SADDAN
MCID: ACH043
MIFTS: 58

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

Categories: Bone diseases, Fetal diseases, Genetic 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 43 72 70
Saddan 57 12 73 20 43 58 72 36 15 39
Severe Achondroplasia with Developmental Delay and Acanthosis Nigricans 12 20 43 29 6
Saddan Dysplasia 57 12 20 43 72
Severe Achondroplasia-Developmental Delay-Acanthosis Nigricans Syndrome 20 58
Ssb Syndrome 20 43
Skeleton Skin Brain Syndrome 20
Skeleton-Skin-Brain Syndrome 43
Achondroplasia 44

Characteristics:

Orphanet epidemiological data:

58
severe achondroplasia-developmental delay-acanthosis nigricans syndrome
Inheritance: Autosomal dominant,Not applicable; Prevalence: <1/1000000 (Worldwide); Age of onset: Childhood;

OMIM®:

57 (Updated 05-Apr-2021)
Inheritance:
autosomal dominant

Miscellaneous:
clinical overlap with thanatophoric dysplasia i and severe achondroplasia


HPO:

31
achondroplasia, severe, with developmental delay and acanthosis nigricans:
Inheritance autosomal dominant inheritance


Classifications:

Orphanet: 58  
Rare bone diseases
Rare skin diseases
Developmental anomalies during embryogenesis


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

MedlinePlus Genetics : 43 SADDAN (severe achondroplasia with developmental delay and acanthosis nigricans) is a rare disorder of bone growth characterized by skeletal, brain, and skin abnormalities.All people with this condition have extremely short stature with particularly short arms and legs. Other features include unusual bowing of the leg bones; a small chest with short ribs and curved collar bones; short, broad fingers; and folds of extra skin on the arms and legs. Structural abnormalities of the brain cause seizures, profound developmental delay, and intellectual disability. Several affected individuals also have had episodes in which their breathing slows or stops for short periods (apnea). Acanthosis nigricans, a progressive skin disorder characterized by thick, dark, velvety skin, is another characteristic feature of SADDAN that develops in infancy or early childhood.

MalaCards based summary : Achondroplasia, Severe, with Developmental Delay and Acanthosis Nigricans, also known as saddan, is related to achondroplasia and hypochondroplasia, 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. The drugs Natriuretic Peptide, C-Type and mometasone furoate have been mentioned in the context of this disorder. Affiliated tissues include skin, brain and cerebellum, and related phenotypes are intellectual disability, severe and aplasia/hypoplasia of the mandible

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

GARD : 20 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs. Orpha Number: 85165 Definition Severe achondroplasia- developmental delay - acanthosis nigricans syndrome is characterised by the association of severe achondroplasia with developmental delay and acanthosis nigricans. It has been described in four unrelated individuals. Structural central nervous system anomalies, seizures and hearing loss were also reported, together with bowing of the clavicle, femur, tibia and fibula in some cases. The syndrome is caused by a Lys650Met substitution in the kinase domain of fibroblast growth factor receptor 3 (encoded by the FGFR3 gene ; 4p16.3).

KEGG : 36 SADDAN (severe achondroplasia with developmental delay and acanthosis nigricans) is a rare skeletal dysplasia caused by a Lys650Met mutation in fibroblast growth factor receptor 3 (FGFR3).

UniProtKB/Swiss-Prot : 72 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.

Wikipedia : 73 Severe achondroplasia with developmental delay and acanthosis nigricans (SADDAN), is a very rare genetic... more...

