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The Genodermatoses - An Overview - UpToDate
The Genodermatoses - An Overview - UpToDate
The Genodermatoses - An Overview - UpToDate
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All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Nov 2021. | This topic last updated: Jul 21, 2020.
INTRODUCTION
Basal cell nevus syndrome — The basal cell nevus syndrome (nevoid basal cell
carcinoma syndrome, Gorlin syndrome, MIM #109400) is a rare disorder of
autosomal dominant inheritance that results from germline mutations of the
human patched gene (PTCH). (See "Nevoid basal cell carcinoma syndrome (Gorlin
syndrome)".)
● Bifid ribs.
The histologic appearance of the BCCs in basal cell nevus syndrome does not differ
from those seen in sporadic cases. The diagnosis should be suspected in patients
who present with multiple BCCs, especially at an early age.
These patients require careful sun protection from infancy and regular skin
surveillance by a dermatologist. Radiotherapy should be avoided due to the risk of
inducing BCCs in the treatment fields.
The most characteristic skin feature is multiple epidermoid cysts. Other findings
include desmoid tumors, lipomas, osteomas (especially of the mandible),
supernumerary teeth, gastric polyps, and juvenile nasopharyngeal angiofibromas.
Congenital hypertrophy of the retinal pigmented epithelium is a reliable and early
marker of the disease when it is present. Prophylactic colectomy is recommended
because of the nearly universal development of colorectal cancer in affected
patients.
In addition to colorectal adenocarcinoma, patients with FAP are at risk for several
extracolonic malignancies, including:
Lentigines occur most commonly on the lips and perioral region (94 percent), hands
(74 percent), buccal mucosa (66 percent), and feet (62 percent) ( picture 2) [7].
They also occur on the nose, perianal area, and genitals and are rarely found in the
intestines. They usually occur during the first one to two years of life, increase in
size and number over the ensuing years, and finally fade after puberty, with the
exception of those on the buccal mucosa.
Gastrointestinal hamartomatous polyps are present in most patients with PJS, and
patients may develop gastrointestinal malignancy. The risk of nongastrointestinal
cancers, including adenocarcinomas of the breast, cervix, pancreas, uterus, and
ovaries, is also increased.
:
Hereditary leiomyomatosis and renal cell cancer — Hereditary leiomyomatosis
and renal cell cancer (HLRCC; MIM #150800) is caused by autosomal dominant,
heterozygous mutations in the fumarate hydratase gene (FH) [8]. HLRCC presents in
early adulthood with multiple cutaneous leiomyomas, most frequently on the trunk
and extremities ( picture 3A-D). Affected women frequently develop uterine
leiomyomas at an early age. HLRCC is associated with an increased risk of early-
onset, aggressive renal cancer [9]. (See "Hereditary leiomyomatosis and renal cell
cancer (HLRCC)".)
DISORDERS OF KERATINIZATION
Keratins are intermediate filament proteins that form the cytoskeleton in all
epithelial cells, including the stratified epithelium of the epidermis [11]. Keratins
represent the major proteins produced by the keratinocyte, which is the primary cell
type of the epidermis. The maturation of basal epidermal cells to the flattened cells
that constitute the superficial stratum corneum is known as keratinization [12].
Over 50 genes that encode keratins have been identified in humans [13]. The
phenotype resulting from a particular mutation depends upon the tissue-specific
expression pattern of that keratin.
:
Ichthyoses — The ichthyoses are a diverse group of hereditary skin disorders
characterized by the accumulation of "fish-like" scales resulting from abnormal
epidermal cell kinetics or differentiation ( table 2) [14]. The severity of the
individual disorders ranges from asymptomatic to life threatening.
The cornerstone of therapy for all types is aggressive hydration of the skin with
emollients. When tolerated, keratolytics also may be used. Severe or extensive
involvement may require systemic retinoids.
The major types of inherited ichthyoses are reviewed separately. Information for
patients and families is available on the website of the Foundation for Ichthyosis
and Related Skin Types.
