ACH
MCID: ACH004
MIFTS: 66

Achondroplasia (ACH)

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

Aliases & Classifications for Achondroplasia

MalaCards integrated aliases for Achondroplasia:

Name: Achondroplasia 56 12 74 24 52 25 58 73 36 29 13 54 6 15 39 71 32
Ach 56 52 25 73
Achondroplastic Dwarfism 52 25 71
Achondroplastic Physique 12
Osteosclerosis Congenita 12
Dwarf, Achondroplastic 25
Chondrodystrophia 12

Characteristics:

Orphanet epidemiological data:

58
achondroplasia
Inheritance: Autosomal dominant; Prevalence: 1-9/100000 (Worldwide),1-9/100000 (Italy),1-9/100000 (Sweden),1-9/100000 (Spain),1-9/100000 (Denmark),1-9/100000 (United States),1-9/100000 (Latin America),1-9/100000 (Australia); Age of onset: Neonatal; Age of death: elderly;

OMIM:

56
Inheritance:
autosomal dominant

Miscellaneous:
autosomal dominant with complete penetrance
80% cases new mutations
99+% of the mutations are fgfr3, g380r
paternal age effect


HPO:

31
achondroplasia:
Inheritance autosomal dominant inheritance


GeneReviews:

24
Penetrance Penetrance is 100%; all individuals who have an fgfr3 heterozygous pathogenic variant associated with achondroplasia have the clinical manifestations of the disorder.

Classifications:

Orphanet: 58  
Rare bone diseases
Developmental anomalies during embryogenesis


External Ids:

Disease Ontology 12 DOID:4480
OMIM 56 100800
KEGG 36 H01749
MeSH 43 D000130
NCIt 49 C34345
SNOMED-CT 67 86268005
ICD10 32 Q77.4
MESH via Orphanet 44 D000130
ICD10 via Orphanet 33 Q77.4
UMLS via Orphanet 72 C0001080
Orphanet 58 ORPHA15
MedGen 41 C0001080
UMLS 71 C0001080 C2930793

Summaries for Achondroplasia

Genetics Home Reference : 25 Achondroplasia is a form of short-limbed dwarfism. The word achondroplasia literally means "without cartilage formation." Cartilage is a tough but flexible tissue that makes up much of the skeleton during early development. However, in achondroplasia the problem is not in forming cartilage but in converting it to bone (a process called ossification), particularly in the long bones of the arms and legs. Achondroplasia is similar to another skeletal disorder called hypochondroplasia, but the features of achondroplasia tend to be more severe. All people with achondroplasia have short stature. The average height of an adult male with achondroplasia is 131 centimeters (4 feet, 4 inches), and the average height for adult females is 124 centimeters (4 feet, 1 inch). Characteristic features of achondroplasia include an average-size trunk, short arms and legs with particularly short upper arms and thighs, limited range of motion at the elbows, and an enlarged head (macrocephaly) with a prominent forehead. Fingers are typically short and the ring finger and middle finger may diverge, giving the hand a three-pronged (trident) appearance. People with achondroplasia are generally of normal intelligence. Health problems commonly associated with achondroplasia include episodes in which breathing slows or stops for short periods (apnea), obesity, and recurrent ear infections. In childhood, individuals with the condition usually develop a pronounced and permanent sway of the lower back (lordosis) and bowed legs. Some affected people also develop abnormal front-to-back curvature of the spine (kyphosis) and back pain. A potentially serious complication of achondroplasia is spinal stenosis, which is a narrowing of the spinal canal that can pinch (compress) the upper part of the spinal cord. Spinal stenosis is associated with pain, tingling, and weakness in the legs that can cause difficulty with walking. Another uncommon but serious complication of achondroplasia is hydrocephalus, which is a buildup of fluid in the brain in affected children that can lead to increased head size and related brain abnormalities.

MalaCards based summary : Achondroplasia, also known as ach, is related to achondroplasia, severe, with developmental delay and acanthosis nigricans and pseudoachondroplasia. An important gene associated with Achondroplasia is FGFR3 (Fibroblast Growth Factor Receptor 3), and among its related pathways/superpathways are ERK Signaling and Phospholipase-C Pathway. The drugs Simvastatin and Natriuretic Peptide, C-Type have been mentioned in the context of this disorder. Affiliated tissues include long bone, bone and spinal cord, and related phenotypes are bowing of the legs and thoracolumbar kyphosis

Disease Ontology : 12 An osteochondrodysplasia that results in dwarfism which has material basis in abnormal ossification of cartilage in located in long bone.

NIH Rare Diseases : 52 Achondroplasia is a disorder of bone growth that prevents the changing of cartilage (particularly in the long bones of the arms and legs) to bone. It is characterized by dwarfism , limited range of motion at the elbows, large head size (macrocephaly), small fingers, and normal intelligence. Achondroplasia can cause health complications such as interruption of breathing (apnea ), obesity, recurrent ear infections, an exaggerated inward curve of the lumbar spine (lordosis ). More serious problems include a narrowing of the spinal canal that can pinch (compress) the upper part of the spinal cord (spinal stenosis) and a buildup of fluid in the brain (hydrocephalus ). Some people with achondroplasia may have delayed motor development early on, but cognition is normal. Achondroplasia is caused by mutations in the FGFR3 gene . Inheritance is autosomal dominant . Treatment may include medication with growth hormone , and surgery aimed to correct the spine, or bone problems, as well, as to reduce the pressure inside the brain in cases of hydrocephaly. Prognosis with achondroplasia is good except in cases of spinal compression at the neck.