More information 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 298)
# Related Disease Score Top Affiliating Genes
1 achondroplasia 32.8 NPPC FGFR3 FGFR2 FGFR1
2 hypochondroplasia 31.1 NPPC FGFR4 FGFR3 FGFR2 FGFR1 FGF1
3 skeletal dysplasias 30.7 TRAPPC2 NPPC FGFR3
4 thanatophoric dysplasia, type ii 30.3 STAT1 FGFR3
5 synostosis 30.3 FGFR3 FGFR2 FGFR1
6 nevus, epidermal 30.0 FGFR4 FGFR3 FGFR2 FGFR1
7 plagiocephaly 29.9 FGFR3 FGFR2 FGFR1
8 dysostosis 29.9 FGFR3 FGFR2 FGFR1
9 craniosynostosis 29.8 FGFR4 FGFR3 FGFR2 FGFR1 FGF1
10 camptodactyly-tall stature-scoliosis-hearing loss syndrome 29.8 NPPC FGFR3
11 osteochondroma 29.7 FGFR3 FGFR1
12 muenke syndrome 29.7 FGFR3 FGFR2 FGFR1
13 acromesomelic dysplasia 29.6 NPPC FGFR3
14 acromesomelic dysplasia, maroteaux type 29.6 NPPC FGFR3
15 pfeiffer syndrome 29.6 FGFR3 FGFR2 FGFR1
16 bone disease 29.5 TRAPPC2 STAT1 FGFR3 FGFR2 FGFR1
17 thanatophoric dysplasia, type i 29.4 STAT1 NPPC FRS2 FGFR4 FGFR3 FGFR2
18 crouzon syndrome 28.7 FRS2 FGFR4 FGFR3 FGFR2 FGFR1 FGF16
19 odontochondrodysplasia 28.4 TRIP11 TRAPPC2 STAT1 NPPC FGFR4 FGFR3
20 lacrimoauriculodentodigital syndrome 28.3 FRS2 FGFR4 FGFR3 FGFR2 FGFR1 FGF16
21 short-limb skeletal dysplasia with severe combined immunodeficiency 11.6
22 dwarfism 11.3
23 pseudoachondroplasia 11.0
24 mesomelia 10.9
25 atelosteogenesis, type i 10.9
26 boomerang dysplasia 10.9
27 hydrocephalus, congenital, 1 10.9
28 hydrocephalus 10.5
29 spinal stenosis 10.5
30 sleep apnea 10.4
31 hemifacial hyperplasia 10.3 FGFR3 FGFR2
32 acanthosis nigricans 10.2
33 testicular spermatocytic seminoma 10.2 FGFR3 FGFR2
34 dacryocystocele 10.2 FGFR3 FGFR2
35 chronic inflammation of lacrimal passage 10.2 FGFR3 FGFR2
36 luteoma 10.2 FGFR3 FGFR2
37 craniosynostosis 1 10.2
38 hypotonia 10.2
39 synovial chondromatosis 10.2 FGFR3 FGFR1
40 acanthoma 10.2 FGFR3 FGFR2
41 otitis media 10.2
42 down syndrome 10.2
43 overgrowth syndrome 10.1
44 fgfr craniosynostosis syndromes 10.1 FGFR3 FGFR2 FGFR1
45 scoliosis 10.1
46 syndromic craniosynostosis 10.1 FGFR3 FGFR2 FGFR1
47 hypertelorism, microtia, facial clefting syndrome 10.1 FGFR3 FGFR2 FGFR1
48 radioulnar synostosis 10.1 FGFR3 FGFR2 FGFR1
49 antley-bixler syndrome 10.1 FGFR3 FGFR2 FGFR1
50 apert syndrome 10.1 FGFR3 FGFR2 FGFR1

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...

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

58 31 (show all 40)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 intellectual disability, severe 58 31 hallmark (90%) Very frequent (99-80%) HP:0010864
2 aplasia/hypoplasia of the mandible 58 31 hallmark (90%) Very frequent (99-80%) HP:0009118
3 severe global developmental delay 58 31 hallmark (90%) Very frequent (99-80%) HP:0011344
4 acanthosis nigricans 58 31 hallmark (90%) Very frequent (99-80%) HP:0000956
5 hypoplasia of the corpus callosum 58 31 hallmark (90%) Very frequent (99-80%) HP:0002079
6 generalized-onset seizure 58 31 hallmark (90%) Very frequent (99-80%) HP:0002197
7 brain atrophy 58 31 hallmark (90%) Very frequent (99-80%) HP:0012444
8 metaphyseal chondrodysplasia 58 31 hallmark (90%) Very frequent (99-80%) HP:0005871
9 enlarged cerebellum 58 31 hallmark (90%) Very frequent (99-80%) HP:0012081
10 microcephaly 58 31 frequent (33%) Frequent (79-30%) HP:0000252
11 femoral bowing 58 31 frequent (33%) Frequent (79-30%) HP:0002980
12 tibial bowing 58 31 frequent (33%) Frequent (79-30%) HP:0002982
13 fibular bowing 58 31 frequent (33%) Frequent (79-30%) HP:0010502
14 abnormal clavicle morphology 31 frequent (33%) HP:0000889
15 gastroesophageal reflux 31 occasional (7.5%) HP:0002020
16 congestive heart failure 31 occasional (7.5%) HP:0001635
17 pulmonary arterial hypertension 31 occasional (7.5%) HP:0002092
18 high myopia 31 occasional (7.5%) HP:0011003
19 exotropia 31 occasional (7.5%) HP:0000577
20 intellectual disability 31 HP:0001249
21 megalencephaly 31 HP:0001355
22 frontal bossing 31 HP:0002007
23 kyphosis 31 HP:0002808
24 sleep apnea 31 HP:0010535
25 hydrocephalus 31 HP:0000238
26 hearing impairment 31 HP:0000365
27 global developmental delay 31 HP:0001263
28 depressed nasal bridge 31 HP:0005280
29 platyspondyly 31 HP:0000926
30 otitis media 31 HP:0000388
31 redundant skin 31 HP:0001582
32 abnormality of the clavicle 58 Frequent (79-30%)
33 midface retrusion 31 HP:0011800
34 wide anterior fontanel 31 HP:0000260
35 severe short stature 31 HP:0003510
36 rhizomelia 31 HP:0008905
37 central apnea 31 HP:0002871
38 mesomelia 31 HP:0003027
39 lumbar hyperlordosis 31 HP:0002938
40 seizure 31 HP:0001250

