SADDAN
MCID: ACH043
MIFTS: 49

Achondroplasia, Severe, with Developmental Delay and Acanthosis Nigricans (SADDAN)

Categories: Bone diseases, Fetal diseases, Genetic diseases, Neuronal diseases, Rare diseases, Skin diseases

Aliases & Classifications for Achondroplasia, Severe, with Developmental Delay and Acanthosis...

MalaCards integrated aliases for Achondroplasia, Severe, with Developmental Delay and Acanthosis Nigricans:

Name: Achondroplasia, Severe, with Developmental Delay and Acanthosis Nigricans 57 25 75 73
Saddan 57 12 76 25 59 75 37 15 40
Saddan Dysplasia 57 12 53 25 75
Severe Achondroplasia with Developmental Delay and Acanthosis Nigricans 12 53 25 29
Ssb Syndrome 53 25
Severe Achondroplasia-Developmental Delay-Acanthosis Nigricans Syndrome 59
Skeleton Skin Brain Syndrome 53
Skeleton-Skin-Brain Syndrome 25
Achondroplasia 44

Characteristics:

Orphanet epidemiological data:

59
severe achondroplasia-developmental delay-acanthosis nigricans syndrome
Inheritance: Autosomal dominant,Not applicable; Prevalence: <1/1000000 (Worldwide); Age of onset: Childhood;

OMIM:

57
Inheritance:
autosomal dominant

Miscellaneous:
clinical overlap with thanatophoric dysplasia i and severe achondroplasia


HPO:

32
achondroplasia, severe, with developmental delay and acanthosis nigricans:
Inheritance autosomal dominant inheritance


Classifications:



Summaries for Achondroplasia, Severe, with Developmental Delay and Acanthosis...

UniProtKB/Swiss-Prot : 75 Achondroplasia, severe, with developmental delay and acanthosis nigricans: A severe form of achondroplasia associated with developmental delay and acanthosis nigricans. Patients manifest short-limb dwarfism, with a long, narrow trunk, short extremities, particularly in the proximal (rhizomelic) segments, a large head with frontal bossing, hypoplasia of the midface and a trident configuration of the hands. Acanthosis nigricans is a skin condition characterized by brown-pigmented, velvety verrucosities in body folds and creases.

MalaCards based summary : Achondroplasia, Severe, with Developmental Delay and Acanthosis Nigricans, also known as saddan, is related to thanatophoric dysplasia, type i and thanatophoric dysplasia, type ii, and has symptoms including seizures An important gene associated with Achondroplasia, Severe, with Developmental Delay and Acanthosis Nigricans is FGFR3 (Fibroblast Growth Factor Receptor 3), and among its related pathways/superpathways are MAPK signaling pathway and Ras signaling pathway. Affiliated tissues include skin, brain and bone, and related phenotypes are brain atrophy and microcephaly

Disease Ontology : 12 An autosomal dominant disease characterized by severe achondroplasia, developmental delay and acanthosis nigricans that has material basis in heterozygous mutation in the FGFR3 gene on chromosome 4p16.

Genetics Home Reference : 25 SADDAN (severe achondroplasia with developmental delay and acanthosis nigricans) is a rare disorder of bone growth characterized by skeletal, brain, and skin abnormalities.

Wikipedia : 76 Severe achondroplasia with developmental delay and acanthosis nigricans (SADDAN), is a very rare genetic... more...

Description from OMIM: 616482

Related Diseases for Achondroplasia, Severe, with Developmental Delay and Acanthosis...

