TTD4
MCID: TRC101
MIFTS: 41

Trichothiodystrophy 4, Nonphotosensitive (TTD4)

Categories: Genetic diseases, Neuronal diseases, Reproductive diseases, Skin diseases

Aliases & Classifications for Trichothiodystrophy 4, Nonphotosensitive

MalaCards integrated aliases for Trichothiodystrophy 4, Nonphotosensitive:

Name: Trichothiodystrophy 4, Nonphotosensitive 57
Trichothiodystrophy, Nonphotosensitive 1 57 72 29 13 6
Amish Brittle Hair Brain Syndrome 57 12 72 70
Hair-Brain Syndrome 57 12 72
Bids Syndrome 57 12 72
Ttd4 57 12 72
Trichothiodystrophy-Neurocutaneous Syndrome 57 72
Nonphotosensitive Trichothiodystrophy 4 12 15
Trichorrhexis Nodosa Syndrome 72 70
Pollitt Syndrome 57 72
Ttdn1 57 72
Abhs 57 72
Trichothiodystrophy, Nonphotosensitive 1; Ttdn1 57
Trichothiodystrophy, Type 4, Nonphotosensitive 39
Trichothiodystrophy 4, Non-Photosensitive 72
Trichothiodystrophy Non-Photosensitive 1 72
Amish Brittle Hair Brain Syndrome; Abhs 57

Characteristics:

OMIM®:

57 (Updated 20-May-2021)
Inheritance:
autosomal recessive


HPO:

31
trichothiodystrophy 4, nonphotosensitive:
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Trichothiodystrophy 4, Nonphotosensitive

OMIM® : 57 Trichothiodystrophy is a rare autosomal recessive disorder in which patients have brittle, sulfur-deficient hair that displays a diagnostic alternating light and dark banding pattern, called 'tiger tail banding,' under polarizing microscopy. TTD patients display a wide variety of clinical features, including cutaneous, neurologic, and growth abnormalities. Common additional clinical features are ichthyosis, intellectual/developmental disabilities, decreased fertility, abnormal characteristics at birth, ocular abnormalities, short stature, and infections. There are both photosensitive and nonphotosensitive forms of the disorder (summary by Faghri et al., 2008). Sabinas brittle hair syndrome (211390) is another form of nonphotosensitive TTD. For a discussion of genetic heterogeneity of trichothiodystrophy, see 601675. (234050) (Updated 20-May-2021)

MalaCards based summary : Trichothiodystrophy 4, Nonphotosensitive, also known as trichothiodystrophy, nonphotosensitive 1, is related to trichothiodystrophy 1, photosensitive and trichothiodystrophy, and has symptoms including koilonychia An important gene associated with Trichothiodystrophy 4, Nonphotosensitive is MPLKIP (M-Phase Specific PLK1 Interacting Protein), and among its related pathways/superpathways is Ribosome biogenesis in eukaryotes. The drugs Ethanol and Lorazepam have been mentioned in the context of this disorder. Affiliated tissues include brain, eye and tongue, and related phenotypes are nystagmus and short nose

Disease Ontology : 12 A syndrome that is characterized by brittle hair, short stature, decreased fertility and cognitive impairment without photosensitivity has material basis in mutations in the TTDN1 gene.

UniProtKB/Swiss-Prot : 72 Trichothiodystrophy 4, non-photosensitive: A form of trichothiodystrophy, an autosomal recessive disease characterized by sulfur-deficient brittle hair and multisystem variable abnormalities. The spectrum of clinical features varies from mild disease with only hair involvement to severe disease with cutaneous, neurologic and profound developmental defects. Ichthyosis, intellectual and developmental disabilities, decreased fertility, abnormal characteristics at birth, ocular abnormalities, short stature, and infections are common manifestations. There are both photosensitive and non-photosensitive forms of the disorder. TTD4 patients do not manifest cutaneous photosensitivity.