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Apr-2021)
Neurologic Central Nervous System:
seizures
hydrocephalus
central apnea
developmental delay
thin corpus callosum
more
Head And Neck Face:
frontal bossing
midface hypoplasia

Respiratory:
sleep apnea
respiratory compromise at birth

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

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

Cardiovascular Vascular:
pulmonary hypertension (in some patients)

Abdomen Gastrointestinal:
gastroesophageal reflux (in some patients)

Chest External Features:
small chest with flaring costal margins

Skeletal Pelvis:
posterior rotation of hips

Head And Neck Head:
megalencephaly
large anterior fontanel

Skeletal Spine:
kyphosis
platyspondyly
lumbar lordosis
cervical spinal stenosis

Head And Neck Nose:
depressed nasal bridge

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

Growth Height:
dwarfism
short stature, severe disproportionate

Head And Neck Eyes:
exotropia (in some patients)
high myopia (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 (Updated 05-Apr-2021)

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


seizures

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

26
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Decreased human cytomegalovirus (HCMV) strain AD169 replication GR00248-A 8.92 FGFR1 FGFR2 FGFR3 FGFR4

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

46
# Description MGI Source Accession Score Top Affiliating Genes
1 cellular MP:0005384 10.06 FGF16 FGFR1 FGFR2 FGFR3 FGFR4 FRS2
2 growth/size/body region MP:0005378 10.06 FGF16 FGFR1 FGFR2 FGFR3 FGFR4 FRS2
3 craniofacial MP:0005382 9.98 FGF16 FGFR1 FGFR2 FGFR3 FRS2 NPPC
4 nervous system MP:0003631 9.91 CLSTN2 FGF1 FGFR1 FGFR2 FGFR3 FRS2
5 limbs/digits/tail MP:0005371 9.87 FGFR1 FGFR2 FGFR3 FRS2 NPPC STAT1
6 hearing/vestibular/ear MP:0005377 9.85 FGF16 FGFR1 FGFR2 FGFR3 FGFR4 FRS2
7 reproductive system MP:0005389 9.7 FGF16 FGFR1 FGFR2 FGFR3 FGFR4 NPPC
8 respiratory system MP:0005388 9.43 FGFR2 FGFR3 FGFR4 STAT1 TRAPPC2 TRIP11
9 skeleton MP:0005390 9.17 FGFR1 FGFR2 FGFR3 FGFR4 NPPC STAT1

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

Drugs for Achondroplasia, Severe, with Developmental Delay and Acanthosis Nigricans (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 13)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1 Natriuretic Peptide, C-Type Phase 3
2
mometasone furoate Approved, Investigational, Vet_approved Phase 2 83919-23-7
3
Tyrosine Approved, Investigational, Nutraceutical Phase 2 60-18-4 6057
4
Resveratrol Investigational Phase 2 501-36-0 445154
5 Mitogens Phase 2
6 Analgesics, Non-Narcotic Phase 2
7 Analgesics Phase 2
8 Antirheumatic Agents Phase 2
9 Antioxidants Phase 2
10 Anti-Inflammatory Agents Phase 2
11 Anti-Inflammatory Agents, Non-Steroidal Phase 2
12 Platelet Aggregation Inhibitors Phase 2
13 Protective Agents Phase 2

