Genodermatoses are inherited genetic skin conditions often grouped into three categories:

chromosomal, single gene, and polygenetic.[1]:547

A few genodermatoses

Epidermolysis Bullosa

Ichthyosis

Palmoplantar keratoderma

Neurofibromatosis

Xeroderma pigmentosum

Incontinentia pigmenti

Restrictive dermopathy

Epidermolysis bullosa
From Wikipedia, the free encyclopedia
(Redirected from Epidermolysis Bullosa)

Epidermolysis bullosa

A five-year-old boy with congenital

epidermolysis bullosa
Classification and external resources
Specialty
ICD-10
ICD-9-CM

Dermatology
Q81
757.39

DiseasesDB

31928 33248

MedlinePlus

001457

eMedicine

derm/124

Patient UK

Epidermolysis bullosa

MeSH

D004820
[edit on Wikidata]

Epidermolysis bullosa (EB) is a group of inherited connective tissue diseases that cause
blisters in the skin and mucosal membranes, with an incidence of 20 per million newborns in

the United States.[1] It is a result of a defect in anchoring between the epidermis and dermis,
resulting in friction and skin fragility. Its severity ranges from mild to lethal.
The condition was brought to public attention in 2004 in the UK through the Channel 4
documentary The Boy Whose Skin Fell Off, chronicling the life and death of Jonny Kennedy,
an Englishman with EB.[2] In the United States, the same could be said of the HBO
documentary My Flesh and Blood from 2003.[citation needed]
"Butterfly Children" is a term often used to describe younger patients (because the skin is
said to be as fragile as a butterflys wings),[3] "Cotton Wool Babies",[4][5] or (in South America)
as "Crystal Skin Children".[6]
Contents

1 Classification
o

1.1 Epidermolysis bullosa simplex

1.2 Junctional epidermolysis bullosa

1.3 Dystrophic epidermolysis bullosa

1.4 Other genetic

1.5 Other

2 Pathophysiology

3 Treatment

4 Epidemiology

5 Monitoring

6 See also

7 References

8 External links

Classification

Epidermolysis bullosa refers to a group of inherited disorders that involve the formation of
blisters following trivial trauma. Over 300 mutations have been identified in this condition.[7]
They have been classified into the following types:[8][9]:596
Epidermolysis bullosa simplex
Main article: Epidermolysis bullosa simplex

Epidermolysis bullosa simplex is a form of epidermolysis bullosa that causes blisters at the
site of rubbing. It typically affects the hands and feet, and is typically inherited in an
autosomal dominant manner, affecting the keratin genes KRT5 and KRT14.
Junctional epidermolysis bullosa
Main article: Junctional epidermolysis bullosa (medicine)

Junctional epidermolysis bullosa is an inherited disease affecting laminin and collagen. This
disease is characterised by blister formation within the lamina lucida of the basement
membrane zone[9]:599 and is inherited in an autosomal recessive manner. It also presents with
blisters at the site of friction, especially on the hands and feet, and has variants that can occur
in children and adults. Less than one per million people are estimated to have this form of
epidemolysis bullosa.[10]
Dystrophic epidermolysis bullosa
Main article: Dystrophic epidermolysis bullosa

Dystrophic epidermolysis bullosa is an inherited variant affecting the skin and other organs.
"Butterfly children" is the term given to those born with the disease, as their skin is seen to be
as delicate and fragile as a butterfly's wings. Dystrophic epidermolysis bullosa is caused by
genetic defects (or mutations) within the human COL7A1 gene encoding the protein type VII
collagen (collagen VII).[11] DEB-causing mutations can be either autosomal dominant or
autosomal recessive.
Other genetic
OMIM
609638

Name

epidermolysis bullosa, lethal acantholytic

Locus
6p24

Gene
DSP

Other

Epidermolysis bullosa acquisita

Epidermolysis bullosa pruriginosa

Pathophysiology

The human skin consists of two layers: an outermost layer called the epidermis and a layer
underneath called the dermis. In individuals with healthy skin, there are protein anchors
between these two layers that prevent them from moving independently from one another
(shearing). In people born with EB, the two skin layers lack the protein anchors that hold
them together, resulting in extremely fragile skineven minor mechanical friction (like
rubbing or pressure) or trauma will separate the layers of the skin and form blisters and
painful sores. Sufferers of EB have compared the sores with third-degree burns.[12]
Furthermore, as a complication of the chronic skin damage, people suffering from EB have
an increased risk of malignancies (cancers) of the skin.