OMIM : 56 Achondroplasia is the most frequent form of short-limb dwarfism. Affected individuals exhibit short stature caused by rhizomelic shortening of the limbs, characteristic facies with frontal bossing and midface hypoplasia, exaggerated lumbar lordosis, limitation of elbow extension, genu varum, and trident hand (summary by Bellus et al., 1995). (100800)

KEGG : 36 Achondroplasia is the most common skeletal dysplasia and the most frequent cause of short-limbed dwarfism. It is usually recognised at birth because of its distinctive clinical and radiographic features. Newborn infants with achondroplasia typically present with disproportionate shortening of the limbs, a long and narrow trunk, a large head with frontal bossing and midface retrusion. This disease is caused by mutations of the transmembrane receptor FGFR3, an important regulator of bone growth. It is inherited in an autosomal dominant manner, but in the majority of cases it results from de novo mutations. The most common complications of achondroplasia are medullary and radicular compressions due to spinal stenosis and deformities of the lower limbs. Most individuals with achondroplasia have normal intelligence.

UniProtKB/Swiss-Prot : 73 Achondroplasia: A frequent form of short-limb dwarfism. It is characterized by 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. ACH is an autosomal dominant disease.

Wikipedia : 74 Achondroplasia is a genetic disorder whose primary feature is dwarfism. In those with the condition, the... more...

GeneReviews: NBK1152

Related Diseases for Achondroplasia

Diseases related to Achondroplasia via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 340)
# Related Disease Score Top Affiliating Genes
1 achondroplasia, severe, with developmental delay and acanthosis nigricans 34.6 NPPC FGFR3 FGFR2 FGFR1
2 pseudoachondroplasia 31.5 COMP COL2A1 ACAN
3 hypochondroplasia 31.1 TK1 SHOX NPPC FGFR3 FGFR2 FGFR1
4 acanthosis nigricans 30.8 IGF1 FGFR3 FGFR2
5 spinal stenosis 30.6 COL2A1 COL1A1 ACAN
6 hydrocephalus 30.6 IGF1 FGFR3 FGFR2 FGFR1
7 thanatophoric dysplasia, type ii 30.6 SPRY2 FGFR3
8 nevus, epidermal 30.6 FGFR3 FGFR2 FGFR1
9 acromesomelic dysplasia, maroteaux type 30.3 SHOX NPPC FGFR3
10 plagiocephaly 30.2 FGFR3 FGFR2 FGFR1
11 synostosis 30.0 MSX2 FGFR3 FGFR2 FGFR1
12 craniosynostosis 30.0 MSX2 FGFR3 FGFR2 FGFR1 FGF3
13 skeletal dysplasias 29.8 PTH1R NPPC FGFR3 COMP COL2A1
14 turner syndrome 29.8 SHOX IGF1 BGLAP
15 ankylosis 29.8 FGFR2 FGFR1 BGLAP
16 crouzon syndrome 29.7 MSX2 FGFR3 FGFR2 FGFR1 FGF3
17 dysostosis 29.7 MSX2 FGFR3 FGFR2 FGFR1
18 exostosis 29.6 COL2A1 BGLAP ACAN
19 disorders of sexual development 29.6 SOX9 SHOX IGF1
20 spondyloepiphyseal dysplasia with congenital joint dislocations 29.4 FGFR3 COMP COL2A1 ACAN
21 acromesomelic dysplasia 29.4 SHOX NPPC FGFR3 COL2A1
22 tooth agenesis 29.2 MSX2 FGFR2 FGFR1 FGF3
23 thanatophoric dysplasia, type i 29.0 TK1 PTH1R NPPC FGFR3 FGFR2 FGFR1
24 achondrogenesis 29.0 IFT20 COMP COL2A1 ACAN
25 pfeiffer syndrome 28.9 MSX2 FGFR3 FGFR2 FGFR1 COL1A1 BGLAP
26 arthropathy 28.8 IGF1 COMP COL2A1 ACAN
27 brittle bone disorder 28.6 SOX9 PTH1R FGFR3 COL2A1 COL1A1 BGLAP
28 multiple epiphyseal dysplasia 28.4 SOX9 PTH1R FGFR3 COMP COL2A1 ACAN
29 osteoarthritis 28.3 SOX9 IGF1 COMP COL2A1 BGLAP ACAN
30 brachydactyly 28.3 MSX2 FGFR3 COMP COL2A1 ACAN
31 bone disease 27.6 PTH1R IGF1 FGFR3 FGFR2 FGFR1 COMP
32 scoliosis 27.4 SOX9 SHOX IGF1 FGFR3 FGFR2 COMP
33 cleft palate, isolated 27.4 SPRY2 SOX9 MSX2 FGFR3 FGFR2 FGFR1
34 odontochondrodysplasia 26.5 SOX9 SHOX PTH1R NPPC MSX2 IGF1
35 short-limb skeletal dysplasia with severe combined immunodeficiency 12.2
36 dwarfism 11.8
37 rhizomelic chondrodysplasia punctata, type 1 11.7
38 chondrodysplasia punctata 2, x-linked dominant 11.6
39 hydrocephalus, congenital, 1 11.5
40 mesomelia 11.5
41 x-linked chondrodysplasia punctata 1 11.2
42 atelosteogenesis, type i 11.2
43 boomerang dysplasia 11.2
44 sleep apnea 10.5
45 camptodactyly-tall stature-scoliosis-hearing loss syndrome 10.4 NPPC FGFR3
46 eiken syndrome 10.3 SHOX PTH1R
47 hypoparathyroidism 10.3 PTH1R IGF1 BGLAP
48 hemifacial hyperplasia 10.3 FGFR3 FGFR2
49 chondrodysplasia punctata syndrome 10.3
50 hypotonia 10.3

