MCID: ICH011
MIFTS: 26

Ichthyosis Follicularis Atrichia Photophobia Syndrome

Categories: Cardiovascular diseases, Ear diseases, Eye diseases, Rare diseases

Aliases & Classifications for Ichthyosis Follicularis Atrichia Photophobia Syndrome

MalaCards integrated aliases for Ichthyosis Follicularis Atrichia Photophobia Syndrome:

Name: Ichthyosis Follicularis Atrichia Photophobia Syndrome 20 6 71
Syndrome, Ifap 39
Ifap Syndrome 20

Classifications:



External Ids:

UMLS 71 C1839988

Summaries for Ichthyosis Follicularis Atrichia Photophobia Syndrome

GARD : 20 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.Orpha Number: 2273DefinitionIchthyosis follicularis - alopecia - photophobia (IFAP) is a rare genetic disorder characterized by the triad of ichthyosis follicularis, alopecia, and photophobia from birth.EpidemiologyPrevalence is unknown. Approximately 40 cases have been reported to date. IFAP primarily affects male subjects. Female carriers may develop some clinical features.Clinical descriptionAll patients present with congenital follicular ichthyosis, alopecia involving the scalp, eyebrows and eyelashes, and photophobia (in the first year of life, infancy or early childhood). Ichthyosis follicularis is characterized by widespread non-inflammatory thorn-like follicular projections. Hyperkeratotic papules are most pronounced over the extensor extremities and scalp and are distributed symmetrically. Non-cicatricial complete body alopecia is also a classical feature. Variable degrees of a collodion membrane may be present in newborns. Psoriasiform plaques, angular cheilitis, periungueal inflammation, dystrophic nails, hypohidrosis and atopic eczema can be present. The palms and soles are generally unaffected. Superficial corneal ulceration and vascularization may lead to progressive corneal scarring. Male patients have relentless progression of corneal vascularization and loss of vision. Atopic keratoconjunctival inflammation, chronic tearing, cataract, horizontal nystagmus, astigmatism and myopia have been reported. In a few cases, mild to severe intellectual disability, short stature, microcephaly, seizures, dysmorphic features (frontal bossing, choanal atresia, large ears), cleft hands, intestinal anomalies (omphalocele, Hirschsprung disease or congenital aganglionic megacolon (see these terms), small intestine stenosis, inguinal hernia), as well as renal, cardiac and vertebral anomalies can be present. Recurrent infections are common. External genitalia are generally normal with a few cases of cryptorchidism and one with hypospadias. Affected or carrier females may have milder symptoms (cutaneous hyperkeratotic lesions that follow the lines of Blaschko, asymmetric distribution of body hair, patchy alopecia).EtiologyThe disorder is caused by mutations in the MBTPS2 gene (Xp22.12-p22.11) leading to impaired cholesterol homeostasis and response to endoplasmic reticulum stress.Diagnostic methodsDiagnosis is based on the clinical features and on testing of the MBTPS2 gene.Differential diagnosisDifferential diagnosis includes dermotrichic syndrome, hereditary mucoepithelial dysplasia, keratitis-ichthyosis-deafness (KID syndrome) and keratosis follicularis spinulosa decalvans (see these terms).Antenatal diagnosisIFAP cannot be detected prenatally by ultrasound.Genetic counselingIf the mutation has been identified in a carrier mother, prenatal diagnosis can be proposed. Transmission is X-linked recessive. The mutation might also arise de novo. A few cases of autosomal dominant inheritance have been reported.Management and treatmentFollicular hyperkeratosis can be treated using topical keratolytics, emollients and urea preparations. A moderate response to acitretin therapy has been found in some patients. Intensive lubrication of the ocular surface is essential. Corneal vascularization does not respond to topical corticosteroids.PrognosisPrognosis is variable. Some patients die in the neonatal period while others have normal life expectancy. However, in most patients, progressive loss of vision leads to loss of autonomy. Cardiopulmonary complications are the main cause of death.Visit the Orphanet disease page for more resources.

MalaCards based summary : Ichthyosis Follicularis Atrichia Photophobia Syndrome, also known as syndrome, ifap, is related to ifap syndrome 1, with or without bresheck syndrome and ichthyosis, and has symptoms including seizures and photophobia. An important gene associated with Ichthyosis Follicularis Atrichia Photophobia Syndrome is GJB2 (Gap Junction Protein Beta 2), and among its related pathways/superpathways are Chks in Checkpoint Regulation and Regulation of cholesterol biosynthesis by SREBP (SREBF). Affiliated tissues include small intestine.