The disorder typically presents in the second decade of life with hyperkeratotic,
yellow-brown, greasy-appearing papules that coalesce into verrucous-like plaques (
picture 5A-B) [23,24]. The lesions are often pruritic and frequently become
:
purulent and malodorous, especially if infected. Typical sites of involvement are in a
seborrheic distribution: trunk, face, scalp, and groin. Nails may demonstrate
red/white vertical stripes, subungual hyperkeratosis, and notching of the distal nail
margins ( picture 6). Palmar keratosis and pits often are present.
The course of the illness is chronic and persistent, with characteristic worsening in
summer months. Darier disease is discussed in detail separately. (See "Darier
disease".)
These disorders result from abnormalities in the cohesion of the layers of the
epidermis. They result in separation of the layers in response to minimal injury.
PIGMENTATION DISORDERS
Melanin, a black or brown pigment formed from tyrosine, is responsible for the
color of skin and hair [27]. Melanin is synthesized in melanocytes, which are
specialized, dendritic secretory cells derived from the neural crest. These cells
migrate to the basal layer of the epidermis during embryogenesis. The presence of
melanin in the epidermis helps provide protection from ultraviolet radiation.
:
Disorders include decreased and excessive pigmentation. Diagnosis is based on the
clinical features in most cases, although some may be clarified with molecular
testing. (See "Congenital and inherited hyperpigmentation disorders".)
Ocular albinism type 1 (OA1, MIM #300500), also known as Nettleship-Falls ocular
albinism, is the most common form of ocular albinism and has X-linked recessive
inheritance. It has an estimated prevalence of 1 in 50,000 to 150,000 live births
[32,33].
The clinical manifestations of OA1 are variable. In affected males, clinical features
may include mild cutaneous hypopigmentation, hypopigmentation of the iris and
retina, foveal hypoplasia, prominent choroidal vessels, nystagmus, strabismus, head
nodding, photophobia, impaired vision, and abnormal crossing of the optic fibers
resulting in deficient stereoscopic vision [31,34,35]. Female carriers may have a
patchy distribution of retinal pigmentation resulting from X-inactivation [31,36].
OA1 is diagnosed by careful analysis of the family pedigree for X-linked inheritance
and/or molecular analysis of the OA1 gene [36]. The severity of OA1 appears to be
related to ethnic background, with individuals from lightly pigmented racial groups
more severely affected than those from darkly pigmented groups [37-39]. Life
expectancy is normal [30].
OA1 has been associated with late-onset sensorineural deafness. This form (OASD,
:
MIM 300650) is probably a contiguous gene defect that includes the OA1 gene
[40,41]. Another form of ocular albinism with sensorineural deafness has been
linked to chromosome 11 and has autosomal recessive inheritance; this form is also
known as Waardenburg syndrome type 2 (MIM 103470) [42]. (See 'Waardenburg
syndrome' below.)
Ocular albinism type 2 (OA2, MIM #300600), also known as Forsius-Eriksson type
ocular albinism and Aland Island eye disease, is a rare, X-linked disorder with clinical
manifestations that include nystagmus, myopia, astigmatism, foveal hypoplasia,
reduced visual acuity, pigmentary changes in the retina, and changes in color vision;
the optic nerves are normal [30].
Waardenburg syndrome type 1 (MIM #193500) and type 3 (MIM #148820) are
caused by mutations in the gene for one of three transcription factors (PAX3),
whereas type 2 (MIM #193510) is caused by mutations in the transcription factor
MITF [50,51]. Waardenburg syndrome type 4 (MIM #277580) also has features of
Hirschsprung disease. This type is a result of biallelic mutation in the genes for the
endothelin-B receptor (EDNRB) or its ligand endothelin-B (EDN3) [52,53] or
heterozygous mutation in the SOX10 gene [54]. (See "Congenital aganglionic
megacolon (Hirschsprung disease)".)
NEUROCUTANEOUS SYNDROMES
The characteristic skin findings that contribute to establishing the diagnosis are:
It is estimated that more than 95 percent of patients with TSC have one of the
characteristic skin lesions [59]. The most common lesions are:
● Shagreen patches (connective tissue nevi), seen most commonly over the
lower trunk.
● A distinctive brown, fibrous plaque on the forehead, which may be the first and
most readily recognized feature of TSC to appear on physical examination of
affected neonates and infants ( picture 11) [59].
