Omim Entry - # 173650 - Kindler Syndrome
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7232019 Omim Entry - 173650 - Kindler Syndrome
httpslidepdfcomreaderfullomim-entry-173650-kindler-syndrome 13
SNOMEDCT 238836000 ORPHA 306539173650
KINDLER SYNDROME
Alternative titles symbols
POIKILODERMA HEREDITARY ACROKERATOTIC
BULLOUS ACROKERATOTIC POIKILODERMA OF KINDLER AND WEARY
POIKILODERMA CONGENITAL WITH BULLAE WEARY TYPE
Phenotype‑Gene Relationships
Clinical Synopsis
TEXT
A number sign () is used with this entry because Kindler syndrome can be caused by homozygous mutation in the FERMT1 (KIND1) gene (607900)
on chromosome 20p13
Description
Kindler syndrome is an autosomal recessive dermatosis characterized by congenital blistering skin atrophy photosensitivity skin fragility and
scaling (summary by Jobard et al 2003)
Clinical Features
Kindler (1954) described an English girl with unusual congenital blistering of her hands and feet Later in childhood the patient developed reticulate
erythema and diffuse cutaneous atrophy beginning in sun‑exposed areas Her gums bled easily and the skin of the dorsal hands and feet had a thin
wrinkled appearance By 10 years of age the blistering and sun sensitivity had resolved but the skin remained thin and fragile (Siegel et al 2003)
Weary et al (1971) described a disorder which they named hereditary acrokeratotic poikiloderma in 10 members of a white kindred Expression
was highly variable and fell into 4 categories (1) vesicopustule formation which remains confined to the hands and feet beginning from 1 to 3
months of age and resolving in late childhood (2) widespread eczematoid dermatitis somewhat resembling atopic eczema starting between ages 3
and 6 months and completely resolving by age 5 years (3) gradual appearance of diffuse poikiloderma with striate and reticulate atrophy which
spares only the face scalp and ears and persists into adulthood and (4) development of keratotic papules on the hands feet elbows and knees
which first appear at varying times before 5 years of age and persist indefinitely Male‑to‑male transmission was observed Larregue et al (1981)
reviewed 3 pedigrees supporting autosomal dominant inheritance They stated that a pigmentary anomaly is present in about 90 of cases
Hacham‑Zadeh and Garfunkel (1985) suggested autosomal recessive inheritance They described 2 related Kurdish Jewish sibships each with first‑
cousin parents 1 was affected in the first sibship and 3 were affected in the second The proposita had had bullae on pressure areas from birth These
healed with atrophic scars She also had severe photosensitivity on exposed areas and developed widespread poikiloderma Bullae did not occur
after age 17 years Oral examination showed limitation of mouth opening ankyloglossia dental overbite and atrophy of buccal mucosa with white
spots
Jobard et al (2003) described 5 consanguineous families from North Africa with Kindler syndrome All affected family members exhibited congenital
blistering progressive poikiloderma ichthyosis and xerosis Variable clinical findings among the families included photosensitivity palmoplantar
keratoderma oral mucosal involvement syndactyly and stenosis of mucosal openings
Siegel et al (2003) identified a group of 26 Native American patients with Kindler syndrome all younger than 40 years of age who were members of
a tribe in the Bocas del Toro province on the northwestern Caribbean coast of Panama The patients showed congenital acral blisters blistering after
trauma or sun exposure erythema and itching after sun exposure and patchy hyper‑ and hypopigmentation with atrophy and telangiectases
(poikiloderma) developing in early childhood in both sun‑exposed and nonexposed skin Other features included hyperkeratosis of the palms and
soles and diffuse cutaneous atrophy and wrinkling particularly on the dorsa of the hands and feet Other mucocutaneous features included
periodontal disease dental caries and phimosis Typically the blistering and photosensitivity improved markedly in adulthood but the
poikiloderma persisted There was some variability in phenotypic severity particularly in the degree of photosensitivity age at onset of