Related Diseases for Ichthyosis Follicularis Atrichia Photophobia Syndrome

Diseases related to Ichthyosis Follicularis Atrichia Photophobia Syndrome via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 44)
# Related Disease Score Top Affiliating Genes
1 ifap syndrome 1, with or without bresheck syndrome 31.6 SREBF1 MBTPS2 GJB2
2 ichthyosis 30.3 MBTPS2 GJB2
3 keratosis 29.5 MBTPS2 GJB2
4 ifap syndrome 2 11.4
5 alopecia 10.5
6 inguinal hernia 10.2
7 ichthyosis, follicular 10.2
8 keratitis, hereditary 10.1
9 erythrokeratoderma ''en cocardes'' 10.1
10 seizure disorder 10.1
11 cryptorchidism, unilateral or bilateral 10.0
12 alopecia, congenital 10.0
13 olmsted syndrome, x-linked 10.0
14 branchiootic syndrome 1 10.0
15 palmoplantar keratosis 10.0
16 rare genetic skin disease 10.0
17 cleft palate, isolated 9.9
18 darier-white disease 9.9
19 hirschsprung disease 1 9.9
20 mucoepithelial dysplasia, hereditary 9.9
21 nail disorder, nonsyndromic congenital, 1 9.9
22 alopecia universalis congenita 9.9
23 lymphoma, hodgkin, classic 9.9
24 dermatitis, atopic 9.9
25 keratosis follicularis spinulosa decalvans, autosomal dominant 9.9
26 olmsted syndrome 1 9.9
27 alacrima, achalasia, and mental retardation syndrome 9.9
28 chorea, childhood-onset, with psychomotor retardation 9.9
29 lymphoma 9.9
30 umbilical hernia 9.9
31 keratosis follicularis spinulosa decalvans 9.9
32 mutilating palmoplantar keratoderma with periorificial keratotic plaques 9.9
33 rickets 9.9
34 megacolon 9.9
35 myopia 9.9
36 choreatic disease 9.9
37 candidiasis 9.9
38 ectodermal dysplasia 9.9
39 keratopathy 9.9
40 retinal vascular disease 9.9
41 dermatitis 9.9
42 skin atrophy 9.9
43 hypotrichosis 9.9
44 dermotrichic syndrome 9.9

Graphical network of the top 20 diseases related to Ichthyosis Follicularis Atrichia Photophobia Syndrome:



Diseases related to Ichthyosis Follicularis Atrichia Photophobia Syndrome

Symptoms & Phenotypes for Ichthyosis Follicularis Atrichia Photophobia Syndrome

UMLS symptoms related to Ichthyosis Follicularis Atrichia Photophobia Syndrome:


seizures, photophobia

Drugs & Therapeutics for Ichthyosis Follicularis Atrichia Photophobia Syndrome

Search Clinical Trials , NIH Clinical Center for Ichthyosis Follicularis Atrichia Photophobia Syndrome

Genetic Tests for Ichthyosis Follicularis Atrichia Photophobia Syndrome

Anatomical Context for Ichthyosis Follicularis Atrichia Photophobia Syndrome

MalaCards organs/tissues related to Ichthyosis Follicularis Atrichia Photophobia Syndrome:

40
Small Intestine

Publications for Ichthyosis Follicularis Atrichia Photophobia Syndrome

Articles related to Ichthyosis Follicularis Atrichia Photophobia Syndrome:

(show all 11)
# Title Authors PMID Year
1
Atrichia, ichthyosis, follicular hyperkeratosis, chronic candidiasis, keratitis, seizures, mental retardation and inguinal hernia: a severe manifestation of IFAP syndrome? 61 6
10694306 2000
2
Recurrent splice-site mutation in MBTPS2 underlying IFAP syndrome with Olmsted syndrome-like features in a Chinese patient. 6
24313295 2014
3
MBTPS2 mutation causes BRESEK/BRESHECK syndrome. 6
22105905 2012
4
Intronic mutations affecting splicing of MBTPS2 cause ichthyosis follicularis, alopecia and photophobia (IFAP) syndrome. 6
21426410 2011
5
IFAP syndrome is caused by deficiency in MBTPS2, an intramembrane zinc metalloprotease essential for cholesterol homeostasis and ER stress response. 6
19361614 2009
6
Updated strategies for the management, pathogenesis and molecular genetics of different forms of ichthyosis syndromes with prominent hair abnormalities. 61
28913623 2017
7
Ichthyosis follicularis with alopecia and photophobia syndrome (IFAP): A Case Report. 61
28329493 2017
8
Clinical and molecular characterization of two patients with palmoplantar keratoderma-congenital alopecia syndrome type 2. 61
27339777 2016
9
Expanding the phenotype of IFAP/BRESECK syndrome: a new case with severe hypogammaglobulinemia. 61
24090718 2013
10
Ichthyosis follicularis, alopecia and photophobia syndrome (IFAP): report of the first case with ocular and cutaneous manifestations in Brazil with a favorable response to treatment. 61
21670910 2011
11
Plasminogen activator inhibitor-2 is expressed in different types of congenital ichthyosis: in vivo evidence for its cross-linking into the cornified cell envelope by transglutaminase-1. 61
16634887 2006