Interventional clinical trials:

(show all 25)
# Name Status NCT ID Phase Drugs
1 A Phase 3 Randomized, Double-Blind, Placebo-Controlled, Multicenter Study to Evaluate the Efficacy and Safety of BMN 111 in Children With Achondroplasia Completed NCT03197766 Phase 3 BMN 111;Placebo
2 A Phase 3, Open-Label Long-Term Extension Study to Evaluate the Safety and Efficacy of BMN 111 in Children With Achondroplasia Active, not recruiting NCT03424018 Phase 3 BMN 111
3 A Phase 2, Open-label, Sequential Cohort Dose-escalation Study of BMN 111 in Children With Achondroplasia Completed NCT02055157 Phase 2 BMN 111
4 A PHASE 2 MULTIPLE DOSE, RANDOMIZED STUDY TO ASSESS THE SAFETY, TOLERABILITY, PHARMACOKINETICS AND EFFICACY OF RECIFERCEPT IN CHILDREN WITH ACHONDROPLASIA Recruiting NCT04638153 Phase 2
5 A Randomized, Controlled, Open-label Clinical Trial With an Open-label Extension to Investigate the Safety of Vosoritide in Infants and Young Children With Achondroplasia at Risk of Requiring Cervicomedullary Decompression Surgery Recruiting NCT04554940 Phase 2
6 Phase 2, Open-Label, Dose-Escalation and Dose-Expansion Study of Infigratinib, an FGFR 1-3-Selective Tyrosine Kinase Inhibitor, in Children With Achondroplasia: PROPEL 2 Recruiting NCT04265651 Phase 2 Infigratinib 0.016 mg/kg;Infigratinib 0.032 mg/kg;Infigratinib 0.064 mg/kg;Infigratinib 0.128 mg/kg
7 Resveratrol Trial for Relief of Pain in Pseudoachondroplasia Recruiting NCT03866200 Phase 2 resveratrol;Placebo
8 A Phase 2, Open-Label, Extension Study to Evaluate the Long-Term Safety, Tolerability, and Efficacy of BMN 111 in Children With Achondroplasia Active, not recruiting NCT02724228 Phase 2 BMN 111
9 A Phase 2 Randomized, Double-Blind, Placebo-Controlled Clinical Trial to Evaluate the Safety and Efficacy of BMN 111 in Infants and Young Children With Achondroplasia, Age 0 to < 60 Months Enrolling by invitation NCT03583697 Phase 2 BMN 111;Placebo
10 A Phase 2 Open-Label Long-Term Extension Study to Evaluate the Safety and Efficacy of BMN 111 in Children With Achondroplasia Enrolling by invitation NCT03989947 Phase 2 Active BMN 111: Daily subcutaneous injection of 15 ug/kg of BMN 111
11 ACcomplisH: A Phase 2, Multicenter, Double-blind, Randomized, Placebo-controlled, Dose Escalation Trial Evaluating Safety, Efficacy, and Pharmacokinetics of Subcutaneous Doses of TransCon CNP Administered Once Weekly for 52 Weeks in Prepubertal Children With Achondroplasia Followed by an Open-Label Extension Period Enrolling by invitation NCT04085523 Phase 2 TransCon CNP;Placebo for TransCon CNP
12 A Phase 1, Two-Part, Double-Blind, Placebo-Controlled Study to Evaluate Safety, Tolerability, and Pharmacokinetics of Single and Multiple Doses of BMN 111 Administered to Healthy Adult Volunteers Completed NCT01590446 Phase 1 BMN 111;Normal Saline
13 C-Type Natriuretic Peptide and Achondroplasia Completed NCT01541306
14 Issues Surrounding Prenatal Genetic Testing for Achondroplasia Completed NCT00001536
15 Lifetime Impact Study for Achondroplasia (LISA) Completed NCT03872531
16 The Impact of Achondroplasia on Quality of Life, Healthcare Resource Use, Clinical, Socio-economic and Psychosocial State of the Individual. Completed NCT03449368
17 Open-label, Multicenter, Observational, Non-intervention Study to Retrospectively Evaluate the Efficacy of Norditropin® (Adult Height) in Patients With Achondroplasia/Hypochondroplasia Enrolled in the GH-1941 Study [Follow-up Survey] Completed NCT01435629 somatropin
18 Specific Survey of Norditropin® in Achondroplasia: Survey for Long-term Application Completed NCT01516229 somatropin
19 A Multi-center, Prospective, Longitudinal, Observational Study to Investigate the Clinical and Anthropometric Characteristics of Children With the Diagnosis Achondroplasia. Recruiting NCT03794609
20 ACHieve: A Multi-center, Longitudinal, Observational Study of Children With Achondroplasia Recruiting NCT03875534
21 Retrospective Clinical Study to Evaluate of Cranio-vertebral Abnormalities Through Radiological Analysis in Patients With Achondroplasia Treated/Followed at the Hôpital Femme Mère Enfant Recruiting NCT04184817
22 Prospective Clinical Assessment Study in Children With Achondroplasia: The PROPEL Trial Recruiting NCT04035811
23 The Norwegian Adult Achondroplasia Study Active, not recruiting NCT03780153
24 Achondroplasia Natural History Multicenter Clinical Study Enrolling by invitation NCT02597881
25 A Multicenter, Multinational Clinical Assessment Study for Pediatric Patients With Achondroplasia Enrolling by invitation NCT01603095