Location Phenotype Phenotype
MIM number
Inheritance
(in progress)
Phenotype
mapping key
GeneLocus GeneLocus
MIM number
20p123 Kindler syndrome 173650 AR 3 KIND1 607900
7232019 Omim Entry - 173650 - Kindler Syndrome
httpslidepdfcomreaderfullomim-entry-173650-kindler-syndrome 23
poikiloderma and degree of hyperkeratosis Siegel et al (2003) noted that Kindler syndrome clinically resembles both inherited blistering skin
disorders such as dystrophic epidermolysis bullosa (226600) and congenital poikilodermas such as Rothmund‑Thomson syndrome (268400)
Mapping
Jobard et al (2003) performed a genomewide linkage analysis in 5 North African families with Kindler syndrome and narrowed the disease interval
to an 834‑kb region on chromosome 20p123 Siegel et al (2003) confirmed the location of this locus in the Panamanian families and in individuals
with Kindler syndrome from diverse geographic backgrounds some of whom had previously been described (Wiebe et al 1996 Shimizu et al 1997
Suga et al 2000 Al Aboud et al 2002)
Genetic Heterogeneity
Siegel et al (2003) studied 2 families with Kindler syndrome 1 from Canada previously reported by Haber and Hanna (1996) and the other from the
United States with 1 parent of European descent and the other of African descent who did not show linkage to 20p123 Siegel et al (2003) noted
however that both of these families showed clinical differences from the Panamanian kindred suggesting that they may have a disorder that is
clinically similar to but genetically distinct from Kindler syndrome
Molecular Genetics
In affected members of 4 consanguineous Kindler kindreds from North Africa Jobard et al (2003) characterized 4 homozygous mutations in the
kindlerin (FERMT1) gene (6079000001‑6079000004) Three of the 4 mutations were predicted to result in truncation of the protein with loss of FERM
and pleckstrin homology (PH) domains The authors determined that kindlerin is expressed in multiple tissues including skin and proposed that it
may play a role in cell adhesion processes via integrin signaling
In patients with Kindler syndrome from various ethnic backgrounds Siegel et al (2003) identified loss‑of‑function mutations in the KIND1 gene
(6079000005‑6079000006) Because KIND1 is a human homolog of the C elegans protein Unc112 a membrane‑associated structuralsignaling
protein that had been implicated in linking the actin cytoskeleton to the extracellular matrix (ECM) Siegel et al (2003) suggested that Kindler
syndrome is the first skin fragility disorder shown to be caused by a defect in actin‑ECM linkage rather than keratin‑ECM linkage
Pathogenesis
Heinemann et al (2011) demonstrated that kindlin‑1‑deficient keratinocytes respond to cell stress by upregulating the expression of several
cytokines which via paracrine communication launch an inflammatory response in the dermis with subsequent activation of fibroblasts and their
differentiation to myofibroblasts which secrete and deposit increased amounts of extracellular matrix proteins The data were consistent with a
model in which repeated cycles of epidermal cell stress cytokine secretion dermal inflammation and profibrotic processes underlie the
mucocutaneous fibrosis in Kindler syndrome
See AlsoAguade et al (1972) Wallach et al (1981)
REFERENCES
1 Aguade J P Herrero C Castello C A Grimalt F Rueda Plata L A Congenital poikiloderma with vesicobullous lesions problems in
classification of hereditary poikilodermas Med Cutanea 6 417‑435 1972
2 Al Aboud K Al Hawsawi K Al Aboud D Al Githami A Kindler syndrome in a Saudi kindred Clin Exp Derm 27 673‑676 2002
[PubMed 12472544 related citations] [Full Text]
3 Haber R M Hanna W M Kindler syndrome clinical and ultrastructural findings Arch Derm 132 1487‑1490 1996 [PubMed 8961879
related citations] [Full Text]
4 Hacham‑Zadeh S Garfunkel A A Kindler syndrome in two related Kurdish families Am J Med Genet 20 43‑48 1985 [PubMed
3970073 related citations]
5 Heinemann A He Y Zimina E Boerries M Busch H Chmel N Kurz T Bruckner‑Tuderman L Has C Induction of phenotype
modifying cytokines by FERMT1 mutations Hum Mutat 32 397‑406 2011 [PubMed 21309038 related citations] [Full Text]
