptoms
1/31/2015 Prepared by Dixi Dawn F. Apigo

14. KRT16
• Long arm (q) of chromosome 16 at position 21.2
KRT16
• Provides
instruction for
K16
K16
• Works with K6
• To make
strong, tough
keratin
intermediate
filaments
Keratin
intermediate
filaments
• Provide
strength &
resiliency to the
nails, skin &
other tissues
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15. KRT16 Mutations
Over 13 mutations in
KRT16 cause PC-1
Most cases: the
condition is present at
birth or recognized
soon after
Most mutations occur
in the exchange of
only 1 amino acid
building block
A few mutations may
delete a few amino
acids
The changes disrupt
the assembly
pathways of keratin
1/31/2015 Prepared by Dixi Dawn F. Apigo

16. KRT6B
• Long arm (q) of chromosome 12 at position 13.13
KRT6B instructs
K6b
K6b
- is found in the
tough fibrous
framework of cells
that form skin, hair,
& nails
- Also found in the
sweat glands
K6b joins with
keratin 7 to
form keratin
intermediate
filaments
1/31/2015 Prepared by Dixi Dawn F. Apigo

17. KRT6B Mutations
Without proper keratin structure
Soles of the feet become very fragile &
blister easily, & nails do not function
properly
Sweat glands are also affected & leads to
the development of cysts
Mutations disrupt
the work with keratin 17 the creation of the keratin network
2 mutations in KRT6B cause PC-2
Change only 1 amino acid building block Delete the genetic material
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18. KRT17
• Locus 17q21.2
KRT17
instructs for
the protein
K17
Produced in
the nails, hair
follicles, skin
on the palms
& soles,
sweat glands
or
sebaceous
glands
K17
partners
with K6 to
make the
proper
keratin
structure
that are
tough &
resilient
1/31/2015 Prepared by Dixi Dawn F. Apigo

19. KRT17 Mutations
About 16 mutations in
KRT17 cause PC-2
Most mutations are the
result of only 1 amino
acid building block
Alteration in the
structure of K-17 keeps
it from working
effectively with K-6b
Mutations disrupt the
filament network
Leading to a breakdown in the skin cells,
formation of cysts, & malfunction of the nails
& hair follicle cells
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20. Diagnosis & Management
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21. Diagnosis
• Usually by its clinical appearance
• Skin biopsy of affected tissue show only
nonspecific changes
• Molecular genetic testing – to detect the
affected keratin genes
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22. Classification of PC based on clinical
manifestations
PC-1 Pachyonychia
Congenita Type 1
• Has most of the features
listed
• Related to mutations in
two genes:
1. KRT6A
2. KRT16
PC-2 Pachyonychia
Congenita Type 2
• Has additional features
• Development of cysts,
called steatocytomas, all
over the body.
• Coarse, twisted & brittle
hair
• Some babies may be
born with prenatal teeth
1. KRT6B
2. KRT17
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23. Classification of PC based on keratin
gene with specific mutation
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24. Treatment
• Effectiveness of treatment depends on the
severity of the specific problem
• Treatment might include:
– Emollients – soften the skin
– Keratolytics eg salicylic acid ointment (for
treatment of scaly skin diseases), urea cream (a
natural moisturizing factor) or other forms of heel
balm
– Mechanical debridement
– Pain relief
– Oral retinoids eg acitretin
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25. References
• Genetic Learning Center. Pachyonychia congenita.
Retrieved from
http://learn.genetics.utah.edu/content/disorders/single
gene/pc/
• Kelly, E.B. (2013). Encyclopaedia of human genetics
and disease. Santa Barbara, California: ABC-CLIO,
LLC
• Pachyonychia Congenita Project: What is
pachyonychia congenita? Retrieved from
http://www.pachyonychia.org/what_is_pc.php
• DermNet NZ. (2014). Pachyonychia congenita.
Retrieved from
http://www.dermnetnz.org/scaly/pachyonychia.html
1/31/2015 Prepared by Dixi Dawn F. Apigo