Treatment

Treatment of the epidermolysis bullosa by transplantation of laminin5 modified

stem cells

Recent research has focused on changing the mixture of keratins produced in the skin. There
are 54 known keratin genesof which 28 belong to the type I intermediate filament genes
and 26 to type IIwhich work as heterodimers. Many of these genes share substantial
structural and functional similarity, but they are specialized to cell type and/or conditions
under which they are normally produced. If the balance of production could be shifted away
from the mutated, dysfunctional keratin gene toward an intact keratin gene, symptoms could
be reduced. For example, sulforaphane, a compound found in broccoli, was found to reduce
blistering in a mouse model to the point where affected pups could not be identified visually,
when injected into pregnant mice (5 mol/day = 0.9 mg) and applied topically to newborns (1
mol/day = 0.2 mg in jojoba oil).[13]
As of 2008 clinical research at the University of Minnesota has included a bone marrow
transplant to a 2-year-old child who is one of 2 brothers with EB. The procedure was
successful, strongly suggesting that a cure may have been found. A second transplant has also
been performed on the child's older brother, and a third transplant is scheduled for a
California baby. The clinical trial will ultimately include transplants to 30 subjects.[14]
However, the severe immunosuppression that bone marrow transplantation requires causes a
significant risk of serious infections in patients with large scale blisters and skin erosions.
Indeed, at least four patients have died in the course of either preparation for or institution of
bone marrow transplantation for epidermolysis bullosa, out of only a small group of patients
treated so far.
A pilot study performed in 2015 suggests that systemic granulocyte-colony stimulating factor
(G-CSF) may promote increased wound healing in patients with dystrophic epidermolysis
bullosa. In this study seven patients with dystrophic epidermolysis bullosa were treated daily
with subcutaneous G-CSF for six days and then re-evaluated on the seventh day. After six
days of treatment with G-CSF, the size of the open lesions were reduced by a median of
75.5% and the number of blisters and erosions on the patients were reduced by a median of
36.6%. There will need to be many more studies using G-CSF as a treatment in epidermolysis

bullosa, with a larger and more diverse patient population and a longer time frame, but this
pilot study is encouraging for this new potential treatment.[15]
Epidemiology

An estimated 50 per million live births are diagnosed with EB, and 9 per million people in the
general population have the condition. Of these cases, approximately 92% are epidermolysis
bullosa simplex (EBS), 5% are dystrophic epidermolysis bullosa (DEB), 1% are junctional
epidermolysis bullosa (JEB), and 2% are unclassified. Carrier frequency ranges from 1 in 333
for JEB, to 1 in 450 for DEB; the carrier frequency for EBS is presumed to be much higher
than JEB or DEB.[citation needed]
The disorder occurs in every racial and ethnic group and affects both sexes.[16][17]
Monitoring

The Epidermolysis Bullosa Activity and Scarring index (EBDASI) is a scoring system that
objectively quantifies the severity of epidermolysis bullosa. The EBDASI is a tool for
clinicians and patients to monitor the severity of the disease. It has also been designed to
evaluate the response to new therapies for the treatment of EB. The EBDASI was developed
and validated by Professor Dedee Murrell and her team of students and fellows at the St
George Hospital, University of New South Wales, in Sydney, Australia. It was presented at
the International Investigative Dermatology congress in Edinburgh in 2013 and a paper-based
version was published in the Journal of American Academy of Dermatology in 2014.[18]

Ichthyosis
From Wikipedia, the free encyclopedia

Ichthyosis

Ichthyosis is characterized by rough, scaly

skin.
Classification and external resources
Specialty
ICD-10

Dermatology
Q80

ICD-9-CM

757.1

DiseasesDB

6646

MeSH

D007057
[edit on Wikidata]

Ichthyosis (plural ichthyoses) is a heterogeneous family of at least 28,[1] generalized, mostly

genetic skin disorders.
All types of ichthyosis have dry, thickened, scaly or flaky skin.[1] In many types there is
cracked skin,[2] which is said to resemble the scales on a fish; the word ichthyosis comes from
the Ancient Greek (ichthys), meaning "fish."[3]