6 Jobard F Bouadjar B Caux F Hadj‑Rabia S Has C Matsuda F Weissenbach J Lathrop M Prudʹhomme J‑F Fischer J Identification
of mutations in a new gene encoding a FERM family protein with a pleckstrin homology domain in Kindler syndrome Hum Molec Genet
12 925‑935 2003 [PubMed 12668616 related citations] [Full Text]
7 Kindler T Congenital poikiloderma with traumatic bulla formation and progressive cutaneous atrophy Brit J Derm 66 104‑111 1954
7232019 Omim Entry - 173650 - Kindler Syndrome
httpslidepdfcomreaderfullomim-entry-173650-kindler-syndrome 33
NOTE OMIM is intended for use primarily by physicians and other professionals concerned wit h genetic disorders by genetics researchers and by advanced students in science and medicine While tOMIM database is open to the public users seeking information about a personal medical or genetic condition are urged to consult with a qualified physician for diagnosis and for answers to person
questions
OMIMreg and Online Mendelian Inheritance in Manreg are registered trademarks of the Johns Hopkins University
Copyrightreg 1966-2015 Johns Hopkins University
Update List
OMIM Entry Statistics
OMIM Gene Map Statistics
Register for Downloads
Register for API Access
Support OMIM
FAQ
Search Help
Linking Help
API Help
Copyright
Use Agreement
OMIM
Clinical Synopses
Gene Map
Hide Search Term Highlights
[PubMed 13149722 related citations]
8 Larregue M Prigent F Lorette G Canuel C Ramdenee P Acrokeratose poikilodermique bulleuse et hereditaire de Weary‑Kindler
Ann Derm Venerol 108 69‑76 1981
9 Shimizu H Sato M Ban M Kitajima Y Ishizaki S Harada T Bruckner‑Tuderman L Fine J‑D Burgeson R Kon A McGrath J A
Christiano A M Uitto J Nishikawa T Immunohistochemical ultrastructural and molecular features of Kindler syndrome distinguish it
from dystrophic epidermolysis bullosa Arch Derm 133 1111‑1117 1997 [PubMed 9301588 related citations] [Full Text]
10 Siegel D H Ashton G H S Penagos H G Lee J V Feiler H S Wilhelmsen K C South A P Smith F J D Prescott A R WessagowitV Oyama N Akiyama M and 30 others Loss of kindlin‑1 a human homolog of the Caenorhabditis elegans actin‑extracellular‑matrix
linker protein UNC‑112 causes Kindler syndrome Am J Hum Genet 73 174‑187 2003 [PubMed 12789646 images related citations] [Full
Text]
11 Suga Y Tsuboi R Hashimoto Y Yaguchi H Ogawa H A Japanese case of Kindler syndrome Int J Derm 39 284‑286 2000 [PubMed
10809978 related citations] [Full Text]
12 Wallach D Vignon‑Pennamen M‑D Cottenot F Poikilodermie congenitale avec bulles type Weary Ann Derm Venerol 108 79‑83 1981
13 Weary P E Manley W F Jr Graham G F Hereditary acrokeratotic poikiloderma Arch Derm 103 409‑422 1971 [PubMed 4253719
related citations] [Full Text]
14 Wiebe C B Silver J G Larjava H S Early‑onset periodontitis associated with Weary‑Kindler syndrome a case report J Periodont 67
1004‑1010 1996 [PubMed 8910840 related citations]
Contributors Marla J F OʹNeill ‑ updated 9142011
Creation Date Victor A McKusick 621986
Edit History carol 09142011
7232019 Omim Entry - 173650 - Kindler Syndrome
httpslidepdfcomreaderfullomim-entry-173650-kindler-syndrome 23
poikiloderma and degree of hyperkeratosis Siegel et al (2003) noted that Kindler syndrome clinically resembles both inherited blistering skin
disorders such as dystrophic epidermolysis bullosa (226600) and congenital poikilodermas such as Rothmund‑Thomson syndrome (268400)
Mapping
Jobard et al (2003) performed a genomewide linkage analysis in 5 North African families with Kindler syndrome and narrowed the disease interval
to an 834‑kb region on chromosome 20p123 Siegel et al (2003) confirmed the location of this locus in the Panamanian families and in individuals
with Kindler syndrome from diverse geographic backgrounds some of whom had previously been described (Wiebe et al 1996 Shimizu et al 1997
Suga et al 2000 Al Aboud et al 2002)
Genetic Heterogeneity
Siegel et al (2003) studied 2 families with Kindler syndrome 1 from Canada previously reported by Haber and Hanna (1996) and the other from the
United States with 1 parent of European descent and the other of African descent who did not show linkage to 20p123 Siegel et al (2003) noted