Search 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:

40
Skin, Brain, Cerebellum, Heart, Bone Marrow

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

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

(show all 29)
# Title Authors PMID Year
1
Prenatal and postnatal presentation of severe achondroplasia with developmental delay and acanthosis nigricans (SADDAN) due to the FGFR3 Lys650Met mutation. 57 61
18076102 2008
2
Highly activated Fgfr3 with the K644M mutation causes prolonged survival in severe dwarf mice. 61 57
11406607 2001
3
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. 61 57
10377013 1999
4
A novel skeletal dysplasia with developmental delay and acanthosis nigricans is caused by a Lys650Met mutation in the fibroblast growth factor receptor 3 gene. 57 61
10053006 1999
5
Novel FGFR3 mutations creating cysteine residues in the extracellular domain of the receptor cause achondroplasia or severe forms of hypochondroplasia. 6
16912704 2006
6
Mutant FGFR3 associated with SADDAN disease causes cytoskeleton disorganization through PLCγ1/Src-mediated paxillin hyperphosphorylation. 61
29242050 2018
7
A new genus and species of scorpion from Burma [Myanmar] (Scorpiones: Scorpiopidae): Implications for the taxonomy of the family. 61
28668484 2017
8
Achondroplasia: Development, pathogenesis, and therapy. 61
27987249 2017
9
Mild achondroplasia/hypochondroplasia with acanthosis nigricans, normal development, and a p.Ser348Cys FGFR3 mutation. 61
28181399 2017
10
FGFR3-related condition: a skeletal dysplasia with similarities to thanatophoric dysplasia and SADDAN due to Lys650Met. 61
25119967 2015
11
The paradox of FGFR3 signaling in skeletal dysplasia: why chondrocytes growth arrest while other cells over proliferate. 61
24295726 2014
12
Suppression of severe achondroplasia with developmental delay and acanthosis nigricans by the p.Thr651Pro mutation. 61
24352917 2014
13
Hypochondroplasia, Acanthosis Nigricans, and Insulin Resistance in a Child with FGFR3 Mutation: Is It Just an Association? 61
25505998 2014
14
Meclozine facilitates proliferation and differentiation of chondrocytes by attenuating abnormally activated FGFR3 signaling in achondroplasia. 61
24324705 2013
15
FGFR3 related skeletal dysplasias diagnosed prenatally by ultrasonography and molecular analysis: presentation of 17 cases. 61
21910223 2011
16
SADDAN syndrome. 61
22145492 2011
17
Review of the recently defined molecular mechanisms underlying thanatophoric dysplasia and their potential therapeutic implications for achondroplasia. 61
20034074 2010
18
Acanthosis nigricans and insulin sensitivity in patients with achondroplasia and hypochodroplasia due to FGFR3 mutations. 61
19622626 2009
19
Enumeration of the colony-forming units-fibroblast from mouse and human bone marrow in normal and pathological conditions. 61
19383412 2009
20
[Case of a Japanese female presenting severe achondroplasia with developmental delay and acanthosis nigricans (SADDAN) syndrome with a K650M mutation in the fibroblast growth factor receptor 3 gene]. 61
19039991 2008
21
Frequent activating FGFR2 mutations in endometrial carcinomas parallel germline mutations associated with craniosynostosis and skeletal dysplasia syndromes. 61
17525745 2007
22
Familial acanthosis nigricans due to K650T FGFR3 mutation. 61
17875876 2007
23
Sustained phosphorylation of mutated FGFR3 is a crucial feature of genetic dwarfism and induces apoptosis in the ATDC5 chondrogenic cell line via PLCgamma-activated STAT1. 61
17561467 2007
24
K644E/M FGFR3 mutants activate Erk1/2 from the endoplasmic reticulum through FRS2 alpha and PLC gamma-independent pathways. 61
16476447 2006
25
The kinase activity of fibroblast growth factor receptor 3 with activation loop mutations affects receptor trafficking and signaling. 61
15292251 2004
26
Novel fibroblast growth factor receptor 3 (FGFR3) mutations in bladder cancer previously identified in non-lethal skeletal disorders. 61
12461689 2002
27
Some chondrodysplasias with short limbs: molecular perspectives. 61
12357475 2002
28
Distinct missense mutations of the FGFR3 lys650 codon modulate receptor kinase activation and the severity of the skeletal dysplasia phenotype. 61
11055896 2000
29
The molecular and genetic basis of fibroblast growth factor receptor 3 disorders: the achondroplasia family of skeletal dysplasias, Muenke craniosynostosis, and Crouzon syndrome with acanthosis nigricans. 61
10696568 2000