Patients with AT suffer from progressive cerebellar ataxia and other neurologic
abnormalities, oculocutaneous telangiectasias, and immune deficiency. Associated
features are an increased incidence of malignancy, radiation sensitivity, and
diabetes mellitus caused by insulin resistance. (See "Ataxia-telangiectasia".)
VASCULAR DISORDERS
The onset of the disorder varies from childhood to early adulthood, although the
characteristic skin findings may be subtle in children. The primary organ systems
involved include the skin, eyes, and cardiovascular systems; gastrointestinal
bleeding also can occur [64-66].
The primary ocular finding is that of angioid streaks, representing tears in Bruch's
membrane, but this finding is seen in other disorders as well ( picture 12E).
Macular degeneration and retinal deformities contribute to loss of central vision.
Severe vision loss occurs in 3 to 8 percent of patients.
The diagnosis of PXE is based upon the clinical appearance and findings on
histologic examination of lesional skin. Treatment consists of close ophthalmologic
management, monitoring and treatment of any cardiovascular symptoms, and
dietary consultation. Because of the risk of ocular disease, patients should be
educated to avoid contact sports and straining (eg, weight lifting) [66]. They should
be referred for genetic counseling.
:
X-LINKED DOMINANT DISORDERS
ECTODERMAL DYSPLASIAS
The ectodermal dysplasias are a large group of inherited disorders that manifest as
developmental anomalies in at least two of the structures derived from the
embryonic ectoderm, with at least one involving the skin appendages (hair, nails,
sweat glands) or teeth ( table 6) [69]. The classic ectodermal dysplasias, including
hypohidrotic ectodermal dysplasia, hypohidrotic ectodermal dysplasia with immune
deficiency, and hidrotic ectodermal dysplasia; tumor protein p63-related disorders;
and focal dermal hypoplasias are discussed separately.
SUMMARY
● Cutaneous findings are often a key to the diagnosis of the most common
neurocutaneous syndromes: neurofibromatosis ( picture 9A-C), tuberous
sclerosis complex (TSC) ( picture 10A-B), and ataxia-telangiectasia (AT). (See
'Neurocutaneous syndromes' above.)
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understanding keratin function. Trends Genet 2003; 19:278.
24. Burge SM, Wilkinson JD. Darier-White disease: a review of the clinical features in
163 patients. J Am Acad Dermatol 1992; 27:40.
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than meets the eye. Pigment Cell Res 2001; 14:243.
36. Oetting WS. New insights into ocular albinism type 1 (OA1): Mutations and
polymorphisms of the OA1 gene. Hum Mutat 2002; 19:85.
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39. Lyle WM, Sangster JO, Williams TD. Albinism: an update and review of the
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45. Dourmishev AL, Dourmishev LA, Schwartz RA, Janniger CK. Waardenburg
syndrome. Int J Dermatol 1999; 38:656.
46. Read AP, Newton VE. Waardenburg syndrome. J Med Genet 1997; 34:656.
47. Nayak CS, Isaacson G. Worldwide distribution of Waardenburg syndrome. Ann
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48. Silan F, Zafer C, Onder I. Waardenburg syndrome in the Turkish deaf
population. Genet Couns 2006; 17:41.
49. Hart J, Miriyala K. Neural tube defects in Waardenburg syndrome: A case report
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50. Potterf SB, Furumura M, Dunn KJ, et al. Transcription factor hierarchy in
Waardenburg syndrome: regulation of MITF expression by SOX10 and PAX3.
Hum Genet 2000; 107:1.
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causing Waardenburg syndrome. Hum Mutat 2010; 31:391.
52. Edery P, Attié T, Amiel J, et al. Mutation of the endothelin-3 gene in the
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53. McCallion AS, Chakravarti A. EDNRB/EDN3 and Hirschsprung disease type II.
Pigment Cell Res 2001; 14:161.