Related Diseases for Trichothiodystrophy 4, Nonphotosensitive

Graphical network of the top 20 diseases related to Trichothiodystrophy 4, Nonphotosensitive:



Diseases related to Trichothiodystrophy 4, Nonphotosensitive

Symptoms & Phenotypes for Trichothiodystrophy 4, Nonphotosensitive

Human phenotypes related to Trichothiodystrophy 4, Nonphotosensitive:

31 (show all 28)
# Description HPO Frequency HPO Source Accession
1 nystagmus 31 occasional (7.5%) HP:0000639
2 short nose 31 occasional (7.5%) HP:0003196
3 anteverted nares 31 occasional (7.5%) HP:0000463
4 optic atrophy 31 occasional (7.5%) HP:0000648
5 retrognathia 31 occasional (7.5%) HP:0000278
6 epicanthus 31 occasional (7.5%) HP:0000286
7 cerebral cortical atrophy 31 occasional (7.5%) HP:0002120
8 microphthalmia 31 occasional (7.5%) HP:0000568
9 ventricular septal defect 31 occasional (7.5%) HP:0001629
10 microcornea 31 occasional (7.5%) HP:0000482
11 severe muscular hypotonia 31 occasional (7.5%) HP:0006829
12 partial agenesis of the corpus callosum 31 occasional (7.5%) HP:0001338
13 keratoconjunctivitis sicca 31 occasional (7.5%) HP:0001097
14 hypoplasia of teeth 31 occasional (7.5%) HP:0000685
15 intellectual disability 31 HP:0001249
16 global developmental delay 31 HP:0001263
17 macrotia 31 HP:0000400
18 microcephaly 31 HP:0000252
19 growth delay 31 HP:0001510
20 decreased fertility 31 HP:0000144
21 sparse hair 31 HP:0008070
22 woolly hair 31 HP:0002224
23 concave nail 31 HP:0001598
24 trichorrhexis nodosa 31 HP:0009886
25 psychomotor retardation 31 HP:0025356
26 sparse eyelashes 31 HP:0000653
27 small nail 31 HP:0001792
28 brittle hair 31 HP:0002299

Symptoms via clinical synopsis from OMIM®:

57 (Updated 20-May-2021)
Head And Neck Head:
microcephaly

Genitourinary Internal Genitalia Female:
decreased fertility

Neurologic Central Nervous System:
psychomotor retardation
hypotonia, severe (rare)
partial agenesis of the corpus callosum (rare)
cortical atrophy (rare)

Skin Nails Hair Nails:
hypoplastic nails
dysplastic nails
spoon-shaped nails
dyschromic nails

Head And Neck Ears:
large ears

Cardiovascular Heart:
ventricular septal defect (rare)

Head And Neck Nose:
short nose (rare)
large and depressed nasal root (rare)
thick alae (rare)
anteverted nares (rare)

Skeletal:
delayed ossification (rare)

Genitourinary Internal Genitalia Male:
decreased fertility

Skin Nails Hair Hair:
sparse hair
trichorrhexis nodosa
short, woolly hair
brittle hair of scalp, beard, eyebrows, eyelashes, and axillary and pubic areas
stubby eyebrow hair
more
Growth Other:
growth retardation

Head And Neck Teeth:
thin enamel
hypoplastic teeth (rare)

Head And Neck Eyes:
nystagmus (in some patients)
microcornea (in some patients)
microphthalmia (rare)
nystagmus (rare)
brittle and sparse eyebrows
more
Head And Neck Face:
short smooth philtrum (rare)
retrognathia, mild (rare)

Head And Neck Mouth:
white plaques on tongue

Skin Nails Hair Skin:
ichthyosiform areas of skin (rare)

Clinical features from OMIM®:

234050 (Updated 20-May-2021)

UMLS symptoms related to Trichothiodystrophy 4, Nonphotosensitive:


koilonychia

Drugs & Therapeutics for Trichothiodystrophy 4, Nonphotosensitive

Drugs for Trichothiodystrophy 4, Nonphotosensitive (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 28)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Ethanol Approved 64-17-5 702
2
Lorazepam Approved 846-49-1 3958
3
Dopamine Approved 51-61-6, 62-31-7 681
4
Diphenhydramine Approved, Investigational 147-24-0, 58-73-1 3100
5
Haloperidol Approved 52-86-8 3559
6
Histamine Approved, Investigational 51-45-6, 75614-87-8 774
7
Promethazine Approved, Investigational 60-87-7 4927
8 Pharmaceutical Solutions
9 Hand Sanitizers
10 Neurotransmitter Agents
11 Dopamine Agents
12 Hypnotics and Sedatives
13 Psychotropic Drugs
14 Gastrointestinal Agents
15 Antiemetics
16 Dopamine Antagonists
17 Haloperidol decanoate
18 Anesthetics
19 Anesthetics, Local
20 Anti-Anxiety Agents
21 GABA Modulators
22 Anti-Allergic Agents
23 Anticonvulsants
24 Antipsychotic Agents
25 Histamine Antagonists
26
Histamine Phosphate 51-74-1 65513
27 Dermatologic Agents
28 Histamine H1 Antagonists

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 "Alcohol Based Hand Sanitizers for the Prevention of Acute Diarrheal Disease and Acute Respiratory Infection in Children Under 5 Attending Childcare Centers in Bogotá, Cundinamarca and Tolima, in Colombia: a Cluster Randomized Control Trial" Completed NCT00963391
2 A Randomized Trial of the Effectiveness of Topical "ABH Gel" (Ativan®, Lorazepam; Benadryl®, Diphenhydramine; and Haldol®, Haloperidol Gel) Versus Placebo in Patients With Nausea Completed NCT01556932 ABH gel
3 Absorption of "ABH Gel" (Ativan®, Lorazepam; Benadryl®, Diphenhydramine; and Haldol®, Haloperidol Gel) From the Skin of Normal Volunteers Completed NCT01204255 lorazepam;diphenhydramine hydrochloride;haloperidol
4 Southwest Hub for American Indian Youth Suicide Prevention Research Recruiting NCT03543865
5 XatJove Anoia, as a Tool to Bring Health Services Closer to Teenagers Recruiting NCT04562350

Search NIH Clinical Center for Trichothiodystrophy 4, Nonphotosensitive

Genetic Tests for Trichothiodystrophy 4, Nonphotosensitive

Genetic tests related to Trichothiodystrophy 4, Nonphotosensitive:

# Genetic test Affiliating Genes
1 Trichothiodystrophy, Nonphotosensitive 1 29 MPLKIP

Anatomical Context for Trichothiodystrophy 4, Nonphotosensitive

MalaCards organs/tissues related to Trichothiodystrophy 4, Nonphotosensitive:

40
Brain, Eye, Tongue, Skin

Publications for Trichothiodystrophy 4, Nonphotosensitive

Articles related to Trichothiodystrophy 4, Nonphotosensitive:

(show all 18)
# Title Authors PMID Year
1
Pollitt syndrome patients carry mutation in TTDN1. 57 6
25606444 2014
2
Mutations in the C7orf11 (TTDN1) gene in six nonphotosensitive trichothiodystrophy patients: no obvious genotype-phenotype relationships. 6 57
16977596 2007
3
Identification of C7orf11 (TTDN1) gene mutations and genetic heterogeneity in nonphotosensitive trichothiodystrophy. 57 6
15645389 2005
4
Trichothiodystrophy: report of a new case with severe nervous system impairment. 57 6
1634754 1992
5
Trichothiodystrophy, mental retardation, short stature, ataxia, and gonadal dysfunction in three Moroccan siblings. 57 6
2333887 1990
6
"Brittle" hair with short stature, intellectual impairment and decreased fertility: an autosomal recessive syndrome in an Amish kindred. 57 6
4847854 1974
7
Sibs with mental and physical retardation and trichorrhexis nodosa with abnormal amino acid composition of the hair. 6 57
5645693 1968
8
Mitral regurgitation as a phenotypic manifestation of nonphotosensitive trichothiodystrophy due to a splice variant in MPLKIP. 6
26880286 2016
9
Ocular manifestations of trichothiodystrophy. 57
21959366 2011
10
Trichothiodystrophy: a systematic review of 112 published cases characterises a wide spectrum of clinical manifestations. 57
18603627 2008
11
Amish brittle hair syndrome gene maps to 7p14.1. 57
15723315 2005
12
Trichothiodystrophy, a transcription syndrome. 57
11335038 2001
13
Trichothiodystrophy without associated neuroectodermal defects. 57
9764166 1998
14
Trichothiodystrophy: an ultrastructural study of the hair follicle. 57
4063164 1985
15
Trichothiodystrophy: sulfur-deficient brittle hair as a marker for a neuroectodermal symptom complex. 57
7458366 1980
16
The physicochemical properties of hair in the BIDS syndrome. 57
984047 1976
17
Proteins of normal hair and of cystine-deficient hair from mentally retarded siblings. 57
5166328 1971
18
A homozygous G insertion in MPLKIP leads to TTDN1 with the hypergonadotropic hypogonadism symptom. 61
30598092 2018