Graphical network of the top 20 diseases related to Achondroplasia:



Diseases related to Achondroplasia

Symptoms & Phenotypes for Achondroplasia

Human phenotypes related to Achondroplasia:

58 31 (show top 50) (show all 57)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 bowing of the legs 58 31 hallmark (90%) Very frequent (99-80%) HP:0002979
2 thoracolumbar kyphosis 58 31 hallmark (90%) Very frequent (99-80%) HP:0005619
3 hearing impairment 58 31 frequent (33%) Frequent (79-30%) HP:0000365
4 depressed nasal bridge 58 31 frequent (33%) Frequent (79-30%) HP:0005280
5 macrocephaly 58 31 frequent (33%) Frequent (79-30%) HP:0000256
6 anteverted nares 58 31 frequent (33%) Frequent (79-30%) HP:0000463
7 frontal bossing 58 31 frequent (33%) Frequent (79-30%) HP:0002007
8 brachydactyly 58 31 frequent (33%) Frequent (79-30%) HP:0001156
9 abnormality of the shape of the midface 58 31 frequent (33%) Frequent (79-30%) HP:0430026
10 obstructive sleep apnea 58 31 frequent (33%) Frequent (79-30%) HP:0002870
11 short long bone 58 31 frequent (33%) Frequent (79-30%) HP:0003026
12 short middle phalanx of finger 58 31 frequent (33%) Frequent (79-30%) HP:0005819
13 limited elbow extension 58 31 frequent (33%) Frequent (79-30%) HP:0001377
14 infantile muscular hypotonia 58 31 frequent (33%) Frequent (79-30%) HP:0008947
15 lumbar hyperlordosis 58 31 frequent (33%) Frequent (79-30%) HP:0002938
16 central sleep apnea 58 31 frequent (33%) Frequent (79-30%) HP:0010536
17 cervical spinal canal stenosis 58 31 frequent (33%) Frequent (79-30%) HP:0008445
18 parietal bossing 58 31 frequent (33%) Frequent (79-30%) HP:0000242
19 short nasal bridge 58 31 frequent (33%) Frequent (79-30%) HP:0003194
20 knee joint hypermobility 58 31 frequent (33%) Frequent (79-30%) HP:0045086
21 hip joint hypermobility 58 31 frequent (33%) Frequent (79-30%) HP:0045087
22 trident hand 58 31 frequent (33%) Frequent (79-30%) HP:0004060
23 short proximal phalanx of finger 58 31 frequent (33%) Frequent (79-30%) HP:0010241
24 functional abnormality of the middle ear 58 31 frequent (33%) Frequent (79-30%) HP:0011452
25 hydrocephalus 58 31 occasional (7.5%) Very rare (<4-1%) HP:0000238
26 restrictive ventilatory defect 58 31 occasional (7.5%) Occasional (29-5%) HP:0002091
27 obesity 58 31 occasional (7.5%) Occasional (29-5%) HP:0001513
28 wide anterior fontanel 58 31 occasional (7.5%) Occasional (29-5%) HP:0000260
29 acanthosis nigricans 58 31 occasional (7.5%) Occasional (29-5%) HP:0000956
30 hypoxemia 58 31 occasional (7.5%) Occasional (29-5%) HP:0012418
31 rhizomelia 58 31 occasional (7.5%) Occasional (29-5%) HP:0008905
32 thoracic hypoplasia 58 31 occasional (7.5%) Occasional (29-5%) HP:0005257
33 abnormality of the wing of the ilium 58 31 occasional (7.5%) Occasional (29-5%) HP:0011867
34 flat acetabular roof 58 31 occasional (7.5%) Occasional (29-5%) HP:0003180
35 narrow greater sciatic notch 31 occasional (7.5%) HP:0003375
36 kyphosis 58 Very frequent (99-80%)
37 recurrent otitis media 31 HP:0000403
38 motor delay 31 HP:0001270
39 conductive hearing impairment 31 HP:0000405
40 spinal canal stenosis 58 Frequent (79-30%)
41 malar flattening 31 HP:0000272
42 genu varum 31 HP:0002970
43 neonatal short-limb short stature 31 HP:0008921
44 midface retrusion 31 HP:0011800
45 disproportionate short stature 58 Very frequent (99-80%)
46 upper airway obstruction 31 HP:0002781
47 brain stem compression 31 HP:0002512
48 limb undergrowth 58 Very frequent (99-80%)
49 short femoral neck 31 HP:0100864
50 generalized joint laxity 31 HP:0002761