55. Gutmann DH, Aylsworth A, Carey JC, et al. The diagnostic evaluation and
:
multidisciplinary management of neurofibromatosis 1 and neurofibromatosis
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57. Lim JY, Kim H, Kim YH, et al. Merlin suppresses the SRE-dependent transcription
by inhibiting the activation of Ras-ERK pathway. Biochem Biophys Res Commun
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58. Kwiatkowski DJ, Short MP. Tuberous sclerosis. Arch Dermatol 1994; 130:348.
59. Webb DW, Clarke A, Fryer A, Osborne JP. The cutaneous features of tuberous
sclerosis: a population study. Br J Dermatol 1996; 135:1.
60. Ringpfeil F, McGuigan K, Fuchsel L, et al. Pseudoxanthoma elasticum is a
recessive disease characterized by compound heterozygosity. J Invest Dermatol
2006; 126:782.
61. Le Saux O, Urban Z, Tschuch C, et al. Mutations in a gene encoding an ABC
transporter cause pseudoxanthoma elasticum. Nat Genet 2000; 25:223.
62. Ringpfeil F, Lebwohl MG, Christiano AM, Uitto J. Pseudoxanthoma elasticum:
mutations in the MRP6 gene encoding a transmembrane ATP-binding cassette
(ABC) transporter. Proc Natl Acad Sci U S A 2000; 97:6001.
63. Bergen AA, Plomp AS, Schuurman EJ, et al. Mutations in ABCC6 cause
pseudoxanthoma elasticum. Nat Genet 2000; 25:228.
64. Sherer DW, Sapadin AN, Lebwohl MG. Pseudoxanthoma elasticum: an update.
Dermatology 1999; 199:3.
65. Engelman MW, Fliegelman MT. Pseudoxanthoma elasticum. Cutis 1978; 21:837.
66. Laube S, Moss C. Pseudoxanthoma elasticum. Arch Dis Child 2005; 90:754.
Inheritance/
Key clinical features
pathogenesis
Basal Cell Autosomal Multiple basal cell carcinomas. Other features include
Nevus dominant odontogenic cysts of the jaw, palmoplantar pits, bifid ribs
Syndrome and other skeletal abnormalities. Common CNS
Mutation of the
(Nevoid Basal abnormalites include calcification of the falx cerebri and
tumor
Cell bridging of the sella turcica. Extracutaneous tumors,
suppressor
Carcinoma including medulloblastomas, meningiomas, and ovarian
gene patched
Syndrome, fibrosarcomas, are also associated with the syndrome.
(PTC)
Gorlin
Syndrome)
Herlitz Autosomal Onset at birth with widespread bullae and erosions with
junctional recessive nonhealing granulation tissue; absent nails, dysplastic
EB teeth, oral lesions.
Mutations in the
laminin alpha-3, Increased risk of squamous cell carcinoma beginning in
beta-3, or adolescence.
gamma-2 gene
Hallopeau- Autosomal Onset at birth; generalized bullae that heal with extensive
Siemens recessive scarring; repeated episodes may lead to contraction
recessive flexures at the knees and elbows and fusion of the digits;
Mutation in the
dystrophic frequent involvement of the mucous membranes.
collagen type VII
EB
alpha-1 gene Increased risk of malignant melanoma beginning in
childhood and squamous cell carcinoma beginning in
adolescence.
Reproduced with permission from: Fitzpatrick TB, Johnson RA, Wolff K, Suurmond D.
Color Atlas & Synopsis of Clinical Dermatology. Common & Serious Diseases. (4th Ed).
McGraw-Hill, New York 2001. pgs. 268 & 289. Copyright © 2001 McGraw-Hill.
Reprinted with permission from Pounder RE, Allison MC, Dhillon AP. A Colour Atlas of
the Digestive System, Wolfe, London 1989 p. 118.
(A) Clustered, pink cutaneous leiomyomatosis nodules on the central and upper back.
Generalized cutaneous leiomyomatosis. Hundreds of painful, small, red papules and nodules on
the leg.
Inheritance
and Key clinical features
pathogenesis
Icthyosis vulgaris Autosomal Relatively common (1:250 to 1:300).
dominant Fine, white translucent scales
predominantly on extensor surfaces
Fillagrin defect
of extremities with sparing of
resulting in a
flexures, palms, soles, and face.
retention
Hyperlinear palms. Often associated
hyperkeratoses
with keratosis pilaris and atopy
(Normal including eczema. Onset during
epithelial childhood. Typically improves with
turnover) age.