Variations for Ichthyosis Follicularis Atrichia Photophobia Syndrome

ClinVar genetic disease variations for Ichthyosis Follicularis Atrichia Photophobia Syndrome:

6 (show all 13)
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 MBTPS2 NM_015884.4(MBTPS2):c.680A>T (p.His227Leu) SNV Pathogenic 11402 rs122468176 X:21886594-21886594 X:21868476-21868476
2 MBTPS2 NM_015884.4(MBTPS2):c.261G>A (p.Met87Ile) SNV Pathogenic 11403 rs122468177 X:21863325-21863325 X:21845207-21845207
3 MBTPS2 NM_015884.4(MBTPS2):c.1424T>C (p.Phe475Ser) SNV Pathogenic 11405 rs122468179 X:21900637-21900637 X:21882519-21882519
4 MBTPS2 NM_015884.4(MBTPS2):c.677G>T (p.Trp226Leu) SNV Pathogenic 11406 rs122468180 X:21886591-21886591 X:21868473-21868473
5 MBTPS2 NM_015884.4(MBTPS2):c.671-9T>G SNV Pathogenic 126904 rs587777305 X:21886576-21886576 X:21868458-21868458
6 GJB2 NM_004004.6(GJB2):c.526A>G (p.Asn176Asp) SNV Pathogenic 590275 rs781767722 13:20763195-20763195 13:20189056-20189056
7 SREBF1 NM_001005291.3(SREBF1):c.1669C>T (p.Arg557Cys) SNV Pathogenic 932243 17:17720597-17720597 17:17817283-17817283
8 SREBF1 NM_001005291.3(SREBF1):c.1672_1674del (p.Asn558del) Deletion Pathogenic 932244 17:17720592-17720594 17:17817278-17817280
9 SREBF1 NM_001005291.3(SREBF1):c.1679T>C (p.Leu560Pro) SNV Pathogenic 932245 17:17720587-17720587 17:17817273-17817273
10 MBTPS2 NM_015884.4(MBTPS2):c.1286G>A (p.Arg429His) SNV Pathogenic 11404 rs122468178 X:21899039-21899039 X:21880921-21880921
11 MBTPS2 NM_015884.4(MBTPS2):c.529A>C (p.Ile177Leu) SNV Uncertain significance 522925 rs766760741 X:21869717-21869717 X:21851599-21851599
12 MBTPS2 NM_015884.4(MBTPS2):c.119A>C (p.Asn40Thr) SNV Uncertain significance 931186 X:21861331-21861331 X:21843213-21843213
13 MBTPS2 NM_015884.4(MBTPS2):c.1520C>T (p.Ala507Val) SNV Uncertain significance 931207 X:21900733-21900733 X:21882615-21882615

Expression for Ichthyosis Follicularis Atrichia Photophobia Syndrome

Search GEO for disease gene expression data for Ichthyosis Follicularis Atrichia Photophobia Syndrome.

Pathways for Ichthyosis Follicularis Atrichia Photophobia Syndrome

Pathways related to Ichthyosis Follicularis Atrichia Photophobia Syndrome according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
11.76 SREBF1 MBTPS2
2
Show member pathways
10.94 SREBF1 MBTPS2
3 10.49 SREBF1 MBTPS2

GO Terms for Ichthyosis Follicularis Atrichia Photophobia Syndrome

Biological processes related to Ichthyosis Follicularis Atrichia Photophobia Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 lipid metabolic process GO:0006629 9.4 SREBF1 MBTPS2
2 aging GO:0007568 9.37 SREBF1 GJB2
3 steroid metabolic process GO:0008202 9.32 SREBF1 MBTPS2
4 cholesterol metabolic process GO:0008203 9.26 SREBF1 MBTPS2
5 response to retinoic acid GO:0032526 9.16 SREBF1 GJB2
6 response to progesterone GO:0032570 8.96 SREBF1 GJB2
7 regulation of cholesterol biosynthetic process GO:0045540 8.62 SREBF1 MBTPS2

Sources for Ichthyosis Follicularis Atrichia Photophobia Syndrome

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
20 GARD
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 05-Mar-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
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