Symptoms via clinical synopsis from OMIM:

56
Head And Neck Head:
frontal bossing
megalencephaly

Respiratory Airways:
upper airway obstruction

Skeletal Limbs:
short femoral neck
bowing of legs
rhizomelic shortening
metaphyseal flaring
limited elbow and hip extension

Skeletal Spine:
lumbar kyphosis in infancy
exaggerated lumbar lordosis during childhood and adulthood
congenital spinal stenosis due to short pedicles, especially lumbar
progressive interpediculate narrowing in lumbar spine

Head And Neck Face:
midface hypoplasia

Head And Neck Nose:
low nasal bridge

Skeletal Pelvis:
dysplastic ilium
narrow sacroiliac groove
flat rooted acetabulae

Skeletal Hands:
brachydactyly
trident hand

Neurologic Central Nervous System:
brain stem compression
hydrocephalus, occasional
hypotonia in infancy and early childhood
delayed motor development

Skeletal:
generalized joint laxity

Growth Height:
short-limb dwarfism identifiable at birth
mean male adult height, 131 cm
mean female height, 124 cm

Head And Neck Ears:
recurrent otitis media in infancy and childhood
conductive hearing loss

Skeletal Skull:
jugular bulb dehiscence (in some patients)
foramen magnum stenosis

Clinical features from OMIM:

100800

MGI Mouse Phenotypes related to Achondroplasia:

45 (show all 22)
# Description MGI Source Accession Score Top Affiliating Genes
1 growth/size/body region MP:0005378 10.4 COL1A1 COL2A1 COMP FGF3 FGFR1 FGFR2
2 homeostasis/metabolism MP:0005376 10.4 BGLAP COL1A1 COL2A1 COMP F2RL2 FGFR1
3 cardiovascular system MP:0005385 10.35 COL1A1 COL2A1 COMP FGFR1 FGFR2 IGF1
4 endocrine/exocrine gland MP:0005379 10.35 BGLAP COL1A1 FGFR1 FGFR2 IGF1 MAP2K1
5 mortality/aging MP:0010768 10.35 COL1A1 COL2A1 FGF3 FGFR1 FGFR2 FGFR3
6 cellular MP:0005384 10.34 BGLAP COL1A1 COL2A1 COMP FGFR1 FGFR2
7 craniofacial MP:0005382 10.33 COL1A1 COL2A1 FGFR1 FGFR2 FGFR3 MAP2K1
8 digestive/alimentary MP:0005381 10.32 COL1A1 COL2A1 FGFR1 FGFR2 FGFR3 MAP2K1
9 immune system MP:0005387 10.32 BGLAP COL1A1 COL2A1 COMP FGF3 FGFR1
10 limbs/digits/tail MP:0005371 10.31 COL1A1 COL2A1 COMP FGF3 FGFR1 FGFR2
11 hearing/vestibular/ear MP:0005377 10.29 COL1A1 COL2A1 FGF3 FGFR1 FGFR2 FGFR3
12 hematopoietic system MP:0005397 10.28 BGLAP COL1A1 F2RL2 FGFR1 FGFR2 FGFR3
13 nervous system MP:0003631 10.28 COL1A1 COL2A1 FGF3 FGFR1 FGFR2 FGFR3
14 embryo MP:0005380 10.23 COL1A1 COL2A1 FGF3 FGFR1 FGFR2 MAP2K1
15 normal MP:0002873 10.15 COL1A1 COL2A1 COMP FGF3 FGFR1 FGFR2
16 reproductive system MP:0005389 10.03 BGLAP COL1A1 FGF3 FGFR1 FGFR2 FGFR3
17 neoplasm MP:0002006 10 COL1A1 FGFR2 FGFR3 IGF1 MAP2K1 PTH1R
18 renal/urinary system MP:0005367 9.97 COL1A1 COL2A1 FGFR1 FGFR2 FGFR3 IFT20
19 no phenotypic analysis MP:0003012 9.95 COL1A1 FGF3 FGFR1 FGFR2 FGFR3 IFT20
20 skeleton MP:0005390 9.83 BGLAP COL1A1 COL2A1 COMP FGF3 FGFR1
21 respiratory system MP:0005388 9.81 COL1A1 COL2A1 FGFR2 FGFR3 IGF1 PTH1R
22 vision/eye MP:0005391 9.36 COL1A1 COL2A1 FGFR1 FGFR2 FGFR3 IFT20