Diseases related to Achondroplasia, Severe, with Developmental Delay and Acanthosis Nigricans via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 102)
# Related Disease Score Top Affiliating Genes
1 thanatophoric dysplasia, type i 30.5 FGFR3 STAT1
2 thanatophoric dysplasia, type ii 29.5 FGFR3 STAT1
3 achondroplasia 13.0
4 achondroplasia and severe combined immunodeficiency 12.3
5 achondroplasia and swiss type agammaglobulinemia 12.1
6 hypochondroplasia 11.9
7 dwarfism 11.6
8 short-limb skeletal dysplasia with severe combined immunodeficiency 11.4
9 pseudoachondroplasia 11.4
10 atelosteogenesis, type i 11.0
11 boomerang dysplasia 11.0
12 hydrocephalus, congenital, 1 11.0
13 mesomelia 11.0
14 hydrocephalus 10.3
15 spinal stenosis 10.3
16 sleep apnea 10.3
17 acanthosis nigricans 10.2
18 down syndrome 10.1
19 spondyloepiphyseal dysplasia with congenital joint dislocations 10.1
20 spondyloepiphyseal dysplasia congenita 10.1
21 pulmonary hypertension 10.1
22 craniosynostosis 10.1
23 skeletal dysplasias 10.1
24 brittle bone disorder 10.0
25 body mass index quantitative trait locus 1 10.0
26 rickets 10.0
27 synostosis 10.0
28 osteochondrodysplasia 10.0
29 crouzon syndrome 9.9
30 crouzon syndrome with acanthosis nigricans 9.9
31 osteoarthritis 9.9
32 achondrogenesis 9.9
33 lipomatosis 9.9
34 pelvic lipomatosis 9.9
35 megalencephaly 9.9
36 mouth disease 9.8 JAK1 STAT1
37 pfeiffer syndrome 9.8
38 spondyloarthropathy 1 9.8
39 coxa vara 9.8
40 leri-weill dyschondrosteosis 9.8
41 fundus albipunctatus 9.8
42 marfan syndrome 9.8
43 nail-patella syndrome 9.8
44 neurofibromatosis, type i 9.8
45 pelvic organ prolapse 9.8
46 teeth, supernumerary 9.8
47 tetralogy of fallot 9.8
48 trigeminal neuralgia 9.8
49 renal hypodysplasia/aplasia 1 9.8
50 diastrophic dysplasia 9.8

Graphical network of the top 20 diseases related to Achondroplasia, Severe, with Developmental Delay and Acanthosis Nigricans:



Diseases related to Achondroplasia, Severe, with Developmental Delay and Acanthosis Nigricans

Symptoms & Phenotypes for Achondroplasia, Severe, with Developmental Delay and Acanthosis...

Symptoms via clinical synopsis from OMIM:

57
Head And Neck Face:
frontal bossing
midface hypoplasia

Head And Neck Head:
megalencephaly
large anterior fontanel

Respiratory:
sleep apnea
respiratory compromise at birth

Skin Nails Hair Skin:
acanthosis nigricans
redundant skin folds on upper and lower limbs

Head And Neck Ears:
otitis media
hearing loss, mild-to-moderate

Head And Neck Eyes:
exotropia (in some patients)
high myopia (in some patients)

Cardiovascular Vascular:
pulmonary hypertension (in some patients)

Chest External Features:
small chest with flaring costal margins

Skeletal Pelvis:
posterior rotation of hips

Neurologic Central Nervous System:
hydrocephalus
seizures
central apnea
developmental delay
thin corpus callosum
more
Skeletal Spine:
kyphosis
platyspondyly
lumbar lordosis
cervical spinal stenosis

Head And Neck Nose:
depressed nasal bridge

Skeletal Limbs:
rhizomelia
mesomelia
anterior bowing of femora
posterior bowing of tibiae

Growth Height:
dwarfism
short stature, severe disproportionate

Abdomen Gastrointestinal:
gastroesophageal reflux (in some patients)

Cardiovascular Heart:
congestive heart failure (in some patients)

Skeletal Skull:
overgrowth of mandible in adults
pneumatization of the sinuses


Clinical features from OMIM:

616482

Human phenotypes related to Achondroplasia, Severe, with Developmental Delay and Acanthosis Nigricans:

59 32 (show all 40)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 brain atrophy 59 32 hallmark (90%) Very frequent (99-80%) HP:0012444
2 microcephaly 59 32 frequent (33%) Frequent (79-30%) HP:0000252
3 intellectual disability, severe 59 32 hallmark (90%) Very frequent (99-80%) HP:0010864
4 acanthosis nigricans 59 32 hallmark (90%) Very frequent (99-80%) HP:0000956
5 severe global developmental delay 59 32 hallmark (90%) Very frequent (99-80%) HP:0011344
6 aplasia/hypoplasia of the mandible 59 32 hallmark (90%) Very frequent (99-80%) HP:0009118
7 metaphyseal chondrodysplasia 59 32 hallmark (90%) Very frequent (99-80%) HP:0005871
8 abnormality of the clavicle 59 32 frequent (33%) Frequent (79-30%) HP:0000889
9 hypoplasia of the corpus callosum 59 32 hallmark (90%) Very frequent (99-80%) HP:0002079
10 femoral bowing 59 32 frequent (33%) Frequent (79-30%) HP:0002980
11 tibial bowing 59 32 frequent (33%) Frequent (79-30%) HP:0002982
12 fibular bowing 59 32 frequent (33%) Frequent (79-30%) HP:0010502
13 enlarged cerebellum 59 32 hallmark (90%) Very frequent (99-80%) HP:0012081
14 frontal bossing 32 HP:0002007
15 hydrocephalus 32 HP:0000238
16 intellectual disability 32 HP:0001249
17 seizures 32 HP:0001250
18 megalencephaly 32 HP:0001355
19 kyphosis 32 HP:0002808
20 sleep apnea 32 HP:0010535
21 hearing impairment 32 HP:0000365
22 global developmental delay 32 HP:0001263
23 depressed nasal bridge 32 HP:0005280
24 gastroesophageal reflux 32 occasional (7.5%) HP:0002020
25 pulmonary arterial hypertension 32 occasional (7.5%) HP:0002092
26 platyspondyly 32 HP:0000926
27 congestive heart failure 32 occasional (7.5%) HP:0001635
28 rhizomelia 32 HP:0008905
29 generalized seizures 59 Very frequent (99-80%)
30 otitis media 32 HP:0000388
31 severe short stature 32 HP:0003510
32 redundant skin 32 HP:0001582
33 midface retrusion 32 HP:0011800
34 wide anterior fontanel 32 HP:0000260
35 lumbar hyperlordosis 32 HP:0002938
36 mesomelia 32 HP:0003027
37 central apnea 32 HP:0002871
38 exotropia 32 occasional (7.5%) HP:0000577
39 high myopia 32 occasional (7.5%) HP:0011003
40 generalized-onset seizure 32 hallmark (90%) HP:0002197

UMLS symptoms related to Achondroplasia, Severe, with Developmental Delay and Acanthosis Nigricans:


seizures

MGI Mouse Phenotypes related to Achondroplasia, Severe, with Developmental Delay and Acanthosis Nigricans:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 behavior/neurological MP:0005386 9.35 CLSTN2 FGFR3 JAK1 SPRED1 STAT1
2 limbs/digits/tail MP:0005371 8.92 FGFR3 JAK1 SPRED1 STAT1

Drugs & Therapeutics for Achondroplasia, Severe, with Developmental Delay and Acanthosis...

Search Clinical Trials , NIH Clinical Center for Achondroplasia, Severe, with Developmental Delay and Acanthosis Nigricans

Cochrane evidence based reviews: achondroplasia

Genetic Tests for Achondroplasia, Severe, with Developmental Delay and Acanthosis...

Genetic tests related to Achondroplasia, Severe, with Developmental Delay and Acanthosis Nigricans:

# Genetic test Affiliating Genes
1 Severe Achondroplasia with Developmental Delay and Acanthosis Nigricans 29 FGFR3

Anatomical Context for Achondroplasia, Severe, with Developmental Delay and Acanthosis...

MalaCards organs/tissues related to Achondroplasia, Severe, with Developmental Delay and Acanthosis Nigricans:

41
Skin, Brain, Bone, Heart, Cerebellum, Kidney, Spinal Cord

Publications for Achondroplasia, Severe, with Developmental Delay and Acanthosis...

Articles related to Achondroplasia, Severe, with Developmental Delay and Acanthosis Nigricans:

# Title Authors Year
1
Mutant FGFR3 associated with SADDAN disease causes cytoskeleton disorganization through PLCĪ³1/Src-mediated paxillin hyperphosphorylation. ( 29242050 )
2018
2
Suppression of severe achondroplasia with developmental delay and acanthosis nigricans by the p.Thr651Pro mutation. ( 24352917 )
2014
3
Prenatal and postnatal presentation of severe achondroplasia with developmental delay and acanthosis nigricans (SADDAN) due to the FGFR3 Lys650Met mutation. ( 18076102 )
2008
4
Severe achondroplasia with developmental delay and acanthosis nigricans (SADDAN): phenotypic analysis of a new skeletal dysplasia caused by a Lys650Met mutation in fibroblast growth factor receptor 3. ( 10377013 )
1999

Variations for Achondroplasia, Severe, with Developmental Delay and Acanthosis...

UniProtKB/Swiss-Prot genetic disease variations for Achondroplasia, Severe, with Developmental Delay and Acanthosis Nigricans:

75
# Symbol AA change Variation ID SNP ID
1 FGFR3 p.Lys650Met VAR_004161 rs121913105

Expression for Achondroplasia, Severe, with Developmental Delay and Acanthosis...