The severity of symptoms can vary enormously, from the mildest, most common, type such
as ichthyosis vulgaris which may be mistaken for normal dry skin up to life-threatening
conditions such as harlequin type ichthyosis. Ichtyosis vulgaris accounts for more than 95%
of cases.[4]
Contents

1 Types
o

1.1 Genetic simple ichthyoses

1.2 Genetic disease with ichthyosis

1.3 Non-genetic ichthyosis

2 Diagnosis

3 Treatments

4 Other animals

5 See also

6 References

7 External links

Types

There are many types of ichthyoses and an exact diagnosis may be difficult. Types of
ichthyoses are classified by their appearance and their genetic cause. Ichthyosis caused by the
same gene can vary considerably in severity and symptoms. Some ichthyoses do not appear
to fit exactly into any one type. Also different genes can produce ichthyoses with similar
symptoms. Of note, X-linked ichthyosis is associated with Kallmann syndrome (close to
KAL1 gene). The most common or well-known types are as follows:[5]
Genetic simple ichthyoses
Name

OMI
M

Gene

Protein

Ichthyosis vulgaris

1467
FLG
00

Filaggrin

X-linked ichthyosis

3081
STS
00

Steroid sulfatase

Congenital ichthyosiform
erythroderma, Nonbullous
(nbCIE)

2421 TGM1,
Transglutaminase 1
00
ALOXE3/ALOX12 Arachidonate
B
lipoxygenase 3

Arachidonate 12lipoxygenase, 12R type

Epidermolytic hyperkeratosis 1138
KRT1, KRT10
(bullous ichthyosis, bCIE)
00

Keratins

Harlequin-type ichthyosis

2425
ABCA12
00

ATP-binding cassette
transporter 12

Ichthyosis bullosa of Siemens

1468
KRT2
00

Keratin 2A

Ichthyosis hystrix, CurthMacklin type

1465
KRT1
90

Keratin 1

Hystrix-like ichthyosis with

deafness

6025
GJB2
40

Connexin-26 (Gap
junction beta-2)

Lamellar ichthyosis, type 1

2423
TGM1
00

Transglutaminase 1

Lamellar ichthyosis, type 2

6012
ABCA12
77

ATP-binding cassette
transporter 12

Lamellar ichthyosis, type 3

6047
CYP4F22
77

Cytochrome P450,
subfamily 4F, polypeptide
22

Lamellar ichthyosis, type 4

6139
LIPN
43

Lipase family, member N

Lamellar ichthyosis, type 5

6065
ALOXE3
45

Arachidonate
lipoxygenase 3

Autosomal Recessive
Congenital Ichthyosis[6]

6150
CERS3
23

ceramide synthase 3

Genetic disease with ichthyosis

OMI
Name
M

Gene

Protein

CHILD Syndrome

3080
NSHDL
50

NAD(P) dependent steroid

dehydrogenase-like

Conradi-Hnermann syndrome

3029
EBP
60

Emopamil binding protein

Ichthyosis follicularis with

alopecia and photophobia
syndrome

3082
MBTPS2
05

Membrane-bound
transcription factor
peptidase, site 2

Keratitis-ichthyosis-deafness

1482 GJB2

Connexin-26

syndrome

10

Netherton syndrome

2565
SPINK5
00

Serine peptidase inhibitor,

Kazal type 5

Neutral lipid storage disease

with ichthyosis

2756
ABHD5
30

1-acylglycerol-3-phosphate
O-acyltransferase

Adult Refsum disease

2665 PHYH
00
PEX7

Phytanoyl-CoA hydroxylase
Peroxin 7

Ichthyosis and male

hypogonadism

3082
00

Sjgren-Larsson syndrome

2702
ALDH3A2
00

Fatty acid dehydrogenase

Photosensitive
trichothiodystrophy (IBIDS
syndrome)

ERCC2,
6016
ERCC3,
75
GTF2H5

Transcription factor IIH

components

Gaucher Disease, type 2

2309
GBA
00

Glucocerebrosidase

Non-genetic ichthyosis

Ichthyosis acquisita

Diagnosis

A physician often can diagnose ichthyosis by looking at the skin. A family history is very
useful. In some cases, a skin biopsy is done to help to confirm the diagnosis. In some
instances, genetic testing may be helpful in making a diagnosis. Diabetes has not been
definitively linked to acquired ichthyosis or ichthyosis vulgaris; however, there are case
reports associating new onset ichthyosis with diabetes.[7]
Ichthyosis has been found to be more common in any Native American, Asian, Mongolian
group. As of now, there is no way to prevent ichthyosis.
Treatments