Drugs & Therapeutics for Achondroplasia

Drugs for Achondroplasia (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 19)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Simvastatin Approved Phase 3 79902-63-9 54454
2 Natriuretic Peptide, C-Type Phase 3
3 Hypolipidemic Agents Phase 3
4 Lipid Regulating Agents Phase 3
5 Hydroxymethylglutaryl-CoA Reductase Inhibitors Phase 3
6 Anticholesteremic Agents Phase 3
7 Antimetabolites Phase 3
8
mometasone furoate Approved, Investigational, Vet_approved Phase 2 83919-23-7
9
Tyrosine Approved, Investigational, Nutraceutical Phase 2 60-18-4 6057
10
Resveratrol Investigational Phase 2 501-36-0 445154
11 Mitogens Phase 2
12 Analgesics, Non-Narcotic Phase 2
13 Antioxidants Phase 2
14 Analgesics Phase 2
15 Platelet Aggregation Inhibitors Phase 2
16 Protective Agents Phase 2
17 Anti-Inflammatory Agents Phase 2
18 Antirheumatic Agents Phase 2
19 Anti-Inflammatory Agents, Non-Steroidal Phase 2

Interventional clinical trials:

(show all 26)
# 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 Treatment With HMG-COA Reductase Inhibitor (Simvastatin) of Growth and Bone Abnormalities in Children With Noonan Syndrome: A Phase III Randomised, Double Blind, Placebo-controlled Therapeutic Trial Recruiting NCT02713945 Phase 3 Simvastatin;Placebo
3 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
4 A Phase 2, Open-label, Sequential Cohort Dose-escalation Study of BMN 111 in Children With Achondroplasia Completed NCT02055157 Phase 2 BMN 111
5 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
6 Resveratrol Trial for Relief of Pain in Pseudoachondroplasia Recruiting NCT03866200 Phase 2 resveratrol;Placebo
7 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
8 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
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 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 12 Months in Prepubertal Children With Achondroplasia Not yet recruiting NCT04085523 Phase 2 TransCon CNP;Placebo for TransCon CNP
11 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
12 C-Type Natriuretic Peptide and Achondroplasia Completed NCT01541306
13 Specific Survey of Norditropin® in Achondroplasia: Survey for Long-term Application Completed NCT01516229 somatropin
14 Issues Surrounding Prenatal Genetic Testing for Achondroplasia Completed NCT00001536
15 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
16 Clinical and Molecular Manifestations of Human Skeletal Dysplasias and Short Stature Completed NCT00001754
17 ACHieve: A Multi-center, Longitudinal, Observational Study of Children With Achondroplasia Recruiting NCT03875534
18 A Multi-center, Prospective, Longitudinal, Observational Study to Investigate the Clinical and Anthropometric Characteristics of Children With the Diagnosis Achondroplasia. Recruiting NCT03794609
19 Prospective Clinical Assessment Study in Children With Achondroplasia: The PROPEL Trial Recruiting NCT04035811
20 Lifetime Impact Study for Achondroplasia (LISA) Recruiting NCT03872531
21 Universal Haplotype-Based Non Invasive Prenatal Diagnosis by Linked-Read Sequencing (10XGenomics™ Technology) Recruiting NCT03622892
22 The Norwegian Adult Achondroplasia Study Active, not recruiting NCT03780153
23 The Impact of Achondroplasia on Quality of Life, Healthcare Resource Use, Clinical, Socio-economic and Psychosocial State of the Individual. Active, not recruiting NCT03449368
24 A Multicenter, Multinational Clinical Assessment Study for Pediatric Patients With Achondroplasia Enrolling by invitation NCT01603095
25 Achondroplasia Natural History Multicenter Clinical Study Enrolling by invitation NCT02597881
26 Retrospective Clinical Study to Evaluate of Cranio-vertebral Abnormalities Through Radiological Analysis in Patients With Achondroplasia Treated/Followed at the Hôpital Femme Mère Enfant Not yet recruiting NCT04184817

Search NIH Clinical Center for Achondroplasia

Genetic Tests for Achondroplasia

Genetic tests related to Achondroplasia:

# Genetic test Affiliating Genes
1 Achondroplasia 29 FGFR3

Anatomical Context for Achondroplasia

The Foundational Model of Anatomy Ontology organs/tissues related to Achondroplasia:

19
Long Bone

MalaCards organs/tissues related to Achondroplasia:

40
Bone, Spinal Cord, Brain, Testes, Lung, Bone Marrow, Kidney

Publications for Achondroplasia

Articles related to Achondroplasia:

(show top 50) (show all 1696)
# Title Authors PMID Year
1
Mutations in the transmembrane domain of FGFR3 cause the most common genetic form of dwarfism, achondroplasia. 61 56 54 6 24
7913883 1994
2
Germline mosaicism in achondroplasia detected in sperm DNA of the father of three affected sibs. 61 24 6 56
18266238 2008
3
Novel FGFR3 mutations creating cysteine residues in the extracellular domain of the receptor cause achondroplasia or severe forms of hypochondroplasia. 54 61 6 56
16912704 2006
4
Severe complications in a child with achondroplasia and two FGFR3 mutations on the same allele. 6 54 61 56
16411219 2006
5
Acanthosis nigricans in a boy with achondroplasia due to the classical Gly380Arg mutation in FGFR3. 6 56 54 61
15517832 2004
6
A glycine 375-to-cysteine substitution in the transmembrane domain of the fibroblast growth factor receptor-3 in a newborn with achondroplasia. 54 61 6 56
7758520 1995
7
Mutations in the gene encoding fibroblast growth factor receptor-3 in achondroplasia. 54 61 6 56
8078586 1994
8
Germline and somatic mosaicism in achondroplasia. 61 56 6
11186939 2000
9
Achondroplasia with the FGFR3 1138g-->a (G380R) mutation in two sibs sharing a 4p haplotype derived from their unaffected father. 6 56 61
11186940 2000
10
Achondroplasia is defined by recurrent G380R mutations of FGFR3. 54 61 56 24
7847369 1995
11
The population-based prevalence of achondroplasia and thanatophoric dysplasia in selected regions of the US. 24 56 61
18698630 2008
12
Mortality in achondroplasia study: a 42-year follow-up. 24 61 56
17879967 2007
13
Weight for age charts for children with achondroplasia. 61 24 56
17764078 2007
14
Double heterozygosity in bone growth disorders: four new observations and review. 61 56 24
12923858 2003
15
Recurrence risk for sibs of children with "sporadic" achondroplasia. 56 24 61
10678665 2000
16
Distinct patterns of respiratory difficulty in young children with achondroplasia: a clinical, sleep, and lung function study. 24 61 56
9797588 1998
17
Standard weight for height curves in achondroplasia. 56 24 61
8882783 1996
18
Treatment of obstructive sleep apnea in achondroplasia: evaluation of sleep, breathing, and somatosensory-evoked potentials. 61 56 24
8585566 1995
19
Prospective assessment of risks for cervicomedullary-junction compression in infants with achondroplasia. 61 24 56
7887429 1995
20
Obesity in achondroplasia. 56 24 61
3228140 1988
21
Thoracolumbosacral laminectomy in achondroplasia: long-term results in 22 patients. 24 61 56
3425618 1987
22
Mortality in achondroplasia. 61 56 24
3631079 1987
23
Hydrocephalus and achondroplasia. A study of 25 observations. 56 24 61
7438842 1980
24
Standard growth curves for achondroplasia. 61 56 24
690757 1978
25
Achondroplasia. 24 61 56
6023888 1967
26
Novel FGFR3 mutations in exon 7 and implications for expanded screening of achondroplasia and hypochondroplasia: a response to Heuertz et al. 61 6 54
17895900 2008
27
Overexpression of CNP in chondrocytes rescues achondroplasia through a MAPK-dependent pathway. 56 54 61
14702637 2004
28
Fibroblast growth factor receptor-3 as a therapeutic target for Achondroplasia--genetic short limbed dwarfism. 61 54 56
12816345 2003
29
Gly369Cys mutation in mouse FGFR3 causes achondroplasia by affecting both chondrogenesis and osteogenesis. 6 54 61
10587515 1999
30
Compound heterozygosity for the Achondroplasia-hypochondroplasia FGFR3 mutations: prenatal diagnosis and postnatal outcome. 61 54 56
10360393 1999
31
Mutations of the fibroblast growth factor receptor-3 gene in one familial and six sporadic cases of achondroplasia in Japanese patients. 61 54 6
7649548 1995
32
Analysis of the chondroitin sulfate proteoglycan core protein (CSPGCP) gene in achondroplasia and pseudoachondroplasia. 61 54 56
1670752 1991
33
C-Type Natriuretic Peptide Analogue Therapy in Children with Achondroplasia. 56 61
31269546 2019
34
Evaluation of the therapeutic potential of a CNP analog in a Fgfr3 mouse model recapitulating achondroplasia. 56 61
23200862 2012
35
FGFR3 heterodimerization in achondroplasia, the most common form of human dwarfism. 6 61
21324899 2011
36
Physical basis behind achondroplasia, the most common form of human dwarfism. 61 6
20624921 2010
37
Clinical and molecular diagnosis of the skeletal dysplasias associated with mutations in the gene encoding Fibroblast Growth Factor Receptor 3 (FGFR3) in Portugal. 24 54 61
19215249 2009
38
FGFR3 promotes synchondrosis closure and fusion of ossification centers through the MAPK pathway. 61 56
18923003 2009
39
Skeletal dysplasia in ancient Egypt. 61 56
19006207 2008
40
Genetic and other diseases in the pottery of Tumaco-La Tolita culture in Colombia-Ecuador. 61 56
16922718 2006
41
Mosaicism of activating FGFR3 mutations in human skin causes epidermal nevi. 6 61
16841094 2006
42
Advancing age has differential effects on DNA damage, chromatin integrity, gene mutations, and aneuploidies in sperm. 6 61
16766665 2006
43
Dwarfs in ancient Egypt. 61 56
16380966 2006
44
Recent milestones in achondroplasia research. 61 56
16353253 2006
45
Do parents and grandparents of patients with achondroplasia have a higher cancer risk? 56 61
15372518 2004
46
The observed human sperm mutation frequency cannot explain the achondroplasia paternal age effect. 61 56
12397172 2002
47
Absence of correlation between infantile hypotonia and foramen magnum size in achondroplasia. 61 56
11343336 2001
48
Prenatal DNA diagnosis of a single-gene disorder from maternal plasma. 61 6
11030304 2000
49
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. 24 54 61
10696568 2000
50
Abnormal subcortical somatosensory evoked potentials indicate high cervical myelopathy in achondroplasia. 61 56
10445347 1999