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

ClinVar genetic disease variations for Achondroplasia, Severe, with Developmental Delay and Acanthosis Nigricans:

6
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 FGFR3 NM_001163213.1(FGFR3):c.746C>G (p.Ser249Cys) SNV Pathogenic 16339 rs121913483 GRCh37: 4:1803568-1803568
GRCh38: 4:1801841-1801841
2 FGFR3 NM_000142.5(FGFR3):c.1949A>C (p.Lys650Thr) SNV Pathogenic 65855 rs121913105 GRCh37: 4:1807890-1807890
GRCh38: 4:1806163-1806163
3 FGFR3 NM_000142.5(FGFR3):c.742C>T (p.Arg248Cys) SNV Pathogenic 16332 rs121913482 GRCh37: 4:1803564-1803564
GRCh38: 4:1801837-1801837
4 FGFR3 NM_000142.5(FGFR3):c.749C>G (p.Pro250Arg) SNV Pathogenic 16340 rs4647924 GRCh37: 4:1803571-1803571
GRCh38: 4:1801844-1801844
5 FGFR3 NM_000142.5(FGFR3):c.1138G>A SNV Pathogenic 16327 rs28931614 GRCh37: 4:1806119-1806119
GRCh38: 4:1804392-1804392
6 FGFR3 NM_000142.5(FGFR3):c.1620C>G (p.Asn540Lys) SNV Pathogenic 16338 rs28933068 GRCh37: 4:1807371-1807371
GRCh38: 4:1805644-1805644
7 FGFR3 NM_000142.5(FGFR3):c.251C>T (p.Ser84Leu) SNV Pathogenic 16358 rs121913116 GRCh37: 4:1801122-1801122
GRCh38: 4:1799395-1799395
8 FGFR3 NM_000142.5(FGFR3):c.200G>A (p.Gly67Asp) SNV Uncertain significance 546226 rs369232922 GRCh37: 4:1801071-1801071
GRCh38: 4:1799344-1799344
9 FGFR3 NM_000142.5(FGFR3):c.1993G>T (p.Ala665Ser) SNV Uncertain significance 465350 rs764892330 GRCh37: 4:1808017-1808017
GRCh38: 4:1806290-1806290
10 FGFR3 NM_000142.5(FGFR3):c.2153A>G (p.Asn718Ser) SNV Uncertain significance 521225 rs139773438 GRCh37: 4:1808395-1808395
GRCh38: 4:1806668-1806668

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

72
# 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:

36
# 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 top 50) (show all 55)
# Super pathways Score Top Affiliating Genes
1
Show member pathways
13.91 STAT1 FRS2 FGFR4 FGFR3 FGFR2 FGFR1
2
Show member pathways
13.72 STAT1 FGFR4 FGFR3 FGFR2 FGFR1 FGF16
3
Show member pathways
13.63 STAT1 FRS2 FGFR4 FGFR3 FGFR2 FGFR1
4
Show member pathways
13.61 STAT1 FGFR4 FGFR3 FGFR2 FGFR1 FGF16
5
Show member pathways
13.46 STAT1 FGFR4 FGFR3 FGFR2 FGFR1 FGF16
6
Show member pathways
13.44 FGFR4 FGFR3 FGFR2 FGFR1 FGF16 FGF1
7
Show member pathways
13.42 FRS2 FGFR4 FGFR3 FGFR2 FGFR1 FGF16
8
Show member pathways
13.38 FRS2 FGFR4 FGFR3 FGFR2 FGFR1 FGF16
9
Show member pathways
13.35 STAT1 FGFR4 FGFR3 FGFR2 FGFR1 FGF16
10
Show member pathways
13.31 STAT1 FRS2 FGFR4 FGFR3 FGFR2 FGFR1
11
Show member pathways
13.25 FGFR4 FGFR3 FGFR2 FGFR1 FGF16 FGF1
12
Show member pathways
13.23 FGFR4 FGFR3 FGFR2 FGFR1 FGF16 FGF1
13
Show member pathways
13.21 FGFR4 FGFR3 FGFR2 FGFR1 FGF16 FGF1
14
Show member pathways
13.1 FRS2 FGFR4 FGFR3 FGFR2 FGFR1 FGF16
15
Show member pathways
13.02 FGFR4 FGFR3 FGFR2 FGFR1 FGF16 FGF1
16
Show member pathways
13.02 STAT1 FGFR4 FGFR3 FGFR2 FGFR1 FGF16
17
Show member pathways
12.96 STAT1 FGFR4 FGFR3 FGFR2 FGFR1 FGF16
18
Show member pathways
12.85 FGFR4 FGFR3 FGFR2 FGFR1
19
Show member pathways
12.83 FRS2 FGFR4 FGFR3 FGFR2 FGFR1 FGF16
20 12.81 STAT1 FGFR4 FGFR3 FGFR2 FGFR1 FGF16
21
Show member pathways
12.76 FGFR4 FGFR3 FGFR2 FGFR1
22 12.76 FGFR4 FGFR3 FGFR2 FGFR1 FGF16 FGF1
23
Show member pathways
12.73 FGFR4 FGFR3 FGFR2 FGFR1 FGF16 FGF1
24
Show member pathways
12.7 FGFR4 FGFR3 FGFR2 FGFR1 FGF16 FGF1
25
Show member pathways
12.68 FGFR2 FGFR1 FGF16 FGF1
26
Show member pathways
12.66 FRS2 FGFR4 FGFR3 FGFR2 FGFR1 FGF16
27 12.63 FGFR4 FGFR3 FGFR2 FGFR1 FGF16 FGF1
28
Show member pathways
12.61 FGFR2 FGFR1 FGF16 FGF1
29
Show member pathways
12.51 STAT1 FGFR4 FGFR3 FGFR2 FGFR1
30
Show member pathways
12.49 FRS2 FGFR4 FGFR3 FGFR2 FGFR1 FGF16
31
Show member pathways
12.46 FGFR4 FGFR3 FGFR2 FGFR1
32
Show member pathways
12.41 FGFR4 FGFR3 FGFR2 FGFR1
33
Show member pathways
12.4 FGFR4 FGFR3 FGFR2 FGFR1 FGF16 FGF1
34
Show member pathways
12.38 FGFR4 FGFR3 FGFR2 FGFR1 FGF16 FGF1
35 12.37 FGFR4 FGFR3 FGFR2 FGFR1 FGF16 FGF1
36
Show member pathways
12.26 FRS2 FGFR4 FGFR3 FGFR2 FGFR1 FGF16
37
Show member pathways
12.21 STAT1 FGFR4 FGFR3 FGFR2 FGFR1 FGF16
38
Show member pathways
12.21 FRS2 FGFR4 FGFR3 FGFR2 FGFR1 FGF16
39
Show member pathways
12.19 FGFR4 FGFR3 FGFR2 FGFR1
40 12.1 FGFR4 FGFR3 FGFR2 FGFR1
41 12.05 FRS2 FGFR4 FGFR3 FGFR2 FGFR1 FGF1
42
Show member pathways
11.99 FRS2 FGFR4 FGFR3 FGFR2 FGFR1 FGF16
43 11.89 FGFR3 FGFR2 FGFR1
44
Show member pathways
11.89 STAT1 FRS2 FGFR1 FGF1
45 11.84 FGFR4 FGFR3 FGFR2 FGFR1 FGF1
46 11.76 FGFR4 FGFR3 FGFR1
47 11.73 FGFR4 FGFR3 FGFR2 FGFR1 FGF16 FGF1
48 11.7 FGFR3 FGFR2 FGFR1
49 11.66 STAT1 FGFR3 FGFR1
50
Show member pathways
11.61 FGFR3 FGF16 FGF1