Search GEO for disease gene expression data for Achondroplasia, Severe, with Developmental Delay and Acanthosis Nigricans.

Pathways for Achondroplasia, Severe, with Developmental Delay and Acanthosis...

Pathways related to Achondroplasia, Severe, with Developmental Delay and Acanthosis Nigricans according to KEGG:

37
# Name Kegg Source Accession
1 MAPK signaling pathway hsa04010
2 Ras signaling pathway hsa04014
3 Rap1 signaling pathway hsa04015
4 PI3K-Akt signaling pathway hsa04151
5 Regulation of actin cytoskeleton hsa04810

Pathways related to Achondroplasia, Severe, with Developmental Delay and Acanthosis Nigricans according to GeneCards Suite gene sharing:

(show all 31)
# Super pathways Score Top Affiliating Genes
1
Show member pathways
12.92 FGFR3 JAK1 SPRED1 STAT1
2
Show member pathways
12.7 FGFR3 JAK1 STAT1
3
Show member pathways
12.63 FGFR3 JAK1 STAT1
4 12.5 FGFR3 JAK1 STAT1
5 11.79 FGFR3 JAK1
6
Show member pathways
11.79 FGFR3 JAK1 STAT1
7 11.76 JAK1 STAT1
8
Show member pathways
11.76 JAK1 STAT1
9 11.74 JAK1 STAT1
10 11.67 JAK1 STAT1
11
Show member pathways
11.67 FGFR3 JAK1 STAT1
12 11.57 JAK1 STAT1
13
Show member pathways
11.54 JAK1 STAT1
14 11.42 JAK1 STAT1
15 11.4 FGFR3 STAT1
16
Show member pathways
11.34 JAK1 STAT1
17
Show member pathways
11.34 JAK1 SPRED1 STAT1
18 11.33 JAK1 STAT1
19
Show member pathways
11.31 JAK1 STAT1
20 11.3 JAK1 STAT1
21 11.22 JAK1 STAT1
22
Show member pathways
11.2 JAK1 STAT1
23 11.19 JAK1 STAT1
24 11.14 JAK1 STAT1
25
Show member pathways
11.08 JAK1 STAT1
26 11.03 JAK1 STAT1
27
Show member pathways
10.96 JAK1 STAT1
28
Show member pathways
10.93 JAK1 SPRED1 STAT1
29 10.89 JAK1 STAT1
30
Show member pathways
10.62 JAK1 STAT1
31 10.43 JAK1 STAT1

GO Terms for Achondroplasia, Severe, with Developmental Delay and Acanthosis...

Biological processes related to Achondroplasia, Severe, with Developmental Delay and Acanthosis Nigricans according to GeneCards Suite gene sharing:

(show all 11)
# Name GO ID Score Top Affiliating Genes
1 MAPK cascade GO:0000165 9.58 FGFR3 JAK1 SPRED1
2 negative regulation of angiogenesis GO:0016525 9.49 SPRED1 STAT1
3 fibroblast growth factor receptor signaling pathway GO:0008543 9.48 FGFR3 SPRED1
4 interferon-gamma-mediated signaling pathway GO:0060333 9.46 JAK1 STAT1
5 type I interferon signaling pathway GO:0060337 9.43 JAK1 STAT1
6 interleukin-6-mediated signaling pathway GO:0070102 9.37 JAK1 STAT1
7 regulation of interferon-gamma-mediated signaling pathway GO:0060334 9.32 JAK1 STAT1
8 interleukin-27-mediated signaling pathway GO:0070106 9.26 JAK1 STAT1
9 interleukin-35-mediated signaling pathway GO:0070757 9.16 JAK1 STAT1
10 interleukin-9-mediated signaling pathway GO:0038113 8.96 JAK1 STAT1
11 interleukin-21-mediated signaling pathway GO:0038114 8.62 JAK1 STAT1

Molecular functions related to Achondroplasia, Severe, with Developmental Delay and Acanthosis Nigricans according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 Ras guanyl-nucleotide exchange factor activity GO:0005088 8.96 FGFR3 JAK1
2 CCR5 chemokine receptor binding GO:0031730 8.62 JAK1 STAT1

Sources for Achondroplasia, Severe, with Developmental Delay and Acanthosis...

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 ExPASy
19 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
40 LOVD
42 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
54 NINDS
55 Novoseek
57 OMIM
58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 SNOMED-CT via Orphanet
71 TGDB
72 Tocris
73 UMLS
74 UMLS via Orphanet
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