Treatments for ichthyosis often take the form of topical application of creams and emollient
oils, in an attempt to hydrate the skin. Creams containing lactic acid have been shown to
work exceptionally well in some cases.[citation needed] Application of Propylene Glycol has been
used as another treatment method. Retinoids are also used for some conditions.
Exposure to sunlight may improve[citation needed] or worsen the condition. In some cases, excess
dead skin sloughs off much better from wet tanned skin after bathing or a swim, although the
dry skin might be preferable to the damaging effects of sun exposure.

There can be ocular manifestations of ichthyosis, such as corneal and ocular surface diseases.
Vascularizing keratitis, which is more commonly found in congenital keratitis-ichythosisdeafness (KID), may worsen with isotretinoin therapy.

Palmoplantar keratoderma
From Wikipedia, the free encyclopedia

Palmoplantar keratoderma

A picture of a 40 y/o Caucasian female with

only the soles of the feet affected. The
amputation was prior to this admission
Classification and external resources
Specialty
ICD-10
ICD-9-CM
OMIM
DiseasesDB

dermatology
L85.1-L85.2, Q82.8
701.1, 757.39
144200 600962
32042

eMedicine

derm/589

MeSH

D007645
[edit on Wikidata]

Palmoplantar keratodermas are a heterogeneous group of disorders characterized by

abnormal thickening of the palms and soles.
Autosomal recessive and dominant, X-linked, and acquired forms have all been described.
[1]:505[2]:211[3]

Contents

1 Clinical patterns
o

1.1 Diffuse

1.2 Focal

1.3 Punctate

1.4 Ungrouped

2 Genetics

3 See also

4 References

Clinical patterns

Clinically, three distinct patterns of palmoplantar keratoderma may be identified: diffuse,

focal, and punctate.[1]:505
Diffuse

Diffuse palmoplantar keratoderma is a type of palmoplantar keratoderma that is characterized

by an even, thick, symmetric hyperkeratosis over the whole of the palm and sole, usually
evident at birth or in the first few months of life.[1]:505 Restated, diffuse palmoplantar
keratoderma is an autosomal dominant disorder in which hyperkeratosis is confined to the
palms and soles.[4] The two major types can have a similar clinical appearance:[4]

Diffuse epidermolytic palmoplantar keratoderma (also known as

"Palmoplantar keratoderma cum degeneratione granulosa Vrner,"
"Vrner's epidermolytic palmoplantar keratoderma", and "Vrner
keratoderma"[4]) is one of the most common patterns of palmoplantar
keratoderma, an autosomal dominant condition that presents within the
first few months of life, characterized by a well-demarcated, symmetric
thickening of palms and soles, often with a "dirty" snakeskin appearance
due to underlying epidermolysis.[1]:506

Diffuse nonepidermolytic palmoplantar keratoderma (also known as

"Diffuse orthohyperkeratotic keratoderma," "Hereditary palmoplantar
keratoderma," "Keratosis extremitatum progrediens," "Keratosis
palmoplantaris diffusa circumscripta," "Tylosis," "UnnaThost disease", and
"UnnaThost keratoderma"[4]) is inherited as an autosomal dominant
condition and is present from infancy, characterized by a well-demarcated,
symmetric, often "waxy" keratoderma involving the whole of the palms
and soles.[1]:5068[2]:213

Focal

Focal palmoplantar keratoderma, a type of palmoplantar keratoderma in which large, compact

masses of keratin develop at sites of recurrent friction, principally on the feet, although also
on the palms and other sites, a pattern of calluses that may be discoid (nummular) or linear.