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

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

# Name GO ID Score Top Affiliating Genes
1 cytoplasm GO:0005737 9.96 TRIP11 TRAPPC2 STAT1 FRS2 FGFR4 FGFR3
2 extracellular region GO:0005576 9.7 NPPC FGFR4 FGFR3 FGFR2 FGFR1 FGF16
3 transport vesicle GO:0030133 9.13 TRIP11 FGFR4 FGFR3
4 receptor complex GO:0043235 8.92 FGFR4 FGFR3 FGFR2 FGFR1

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

(show all 24)
# Name GO ID Score Top Affiliating Genes
1 multicellular organism development GO:0007275 9.98 FGFR4 FGFR3 FGFR2 FGFR1 FGF1
2 protein phosphorylation GO:0006468 9.91 FGFR4 FGFR3 FGFR2 FGFR1
3 positive regulation of cell proliferation GO:0008284 9.8 STAT1 FGFR4 FGFR3 FGFR2 FGFR1 FGF16
4 cell-cell signaling GO:0007267 9.79 FGFR3 FGFR2 FGF16
5 positive regulation of ERK1 and ERK2 cascade GO:0070374 9.78 FGFR4 FGFR3 FGFR2
6 protein autophosphorylation GO:0046777 9.76 FGFR4 FGFR3 FGFR2 FGFR1
7 animal organ morphogenesis GO:0009887 9.74 FGFR2 FGF16 FGF1
8 peptidyl-tyrosine phosphorylation GO:0018108 9.73 FGFR4 FGFR3 FGFR2 FGFR1
9 skeletal system development GO:0001501 9.72 TRAPPC2 FGFR3 FGFR1
10 transmembrane receptor protein tyrosine kinase signaling pathway GO:0007169 9.72 FRS2 FGFR4 FGFR3 FGFR2 FGFR1
11 positive regulation of MAPK cascade GO:0043410 9.71 FGFR3 FGFR2 FGFR1
12 positive regulation of kinase activity GO:0033674 9.71 FGFR4 FGFR3 FGFR2 FGFR1
13 MAPK cascade GO:0000165 9.7 FRS2 FGFR4 FGFR3 FGFR2 FGFR1 FGF16
14 ventricular septum development GO:0003281 9.6 TRIP11 FRS2
15 bone morphogenesis GO:0060349 9.59 FGFR3 FGFR2
16 regulation of ERK1 and ERK2 cascade GO:0070372 9.58 FRS2 FGFR2
17 positive regulation of mesenchymal cell proliferation GO:0002053 9.56 STAT1 FGFR2
18 positive regulation of phospholipase activity GO:0010518 9.54 FGFR3 FGFR2 FGFR1
19 organ induction GO:0001759 9.52 FRS2 FGF1
20 endochondral bone growth GO:0003416 9.51 FGFR3 FGFR2
21 positive regulation of protein kinase B signaling GO:0051897 9.5 FRS2 FGFR4 FGFR3 FGFR2 FGFR1 FGF16
22 prostate epithelial cord arborization involved in prostate glandular acinus morphogenesis GO:0060527 9.49 FRS2 FGFR2
23 positive regulation of endothelial cell chemotaxis to fibroblast growth factor GO:2000546 9.48 FGFR1 FGF16
24 fibroblast growth factor receptor signaling pathway GO:0008543 9.17 FRS2 FGFR4 FGFR3 FGFR2 FGFR1 FGF16

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 protein kinase activity GO:0004672 9.71 FGFR4 FGFR3 FGFR2 FGFR1
2 heparin binding GO:0008201 9.67 FGFR4 FGFR2 FGFR1 FGF1
3 protein tyrosine kinase activity GO:0004713 9.62 FGFR4 FGFR3 FGFR2 FGFR1
4 transmembrane receptor protein tyrosine kinase activity GO:0004714 9.46 FGFR4 FGFR3 FGFR2 FGFR1
5 fibroblast growth factor receptor binding GO:0005104 9.43 FRS2 FGF16 FGF1
6 fibroblast growth factor binding GO:0017134 9.26 FGFR4 FGFR3 FGFR2 FGFR1
7 fibroblast growth factor-activated receptor activity GO:0005007 8.92 FGFR4 FGFR3 FGFR2 FGFR1

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

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