Distal notching and linear, red and white bands are present on the
nails.
Site of Inheritance
cleavage Mutated gene
Subtypes Clinical features
within the Targeted gene
epidermis product
References:
:
1. Jonkman MF, Pasmooij AM, Pasmans SG, et al. Loss of desmoplakin tail causes lethal acantholytic
Epidermolysis bullosa. Am J HumGenet 2005; 77:653.
2. Hobbs RP, Han SY, van der Zwaag PA, et al. Insights from a desmoplakin mutation identified in lethal
acantholytic epidermolysis bullosa. J Invest Dermatol 2010; 130:2680.
3. Kim SJ, Ko JM, Shin SH, et al. Korean Monozygotic Twins with Lethal Acantholytic Epidermolysis Bullosa
Caused by Two Novel DSP Mutations. Ann Clin Lab Sci 2017; 47:213.
4. Bolling MC, Veenstra MJ, Jonkman MF, et al. Lethal acantholytic epidermolysis bullosa due to a novel
homozygous deletion in DSP: Expanding the phenotype and implications for desmoplakin function in skin
and heart. Br J Dermatol 2010; 162:1388.
5. Pigors M, Kiritsi D, Krümpelmann S, et al. Lack of plakoglobin leads to lethal congenital epidermolysis
bullosa: a novel clinico-genetic entity. Hum Mol Genet 2011; 20:1811.
6. Fine JD, Johnson L, Wright T. Epidermolysis bullosa simplex superficialis. A new variant of epidermolysis
bullosa characterized by subcorneal skin cleavage mimicking peeling skin syndrome. Arch Dermatol 1989;
125:633.
7. Kiritsi D, Cosgarea I, Franzke CW, et al. Acral peeling skin syndrome with TGM5 gene mutations may
resemble epidermolysis bullosa simplex in young individuals. J Invest Dermatol 2010; 130:1741.
8. Lanschuetzer CM, Fine JD. Classification and molecular basis of hereditary epidermolysis. In: Life with
Epidermolysis Bullosa (EB): Etiology, diagnosis, multidisciplinary care and therapy, Fine JD, Hintner H (Eds),
Springer, Vienna, New York 2008. p.6.
9. Fine JD. General cutaneous manifestations. In: Life with Epidermolysis Bullosa (EB): Etiology, diagnosis,
multidisciplinary care and therapy, Fine JD, Hintner H (Eds), Springer, Vienna, New York 2008. p.99.
10. Mellerio JE, Pulkkinen L, McMillan JR, et al. Pyloric atresia-junctional epidermolysis bullosa syndrome:
Mutations in the integrin beta4 gene (ITGB4) in two unrelated patients with mild disease. Br J Dermatol
1998; 139:862.
11. Nakano A, Pulkkinen L, Murrell D, et al. Epidermolysis bullosa with congenital pyloric atresia: novel
mutations in the beta 4 integrin gene (ITGB4) and genotype/phenotype correlations. Pediatr Res 2001;
49:618.
12. Pulkkinen L, Kim DU, Uitto J. Epidermolysis bullosa with pyloric atresia: Novel mutations in the beta4
integrin gene (ITGB4). Am J Pathol 1998; 152:157.
13. Maman E, Maor E, Kachko L, Carmi R. Epidermolysis bullosa, pyloric atresia, aplasia cutis congenita:
Histopathological delineation of an autosomal recessive disease. Am J Med Genet 1998; 78:127.
14. Groves RW, Liu L, Dopping-Hepenstal PJ, et al. A homozygous nonsense mutation within the dystonin gene
coding for the coiled-coil domain of the epithelial isoform of BPAG1 underlies a new subtype of autosomal
recessive epidermolysis bullosa simplex. J Invest Dermatol 2010; 130:1551.
15. McGrath JA, Stone KL, Begum R, et al. Germline Mutation in EXPH5 Implicates the Rab27B Effector Protein
Slac2-b in Inherited Skin Fragility. Am J Hum Genet 2012; 91:1115.