Focal palmoplantar keratoderma with oral mucosal hyperkeratosis (also

known as "Focal epidermolytic palmoplantar keratoderma," [4] "Hereditary
painful callosities,"[4][5] "Hereditary painful callosity syndrome,"[1] "Keratosis
follicularis,"[1] "Keratosis palmoplantaris nummularis",[1] and "Nummular
epidermolytic palmoplantar keratoderma"[4]) is an autosomal dominant
keratoderma that represents a clinical overlap syndrome with
pachyonychia congenita type I but without the classic nail involvement.
[1]:510

Punctate

Punctate palmoplantar keratoderma is a form of palmoplantar keratoderma in which many

tiny "raindrop" keratoses involve the palmoplantar surface, skin lesions which may involve
the whole of the palmoplantar surface, or may be more restricted in their distribution.[1]:505[4]

Type 1: Keratosis punctata palmaris et plantaris (also known as

"Autosomal-dominant hereditary punctate keratoderma associated with
malignancy," "BuschkeFischerBrauer disease," "Davis Colley disease,"
"Keratoderma disseminatum palmaris et plantaris," "Keratosis papulosa,"
"Keratoderma punctatum," "Keratodermia punctata," "Keratoma
hereditarium dissipatum palmare et plantare," "Palmar and plantar seed
dermatoses," "Palmar keratoses," "Papulotranslucent acrokeratoderma,"
"Punctate keratoderma," "Punctate keratoses of the palms and soles," and
"Maculosa disseminata") is a skin condition, an autosomal dominant
palmoplantar keratoderma with variable penetrance, characterized
clinically by multiple, tiny, punctate keratoses over the entire
palmoplantar surfaces, beginning over the lateral edge of the digits.
[1]:509[2]:212213
It has been linked to 15q22-q24.[6]

Type 2: Spiny keratoderma (also known as "Porokeratosis punctata

palmaris et plantaris," "Punctate keratoderma," and "Punctate
porokeratosis of the palms and soles") is an autosomal dominant
keratoderma of late onset that develops in patients aged 12 to 50,
characterized by multiple tiny keratotic plugs, mimicking the spines on a
music box, involving the entire palmoplantar surfaces. [1]:509[4]

Type 3: Focal acral hyperkeratosis (also known as "Acrokeratoelastoidosis

lichenoides," and "Degenerative collagenous plaques of the hand") is a
late-onset keratoderma, inherited as an autosomal dominant condition,
characterized by oval or polygonal crateriform papules developing along
the border of the hands, feet, and wrists. [1]:509 It is considered similar to
Costa acrokeratoelastoidosis.[7]

Ungrouped

Palmoplantar keratoderma and spastic paraplegia (also known as

"CharcotMarieTooth disease with palmoplantar keratoderma and nail

dystrophy"[1]) is an autosomal dominant or x-linked dominant condition

that begins in early childhood with thick focal keratoderma over the soles
and, to a lesser extent, the palms.[1]:513

Palmoplantar keratoderma of Sybert (also known as "Greither

palmoplantar keratoderma,"[1] "Greither syndrome,"[4] "Keratosis
extremitatum hereditaria progrediens,"[1] "Keratosis palmoplantaris
transgrediens et progrediens"[1] "Sybert keratoderma,"[4] and
"Transgrediens and progrediens palmoplantar keratoderma" [4]) is an
extremely rare autosomal dominant[8] keratoderma (a skin condition
involving horn-like growths) with symmetric severe involvement of the
whole palmoplantar surface in a glove-and-stocking distribution. [1]:509 It was
characterized by Aloys Greither in 1952.[9][10][11] It was characterized by
Virginia Sybert in 1988.[12]

Striate palmoplantar keratoderma (also known as "Acral keratoderma,"[1]

"Brnauer-Fuhs-Siemens type of palmoplantar keratoderma," [1] "Focal nonepidermolytic palmoplantar keratoderma,"[4] "Keratosis palmoplantaris
varians,"[1] "Palmoplantar keratoderma areata,"[4] "Palmoplantar
keratoderma striata,"[4] "Wachter keratoderma,"[4]:778,785 and "Wachters
palmoplantar keratoderma"[1]) is a cutaneous condition, an autosomal
dominant keratoderma principally involving the soles with onset in infancy
or the first few years of life.[1]:509