however that both of these families showed clinical differences from the Panamanian kindred suggesting that they may have a disorder that is
clinically similar to but genetically distinct from Kindler syndrome
Molecular Genetics
In affected members of 4 consanguineous Kindler kindreds from North Africa Jobard et al (2003) characterized 4 homozygous mutations in the
kindlerin (FERMT1) gene (6079000001‑6079000004) Three of the 4 mutations were predicted to result in truncation of the protein with loss of FERM
and pleckstrin homology (PH) domains The authors determined that kindlerin is expressed in multiple tissues including skin and proposed that it
may play a role in cell adhesion processes via integrin signaling
In patients with Kindler syndrome from various ethnic backgrounds Siegel et al (2003) identified loss‑of‑function mutations in the KIND1 gene
(6079000005‑6079000006) Because KIND1 is a human homolog of the C elegans protein Unc112 a membrane‑associated structuralsignaling
protein that had been implicated in linking the actin cytoskeleton to the extracellular matrix (ECM) Siegel et al (2003) suggested that Kindler
syndrome is the first skin fragility disorder shown to be caused by a defect in actin‑ECM linkage rather than keratin‑ECM linkage
Pathogenesis
Heinemann et al (2011) demonstrated that kindlin‑1‑deficient keratinocytes respond to cell stress by upregulating the expression of several
cytokines which via paracrine communication launch an inflammatory response in the dermis with subsequent activation of fibroblasts and their
differentiation to myofibroblasts which secrete and deposit increased amounts of extracellular matrix proteins The data were consistent with a
model in which repeated cycles of epidermal cell stress cytokine secretion dermal inflammation and profibrotic processes underlie the
mucocutaneous fibrosis in Kindler syndrome
See AlsoAguade et al (1972) Wallach et al (1981)
REFERENCES
1 Aguade J P Herrero C Castello C A Grimalt F Rueda Plata L A Congenital poikiloderma with vesicobullous lesions problems in
classification of hereditary poikilodermas Med Cutanea 6 417‑435 1972
2 Al Aboud K Al Hawsawi K Al Aboud D Al Githami A Kindler syndrome in a Saudi kindred Clin Exp Derm 27 673‑676 2002
[PubMed 12472544 related citations] [Full Text]
3 Haber R M Hanna W M Kindler syndrome clinical and ultrastructural findings Arch Derm 132 1487‑1490 1996 [PubMed 8961879
related citations] [Full Text]
4 Hacham‑Zadeh S Garfunkel A A Kindler syndrome in two related Kurdish families Am J Med Genet 20 43‑48 1985 [PubMed
3970073 related citations]
5 Heinemann A He Y Zimina E Boerries M Busch H Chmel N Kurz T Bruckner‑Tuderman L Has C Induction of phenotype
modifying cytokines by FERMT1 mutations Hum Mutat 32 397‑406 2011 [PubMed 21309038 related citations] [Full Text]
6 Jobard F Bouadjar B Caux F Hadj‑Rabia S Has C Matsuda F Weissenbach J Lathrop M Prudʹhomme J‑F Fischer J Identification
of mutations in a new gene encoding a FERM family protein with a pleckstrin homology domain in Kindler syndrome Hum Molec Genet
12 925‑935 2003 [PubMed 12668616 related citations] [Full Text]
7 Kindler T Congenital poikiloderma with traumatic bulla formation and progressive cutaneous atrophy Brit J Derm 66 104‑111 1954
7232019 Omim Entry - 173650 - Kindler Syndrome
httpslidepdfcomreaderfullomim-entry-173650-kindler-syndrome 33
NOTE OMIM is intended for use primarily by physicians and other professionals concerned wit h genetic disorders by genetics researchers and by advanced students in science and medicine While tOMIM database is open to the public users seeking information about a personal medical or genetic condition are urged to consult with a qualified physician for diagnosis and for answers to person
questions
OMIMreg and Online Mendelian Inheritance in Manreg are registered trademarks of the Johns Hopkins University
Copyrightreg 1966-2015 Johns Hopkins University
Update List
OMIM Entry Statistics
OMIM Gene Map Statistics
Register for Downloads
Register for API Access
Support OMIM
FAQ
Search Help
Linking Help
API Help
Copyright
Use Agreement
OMIM
Clinical Synopses
Gene Map
Hide Search Term Highlights
[PubMed 13149722 related citations]