16. He Y, Maier K, Leppert J, et al. Monoallelic mutations in the translation initiation codon of KLHL24 cause skin
fragility. Am J Hum Genet 2016; 99:1395.
17. Lin Z, Li S, Feng C, et al. Stabilizing mutations of KLHL24 ubiquitin ligase cause loss of keratin 14 and
human skin fragility. Nat Genet 2016; 48:1508.
18. Lee JYW, Liu L, Hsu CK, et al. Mutations in KLHL24 Add to the Molecular Heterogeneity of Epidermolysis
Bullosa Simplex. J Invest Dermatol 2017; 137:1378.
Inheritance
Mutated
gene
Subtype Clinical features
Targeted
gene
product
JEB, localized Autosomal Localized disease of lesser extent and lesser severity,
recessive onset at birth; milia, nail dystrophy, and loss
Laminin-
alpha-3 chain
of laminin-332
Laminin-beta-
3 chain of
laminin-332
Laminin-
gamma-2
chain of
laminin-332
JEB, late onset Autosomal Mild form of JEB developing in young adulthood or
recessive later
References:
1. Fine JD, Eady RA, Bauer EA, et al. The classification of inherited epidermolysis bullosa (EB): Report of the
Third International Consensus Meeting on Diagnosis and Classification of EB. J Am Acad Dermatol 2008;
58:931.
2. Shabbir G, Hassan M, Kazmi A. Laryngo-onycho-cutaneous syndrome: A study of 22 cases. Biomedica 1986;
2:15.
3. Ainsworth JR, Spencer AF, Dudgeon J, et al. Laryngeal and ocular granulation tissue formation in two
Punjabi children: LOGIC syndrome. Eye (Lond) 1991; 5:717.
4. Ainsworth JR, Shabbir G, Spencer AF, Cockburn F. Multisystem disorder of Punjabi children exhibiting
spontaneous dermal and submucosal granulation tissue formation: LOGIC syndrome. Clin Dysmorphol
1992; 1:3.
5. Phillips RJ, Atherton DJ, Gibbs ML, et al. Laryngo-onycho-cutaneous syndrome: An inherited epithelial defect.
Arch Dis Child 1994; 70:319.
6. Murrell DF, Hamil K, Pfendner E, et al. Is Laryngo-Onycho-Cutaneous Syndrome a form of junctional
epidermolysis bullosa? Oral paper. Australasian College of Dermatologists' Spring Meeting, Cairns,
Australia, September 2005.
7. Figueira EC, Crotty A, Challinor CJ, et al. Granulation tissue in the eyelid margin and conjunctiva in
junctional epidermolysis bullosa with features of laryngo-onycho-cutaneous syndrome. Clin Exp
Ophthalmol 2007; 25:163.
8. Hamil K, Uitto J, Figueira EC, et al. Novel N-terminal mutation in LAMA3a isoform causing late-onset Herlitz
junctional epidermolysis bullosa with features of laryngo-onycho-cutaneous syndrome. Poster. Society for
Investigative Dermatology, Los Angeles, CA, May 2007.
9. Cohn HI, Murrell DF. Laryngo-onycho-cutaneous syndrome. Dermatol Clin 2010; 28:89.
10. Nicolaou N, Margadant C, Lilen MR, et al. Gain of glycosylation in integrin α3 causes lung disease and
nephrotic syndrome. J Clin Invest 2012; 122:4375.
11. Yalcin EG, He Y, Orhan D, et al. Crucial role of posttranslational modifications of integrin α3 in interstitial
lung disease and nephrotic syndrome. Hum Mol Genet 2015; 24:3679.
12. Has C, Spartà G, Kiritsi D, et al. Integrin α3 mutations with kidney, lung, and skin disease. N Engl J Med
2012; 366:1508.