Type 1: 148700: DSG1

Type 2: 612908: DSP

Type 3: 607654: KRT1

Carvajal syndrome (also known as "Striate palmoplantar keratoderma with

woolly hair and cardiomyopathy"[4] and "Striate palmoplantar keratoderma
with woolly hair and left ventricular dilated cardiomyopathy," [1]) is a
cutaneous condition inherited in an autosomal recessive fashion, and due
to a defect in desmoplakin.[4]:811 Striate palmoplantar keratoderma, woolly
hair, and left ventricular dilated cardiomyopathy has been described in
both autosomal dominant and autosomal recessive forms, but only the
recessive forms have a clear association with dilated cardiomyopathy. [1]:513
The skin disease presents as a striate palmoplantar keratoderma with
some nonvolar involvement, particularly at sites of pressure or abrasion.
[1]:513

Scleroatrophic syndrome of Huriez (also known as "Huriez syndrome,"

"Palmoplantar keratoderma with scleroatrophy," [4] "Palmoplantar
keratoderma with sclerodactyly," "Scleroatrophic and keratotic dermatosis
of the limbs," and "Sclerotylosis") is an autosomal dominant keratoderma
with sclerodactyly present at birth with a diffuse symmetric keratoderma
of the palms and soles.[1]:513[2]:576 An association with 4q23 has been
described.[13] It was characterized in 1968.[14]

Vohwinkel syndrome (also known as "Keratoderma hereditaria mutilans," [4]

"Keratoma hereditaria mutilans,"[4] "Mutilating keratoderma of Vohwinkel",
[2]:213
"Mutilating palmoplantar keratoderma"[4]) is a diffuse autosomal

dominant keratoderma with onset in early infancy characterized by a

honeycombed keratoderma involving the palmoplantar surfaces. [1]:512 Mild
to moderate sensorineural hearing loss is often associated. [1] It has been
associated with GJB2.[15] It was characterized in 1929.[16]

Olmsted syndrome (also known as "Mutilating palmoplantar keratoderma

with periorificial keratotic plaques," "Mutilating palmoplantar keratoderma
with periorificial plaques"[4] and "Polykeratosis of Touraine") is a
keratoderma of the palms and soles, with flexion deformity of the digits,
that begins in infancy.[1]:510[2]:214[4] Treatment with retinoids has been
described.[17] It has been associated with mutations in TRPV3. [18]

Aquagenic keratoderma, also known as acquired aquagenic palmoplantar

keratoderma,[4]:788transient reactive papulotranslucent acrokeratoderma,[4]
aquagenic syringeal acrokeratoderma,[4] and aquagenic wrinkling of the
palms,[2] is a skin condition characterized by the development of white
papules on the palms after water exposure.[2]:215 The condition causes
irritation of the palms when touching certain materials after being wet,
e.g., paper, cloth. An association with cystic fibrosis has been suggested.
[19]

Neurofibromatosis
From Wikipedia, the free encyclopedia

Neurofibromatosis

Back of an elderly woman with

neurofibromatosis
Classification and external resources
Specialty

Neurosurgery

ICD-10

Q85.0

ICD-9-CM

237.7

ICD-O

M9540/0

OMIM

162200 101000,162091

eMedicine

derm/287

Patient UK

Neurofibromatosis

MeSH

D017253
[edit on Wikidata]

Neurofibromatosis (NF) refers to several genetically inherited conditions that are clinically
and genetically different and carry a high possibility of tumor formation.[1] This disorder is
divided into Neurofibromatosis type 1, Neurofibromatosis type 2 and Schwannomatosis.[2]
Contents

1 Signs

2 Cause

3 Pathophysiology

4 Diagnosis

5 Treatment

6 Prognosis

7 Epidemiology

8 See also

9 References

10 Further reading

11 External links

Signs

Neurofibromatosis (NF1) in early life may cause learning and behavior problems, about 60%
of children who have NF1 have a mild form of difficulty in school.[3] In terms of signs the
individual might have are the following:[4][5]

Six or more light brown dermatological spots (caf-au-lait spots")

At least two neurofibromas

At least two growths on the eye's iris

Abnormal growth of the spine (scoliosis)

Cause

Neurofibromatosis is an autosomal dominant disorder, which means only one copy of the
affected gene is needed for the disorder to develop. Therefore, if only one parent has
neurofibromatosis, his or her children have a 50% chance of developing the condition as
well.The affected child could have mild NF1 even though inherited from a parent with a
severe form of the disorder.[6] The types of neurofibromatosis are:

Neurofibromatosis type I, in which the nerve tissue grows tumors

(neurofibromas) that may be benign and may cause serious damage by
compressing nerves and other tissues. [7]