8 Larregue M Prigent F Lorette G Canuel C Ramdenee P Acrokeratose poikilodermique bulleuse et hereditaire de Weary‑Kindler
Ann Derm Venerol 108 69‑76 1981
9 Shimizu H Sato M Ban M Kitajima Y Ishizaki S Harada T Bruckner‑Tuderman L Fine J‑D Burgeson R Kon A McGrath J A
Christiano A M Uitto J Nishikawa T Immunohistochemical ultrastructural and molecular features of Kindler syndrome distinguish it
from dystrophic epidermolysis bullosa Arch Derm 133 1111‑1117 1997 [PubMed 9301588 related citations] [Full Text]
10 Siegel D H Ashton G H S Penagos H G Lee J V Feiler H S Wilhelmsen K C South A P Smith F J D Prescott A R WessagowitV Oyama N Akiyama M and 30 others Loss of kindlin‑1 a human homolog of the Caenorhabditis elegans actin‑extracellular‑matrix
linker protein UNC‑112 causes Kindler syndrome Am J Hum Genet 73 174‑187 2003 [PubMed 12789646 images related citations] [Full
Text]
11 Suga Y Tsuboi R Hashimoto Y Yaguchi H Ogawa H A Japanese case of Kindler syndrome Int J Derm 39 284‑286 2000 [PubMed
10809978 related citations] [Full Text]
12 Wallach D Vignon‑Pennamen M‑D Cottenot F Poikilodermie congenitale avec bulles type Weary Ann Derm Venerol 108 79‑83 1981
13 Weary P E Manley W F Jr Graham G F Hereditary acrokeratotic poikiloderma Arch Derm 103 409‑422 1971 [PubMed 4253719
related citations] [Full Text]
14 Wiebe C B Silver J G Larjava H S Early‑onset periodontitis associated with Weary‑Kindler syndrome a case report J Periodont 67
1004‑1010 1996 [PubMed 8910840 related citations]
Contributors Marla J F OʹNeill ‑ updated 9142011
Creation Date Victor A McKusick 621986
Edit History carol 09142011
7232019 Omim Entry - 173650 - Kindler Syndrome
httpslidepdfcomreaderfullomim-entry-173650-kindler-syndrome 33
NOTE OMIM is intended for use primarily by physicians and other professionals concerned wit h genetic disorders by genetics researchers and by advanced students in science and medicine While tOMIM database is open to the public users seeking information about a personal medical or genetic condition are urged to consult with a qualified physician for diagnosis and for answers to person
questions
OMIMreg and Online Mendelian Inheritance in Manreg are registered trademarks of the Johns Hopkins University
Copyrightreg 1966-2015 Johns Hopkins University
Update List
OMIM Entry Statistics
OMIM Gene Map Statistics
Register for Downloads
Register for API Access
Support OMIM
FAQ
Search Help
Linking Help
API Help
Copyright
Use Agreement
OMIM
Clinical Synopses
Gene Map
Hide Search Term Highlights
[PubMed 13149722 related citations]
8 Larregue M Prigent F Lorette G Canuel C Ramdenee P Acrokeratose poikilodermique bulleuse et hereditaire de Weary‑Kindler
Ann Derm Venerol 108 69‑76 1981
9 Shimizu H Sato M Ban M Kitajima Y Ishizaki S Harada T Bruckner‑Tuderman L Fine J‑D Burgeson R Kon A McGrath J A
Christiano A M Uitto J Nishikawa T Immunohistochemical ultrastructural and molecular features of Kindler syndrome distinguish it
from dystrophic epidermolysis bullosa Arch Derm 133 1111‑1117 1997 [PubMed 9301588 related citations] [Full Text]
10 Siegel D H Ashton G H S Penagos H G Lee J V Feiler H S Wilhelmsen K C South A P Smith F J D Prescott A R WessagowitV Oyama N Akiyama M and 30 others Loss of kindlin‑1 a human homolog of the Caenorhabditis elegans actin‑extracellular‑matrix
linker protein UNC‑112 causes Kindler syndrome Am J Hum Genet 73 174‑187 2003 [PubMed 12789646 images related citations] [Full
Text]
11 Suga Y Tsuboi R Hashimoto Y Yaguchi H Ogawa H A Japanese case of Kindler syndrome Int J Derm 39 284‑286 2000 [PubMed
10809978 related citations] [Full Text]
12 Wallach D Vignon‑Pennamen M‑D Cottenot F Poikilodermie congenitale avec bulles type Weary Ann Derm Venerol 108 79‑83 1981
13 Weary P E Manley W F Jr Graham G F Hereditary acrokeratotic poikiloderma Arch Derm 103 409‑422 1971 [PubMed 4253719
related citations] [Full Text]
14 Wiebe C B Silver J G Larjava H S Early‑onset periodontitis associated with Weary‑Kindler syndrome a case report J Periodont 67
1004‑1010 1996 [PubMed 8910840 related citations]
Contributors Marla J F OʹNeill ‑ updated 9142011
Creation Date Victor A McKusick 621986
Edit History carol 09142011