Variations for Trichothiodystrophy 4, Nonphotosensitive

ClinVar genetic disease variations for Trichothiodystrophy 4, Nonphotosensitive:

6
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 MPLKIP NM_138701.4(MPLKIP):c.430A>G (p.Met144Val) SNV Pathogenic 1844 rs137853117 GRCh37: 7:40172768-40172768
GRCh38: 7:40133169-40133169
2 MPLKIP NM_138701.4(MPLKIP):c.137_138del (p.Gly46fs) Deletion Pathogenic 1845 rs587776531 GRCh37: 7:40174029-40174030
GRCh38: 7:40134430-40134431
3 MPLKIP MPLKIP, EX1-2DEL Deletion Pathogenic 1846 GRCh37:
GRCh38:
4 MPLKIP NM_138701.4(MPLKIP):c.277del (p.Ser93fs) Deletion Pathogenic 1847 rs587776532 GRCh37: 7:40173890-40173890
GRCh38: 7:40134291-40134291
5 MPLKIP NM_138701.4(MPLKIP):c.148_152del (p.His50fs) Deletion Pathogenic 1848 rs878854339 GRCh37: 7:40174015-40174019
GRCh38: 7:40134416-40134420
6 MPLKIP NM_138701.4(MPLKIP):c.339+1G>A SNV Pathogenic 224867 rs869312900 GRCh37: 7:40173827-40173827
GRCh38: 7:40134228-40134228
7 MPLKIP NM_138701.4(MPLKIP):c.2T>G (p.Met1Arg) SNV Pathogenic 1034262 GRCh37: 7:40174165-40174165
GRCh38: 7:40134566-40134566
8 MPLKIP NM_138701.4(MPLKIP):c.339+4ATA[2] Microsatellite Pathogenic 734604 rs377654804 GRCh37: 7:40173816-40173818
GRCh38: 7:40134217-40134219
9 MPLKIP NM_138701.4(MPLKIP):c.494G>T (p.Ser165Ile) SNV Uncertain significance 548559 rs778910338 GRCh37: 7:40172704-40172704
GRCh38: 7:40133105-40133105
10 MPLKIP NM_138701.4(MPLKIP):c.49G>A (p.Gly17Ser) SNV Uncertain significance 1031149 GRCh37: 7:40174118-40174118
GRCh38: 7:40134519-40134519

UniProtKB/Swiss-Prot genetic disease variations for Trichothiodystrophy 4, Nonphotosensitive:

72
# Symbol AA change Variation ID SNP ID
1 MPLKIP p.Met144Val VAR_022940 rs137853117

Expression for Trichothiodystrophy 4, Nonphotosensitive

Search GEO for disease gene expression data for Trichothiodystrophy 4, Nonphotosensitive.

Pathways for Trichothiodystrophy 4, Nonphotosensitive

Pathways related to Trichothiodystrophy 4, Nonphotosensitive according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1 10.66 SBDS EFL1

GO Terms for Trichothiodystrophy 4, Nonphotosensitive

Biological processes related to Trichothiodystrophy 4, Nonphotosensitive according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 ribosome biogenesis GO:0042254 8.96 SBDS EFL1
2 mature ribosome assembly GO:0042256 8.62 SBDS EFL1

Molecular functions related to Trichothiodystrophy 4, Nonphotosensitive according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 ribosome binding GO:0043022 8.62 SBDS EFL1

Sources for Trichothiodystrophy 4, Nonphotosensitive

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 20-May-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
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