Neurofibromatosis type II, in which bilateral acoustic neuromas (tumors of

the vestibulocochlear nerve or cranial nerve 8 (CN VIII) also known as
schwannoma) develop, often leading to hearing loss. [8]

Schwannomatosis, in which painful schwannomas develop on spinal and

peripheral nerves.[9]

Pathophysiology

The pathophysiology of neurofibromatosis (type 1) consists of the NF1 gene protein.[10] This
protein is a tumor suppressor and therefore serves as a signal regulator of cell proliferation
and differentiation. A dysfunction of neurofibromin can affect regulation, and cause
uncontrolled cell proliferation. Schwann cells in neurofibromas have a mutation in the NF1
alleles.[11]
Diagnosis

CT scan

The neurofibromatoses are considered as RASopathies and as members of the

neurocutaneous syndromes (phakomatoses).[12] Conditions which may be confused with NF-1
but which are not considered NF include, LEOPARD syndrome,[13] and Legius syndrome[14]
The diagnosis of neurofibromatosis is done via the following means:[15]

Radiograph

MRI or CT scan

EEG

Slit-lamp examination

Genetic testing

Histology

Treatment

Surgical removal of tumors is an option, however the risks involved should be assessed
first[16] With regard to OPG (optic pathway gliomas) the preferred treatment is chemotherapy,
However radiotherapy isn't recommended in children who present with this disorder.[17] It is

recommended that at an early age children diagnosed with NF1 have an examination each
year, this is a form of monitoring any potential growths or changes related to the disorder.[18]
Prognosis

In most cases, symptoms of NF1 are mild, and individuals live normal and productive lives.
In some cases, however, NF1 can be severely debilitating and may cause cosmetic and
psychological issues.[medical citation needed] The course of NF2 varies greatly among individuals. In
some cases of NF2, the damage to nearby vital structures, such as other cranial nerves and the
brain stem, can be life-threatening. Most individuals with schwannomatosis have significant
pain. In some extreme cases the pain will be severe and disabling.[5]
Epidemiology

NF1 occurs 1 in 3000 individuals, and is equal among men and women. Furthermore, it is
among the most common inherited nervous system disorders.[19] Such individuals have a 10 to
15 year reduction in life expectancy compared to the average person.[20]
See also

Incontinentia pigmenti
From Wikipedia, the free encyclopedia
The lead section of this article may need to be rewritten. Please
discuss this issue on the article's talk page. Use the lead layout guide to
ensure the section will be inclusive of all essential details. (August 2010)

Incontinentia pigmenti
Classification and external resources
Specialty medical genetics
ICD-10

Q82.3

ICD-9-CM 757.33
OMIM

308300

DiseasesDB 29600
MedlinePlu
001583
s
eMedicine article/1114205 article/1176285
MeSH
GeneRevie
ws

D007184

Incontinentia pigmenti

[edit on Wikidata]

Incontinentia pigmenti (IP, also known as "BlochSiemens syndrome,"[1] "BlochSulzberger

disease,"[2] "BlochSulzberger syndrome"[1] "melanoblastosis cutis," and "nevus pigmentosus
systematicus") is a genetic disorder that affects the skin, hair, teeth, nails, and central nervous
system. It is named due to its microscopic appearance.
Contents

1 Presentation

2 Diagnosis

3 Genetics

4 History

5 See also

6 References

7 External links

Presentation

Incontinentia pigmenti forming along Blaschko's lines in a 3-year-old girl.

The skin lesions evolve through characteristic stages:

1. blistering (from birth to about four months of age),
2. a wart-like rash (for several months),
3. swirling macular hyperpigmentation (from about six months of age into
adulthood), followed by
4. linear hypopigmentation.