Inheritance
Mutated
gene
Subtype Clinical features
Targeted
gene
product
Dominant DEB
Dominant DEB, Autosomal Predilection of blistering for hands and feet from
acral dominant, early infancy, milia, atrophic scarring, dystrophic (or
autosomal absent) nails
recessive
COL7A1
Type VII
collagen
Type VII
collagen
COL7A1
Type VII
collagen
COL7A1
Type VII
collagen
COL7A1
Type VII
collagen
Recessive DEB
Recessive DEB, Autosomal Blistering on hands and feet from early infancy,
localized recessive milia, atrophic scarring; nail dystrophy
COL7A1
Type VII
collagen
Type VII
collagen
Recessive DEB, Autosomal Pretibial and acral blistering at birth or from early
centripetalis recessive infancy, milia, atrophic scarring; nail dystrophy
Type VII
collagen
:
Recessive DEB, Autosomal Generalized blistering from birth or early infancy
bullous recessive that improves dramatically over time
dermolysis of Milia, atrophic scarring; dystrophic nails
COL7A1
the newborn
Type VII
collagen
References:
1. Dang N, Murrell DF. Mutation analysis and characterization of COL7A1 mutations with dystrophic
epidermolysis bullosa. Exp Dermatol 2008; 17:553.
2. Kim J, Loh CH, Murrell DF. Epidermolysis bullosa pruriginosa triggered by scabies infestation. J Dermatol
2013; 40:562.
3. Fine JD, Bruckner-Tuderman L, Eady RA. Inherited epidermolysis bullosa: updated recommendations on
diagnosis and classification. J Am Acad Dermatol 2014; 70:1103.
Inheritance
Mutated
Site of cleavage gene Clinical features
Targeted
gene product
Type of Encoding
MIM # Gene Locus Comments
albinism function
Original figure modified for this publication. From: Summers CG. Albinism. In: Taylor and Hoyt's Pediatric
Ophthalmology and Strabismus, 5th ed, Lambert SR, Lyons CJ (Eds), Elsevier, Atlanta 2017. Table used with the
permission of Elsevier Inc. All rights reserved.
Skin-colored and pink-tan, soft papules and nodules on the back are
neurofibromata. These lesions first appeared during late childhood.
The large, soft, ill-defined, subcutaneous nodule on the right lower
back is a plexiform neuroma. The café-au-lait macules appeared
earlier in childhood. A large one is visible on the middle lower back.
Reproduced with permission from: Fitzpatrick TB, Johnson RA, Wolff K, Suurmond D
(Eds). Color Atlas and Synopsis of Clinical Dermatology, 3 rd ed, McGraw-Hill, New
York. p.461. Copyright © 1997 The McGraw-Hill Companies.
Yellow papules are present on the inner aspect of the lower lip.
Infiltration of the buccal mucosa of the lip is the most common
mucous membrane involvement in pseudoxanthoma elasticum.
Reproduced with permission from: Gold DH, Weingeist TA. Color Atlas of the Eye in
Systemic Disease. Lippincott Williams & Wilkins, Baltimore 2001. Copyright © 2001
Lippincott Williams & Wilkins.
OMIM,
Ectodermal dysplasia (ED) whenever Inheritance
available
[3]
:
ED, Caratinga type [3] – AD?; XD?
ED, hypohidrotic, with hypothyroidism and agenesis 225040 AD?; AR?; XD?
of the corpus callosum
[5]
:
Xeroderma-talipes-enamel defects (XTE) [5] – AR
Dermoodontodysplasia 125640 AD
Odonto-onychodysplasia-alopecia [8] – AR
Brachymetapody-anodontia-hypotrichosis- 211370 AR
albinoidism
Monilethrix 158000 AD
Tricho-onychodysplasia-xeroderma [28] – AR
Pycnodysostosis 265800 AR
NOTE: The bold text highlights information not listed in an earlier article. [35]
AR: autosomal recessive; AD: autosomal dominant; ?: unknown; XD: X-linked dominant; XR:
:
X-linked recessive; ADULT: acro-dermato-ungual-lacrimal-tooth; GOMBO: growth
retardation, ocular abnormalities, microcephaly, brachydactyly, and oligophrenia.
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From: Pagnan NA, Visinon ÁF. Update on ectodermal dysplasias clinical classification. Am J Med Genet A 2014;
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Skin with fine, white, adherent scale is present in this patient with
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Multiple erosions and bullae are present on the foot of this child
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