Alopecia, hypodontia, abnormal tooth shape, and dystrophic nails are observed. Some
patients have retinal vascular abnormalities predisposing to retinal detachment in early
childhood. Cognitive delays/mental retardation are occasionally seen.
Discolored skin is caused by excessive deposits of melanin (normal skin pigment). Most
newborns with IP will develop discolored skin within the first two weeks. The pigmentation
involves the trunk and extremities, is slate-grey, blue or brown, and is distributed in irregular
marbled or wavy lines. The discoloration sometimes fades with age.
Neurological problems can include: cerebral atrophy, the formation of small cavities in the
central white matter of the brain, and the loss of neurons in the cerebellar cortex. About 20%
of children with IP will have slow motor development, muscle weakness in one or both sides
of the body, mental retardation, and seizures. They are also likely to have visual problems,
which can include: crossed eyes, cataracts, and severe visual loss. Dental problems are
common, and include missing or peg-shaped teeth - patients with IP often keep milk teeth
into adult life.
Breast anomalies can occur in 1% of patients; anomalies can include hypoplasia and
supernumerary nipples.
Skeletal and structural anomalies can occur in approximately 14% of patients, including:

Somatic asymmetry,

Hemivertebrae,

Scoliosis,

Spina bifida,

Syndactyly,

Acheiria (congenital absence of the hands - note: other limbs may be

affected),

Ear anomalies,

Extra ribs,

Skull deformities,

Primary pulmonary hypertension,

Cardiopulmonary failure

Diagnosis

The diagnosis of IP is established by clinical findings and occasionally by corroborative skin

biopsy. Molecular genetic testing of the NEMO IKBKG gene (chromosomal locus Xq28)
reveals disease-causing mutations in about 80% of probands. Such testing is available
clinically.
In addition, females with IP have skewed X-chromosome inactivation; testing for this can be
used to support the diagnosis.
Many people in the past were misdiagnosed with a second type of IP, formerly known as IP1.
This has now been given its own name - 'Hypomelanosis of Ito' (incontinentia pigmenti
achromians). This has a slightly different presentation: swirls or streaks of hypopigmentation
and depigmentation. It is not inherited and does not involve skin stages 1 or 2. Some 3350%
of patients have multisystem involvement eye, skeletal, and neurological abnormalities. Its
chromosomal locus is at Xp11, rather than Xq28.
Genetics

IP is inherited in an X-linked dominant manner.[3][4] IP is lethal in most, but not all, males. A
female with IP may have inherited the IKBKG mutation from either parent or have a new
gene mutation. Parents may either be clinically affected or have germline mosaicism.
Affected women have a 50% risk of transmitting the mutant IKBKG allele at conception;
however, most affected male conceptuses miscarry. Thus, the expected ratio for liveborn
children is 33% unaffected females, 33% affected females, and 33% unaffected males.
Genetic counseling, prenatal testing, and preimplantation genetic diagnosis is available.
In females, the cells expressing the mutated IKBKG gene due to lyonization selectively die
around the time of birth so the X-inactivation is extremely skewed.[5]
IP is caused by mutations in a gene called NEMO (NF-kappaB essential modulator).

Restrictive dermopathy
From Wikipedia, the free encyclopedia

Restrictive dermopathy
Classification and external resources
Specialty

medical genetics

ICD-10

Q82.8

OMIM

275210

DiseasesDB

32974
[edit on Wikidata]

Restrictive dermopathy is a rare, lethal autosomal recessive skin condition characterized by

abnormal facies, tight skin, sparse or absent eyelashes, and secondary joint changes.[1]:563
Mechanism

Restrictive dermopathy (RD) is caused either by the loss of the gene ZMPSTE24, which
encodes a protein responsible for the cleavage of farnesylated prelamin A (progerin) into
mature non-farnesylated lamin, or by a mutation in the LMNA gene. This results in the
accumulation of farnesyl-prelamin A at the nuclear membrane.[2] Mechanistically, restrictive
dermopathy is somewhat similar to Hutchinson-Gilford progeria syndrome (HGPS), a disease
where the last step in lamin processing is hindered by a mutation that causes the loss of the
ZMPSTE24 cleavage site in the lamin A gene.
See also

Relapsing linear acantholytic dermatosis

List of cutaneous conditions

Lamellar ichthyosis - Possible differential diagnosis

References
1.

James, William; Berger, Timothy; Elston, Dirk (2005). Andrews'

Diseases of the Skin: Clinical Dermatology. (10th ed.). Saunders. ISBN 07216-2921-0.

2.

Young SG, Meta M, Yang SH, Fong LG (December 2006). "Prelamin A

farnesylation and progeroid syndromes". J. Biol. Chem. 281 (52): 39741
39745. doi:10.1074/jbc.R600033200. PMID 17090536.