Variations for Achondroplasia

ClinVar genetic disease variations for Achondroplasia:

6 (show all 16) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 FGFR3 NM_001163213.1(FGFR3):c.1144G>C (p.Gly382Arg)SNV Pathogenic 16328 rs28931614 4:1806119-1806119 4:1804392-1804392
2 FGFR3 NM_001163213.1(FGFR3):c.742C>T (p.Arg248Cys)SNV Pathogenic 16332 rs121913482 4:1803564-1803564 4:1801837-1801837
3 FGFR3 NM_001163213.1(FGFR3):c.1626C>A (p.Asn542Lys)SNV Pathogenic 16337 rs28933068 4:1807371-1807371 4:1805644-1805644
4 FGFR3 NM_001163213.1(FGFR3):c.1626C>G (p.Asn542Lys)SNV Pathogenic 16338 rs28933068 4:1807371-1807371 4:1805644-1805644
5 FGFR3 NM_001163213.1(FGFR3):c.746C>G (p.Ser249Cys)SNV Pathogenic 16339 rs121913483 4:1803568-1803568 4:1801841-1801841
6 FGFR3 NM_001163213.1(FGFR3):c.835A>T (p.Ser279Cys)SNV Pathogenic 16356 rs121913114 4:1803657-1803657 4:1801930-1801930
7 FGFR3 NM_001163213.1(FGFR3):c.251C>T (p.Ser84Leu)SNV Pathogenic 16358 rs121913116 4:1801122-1801122 4:1799395-1799395
8 FGFR3 NM_001163213.1(FGFR3):c.1955A>C (p.Lys652Thr)SNV Pathogenic 65855 rs121913105 4:1807890-1807890 4:1806163-1806163
9 FGFR3 NM_001163213.1(FGFR3):c.1129G>T (p.Gly377Cys)SNV Pathogenic 16330 rs75790268 4:1806104-1806104 4:1804377-1804377
10 FGFR3 NM_001163213.1(FGFR3):c.749C>G (p.Pro250Arg)SNV Pathogenic/Likely pathogenic 16340 rs4647924 4:1803571-1803571 4:1801844-1801844
11 FGFR3 NM_001163213.1(FGFR3):c.1144G>A (p.Gly382Arg)SNV Conflicting interpretations of pathogenicity 16327 rs28931614 4:1806119-1806119 4:1804392-1804392
12 FGFR3 NM_001163213.1(FGFR3):c.1999G>T (p.Ala667Ser)SNV Uncertain significance 465350 rs764892330 4:1808017-1808017 4:1806290-1806290
13 FGFR3 NM_001163213.1(FGFR3):c.2159A>G (p.Asn720Ser)SNV Uncertain significance 521225 rs139773438 4:1808395-1808395 4:1806668-1806668
14 FGFR3 NM_001163213.1(FGFR3):c.200G>A (p.Gly67Asp)SNV Uncertain significance 546226 rs369232922 4:1801071-1801071 4:1799344-1799344
15 FGFR3 NM_001163213.1(FGFR3):c.1337C>T (p.Ser446Phe)SNV not provided 585087 rs761325047 4:1806615-1806615 4:1804888-1804888
16 FGFR3 NM_001163213.1(FGFR3):c.1136T>G (p.Leu379Arg)SNV no interpretation for the single variant 446185 rs267606809 4:1806111-1806111 4:1804384-1804384

UniProtKB/Swiss-Prot genetic disease variations for Achondroplasia:

73
# Symbol AA change Variation ID SNP ID
1 FGFR3 p.Gly375Cys VAR_004154 rs75790268
2 FGFR3 p.Gly380Arg VAR_004155 rs28931614
3 FGFR3 p.Lys650Met VAR_004161 rs121913105

Expression for Achondroplasia

Search GEO for disease gene expression data for Achondroplasia.

Pathways for Achondroplasia

Pathways related to Achondroplasia according to GeneCards Suite gene sharing:

(show all 42)
# Super pathways Score Top Affiliating Genes
1
Show member pathways
13.79 SOX9 MAP2K1 IGF1 FGFR3 FGFR2 FGFR1
2
Show member pathways
12.95 MAP2K1 IGF1 FGFR3 FGFR2 FGFR1 COL2A1
3
Show member pathways
12.85 MAP2K1 IGF1 COMP COL2A1 COL1A1
4
Show member pathways
12.82 MAP2K1 IGF1 FGFR3 FGFR2 FGFR1
5
Show member pathways
12.81 MAP2K1 IGF1 FGFR3 FGFR2 FGFR1 FGF3
6 12.8 MAP2K1 IGF1 FGFR3 FGFR2 FGFR1 FGF3
7
Show member pathways
12.72 MAP2K1 IGF1 FGFR2 FGFR1 FGF3
8 12.72 MAP2K1 IGF1 FGFR3 FGFR2 FGFR1 FGF3
9
Show member pathways
12.69 MAP2K1 IGF1 FGFR3 FGFR2 FGFR1 FGF3
10
Show member pathways
12.62 SPRY2 MAP2K1 IGF1 FGFR2 FGFR1 FGF3
11 12.61 MAP2K1 FGFR3 FGFR2 FGFR1 FGF3
12
Show member pathways
12.54 SPRY2 FGFR3 FGFR2 FGFR1 FGF3
13
Show member pathways
12.47 MAP2K1 IGF1 FGFR3 FGFR2 FGFR1
14
Show member pathways
12.45 MAP2K1 FGFR3 FGFR2 FGFR1
15
Show member pathways
12.4 MAP2K1 FGFR3 FGFR2 FGFR1
16
Show member pathways
12.36 FGFR3 FGFR2 FGFR1 FGF3
17
Show member pathways
12.36 MAP2K1 IGF1 FGFR3 FGFR2 FGFR1 F2RL2
18
Show member pathways
12.35 FGFR3 FGFR2 FGFR1 FGF3
19
Show member pathways
12.35 MAP2K1 FGFR3 FGFR2 FGFR1 FGF3
20 12.27 MAP2K1 IGF1 FGFR1 COL1A1
21
Show member pathways
12.21 SPRY2 FGFR3 FGFR2 FGFR1 FGF3
22
Show member pathways
12.14 FGFR3 FGFR2 FGFR1 FGF3
23 12.1 SPRY2 FGFR3 FGFR2 FGFR1
24 12.03 MAP2K1 IGF1 FGFR3 FGFR2 FGFR1
25 11.92 PTH1R MAP2K1 FGFR1 BGLAP
26 11.89 MAP2K1 IGF1 COL1A1
27 11.8 FGFR3 FGFR2 FGFR1
28 11.76 SOX9 IGF1 FGFR3 FGFR1
29 11.71 MAP2K1 IGF1 FGFR3 FGFR2 FGFR1
30 11.66 MAP2K1 FGFR3 FGFR2 FGFR1
31 11.64 SOX9 MSX2 FGFR3 FGFR2 FGFR1 COL2A1
32 11.61 IGF1 COL2A1 COL1A1
33 11.47 FGFR3 FGFR2 FGFR1
34 11.41 SPRY2 FGFR2 FGFR1 BGLAP
35 11.41 SOX9 MSX2 IGF1 COL2A1 BGLAP ACAN
36 11.39 PTH1R COL1A1 BGLAP
37 11.36 PTH1R IGF1 COL1A1 BGLAP
38 11.34 COMP COL2A1 ACAN
39 11.29 MAP2K1 FGFR3 FGFR2 FGFR1 FGF3
40 10.98 SOX9 PTH1R IGF1 FGFR3 FGFR1 COL2A1
41 10.87 MAP2K1 IGF1 FGFR3 FGFR2 FGFR1 COL2A1
42 10.82 PTH1R COL1A1 BGLAP

GO Terms for Achondroplasia

Cellular components related to Achondroplasia according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 extracellular matrix GO:0031012 9.56 COMP COL2A1 COL1A1 ACAN
2 receptor complex GO:0043235 9.46 PTH1R FGFR3 FGFR2 FGFR1
3 extracellular region GO:0005576 9.4 NPPC IGF1 FGFR3 FGFR2 FGFR1 FGF3
4 collagen-containing extracellular matrix GO:0062023 9.35 FGFR2 COMP COL2A1 COL1A1 ACAN

Biological processes related to Achondroplasia according to GeneCards Suite gene sharing:

(show top 50) (show all 62)
# Name GO ID Score Top Affiliating Genes
1 multicellular organism development GO:0007275 10.25 SPRY2 SHOX MSX2 FGFR3 FGFR2 FGFR1
2 negative regulation of apoptotic process GO:0043066 10.12 SPRY2 SOX9 MSX2 IGF1 COMP
3 regulation of gene expression GO:0010468 10.06 SOX9 IGF1 FGFR1 COMP COL2A1
4 negative regulation of cell proliferation GO:0008285 10.06 SPRY2 SOX9 PTH1R NPPC MSX2 MAP2K1
5 positive regulation of cell proliferation GO:0008284 10.05 SOX9 PTH1R IGF1 FGFR3 FGFR2 FGFR1
6 negative regulation of gene expression GO:0010629 10.03 SOX9 MAP2K1 IGF1 FGFR1
7 MAPK cascade GO:0000165 10.02 MAP2K1 FGFR3 FGFR2 FGFR1 FGF3
8 positive regulation of ERK1 and ERK2 cascade GO:0070374 10.01 SPRY2 MAP2K1 FGFR3 FGFR2
9 extracellular matrix organization GO:0030198 10 SOX9 COMP COL2A1 COL1A1 ACAN
10 sensory perception of sound GO:0007605 9.95 SPRY2 FGFR1 COL2A1 COL1A1
11 peptidyl-tyrosine phosphorylation GO:0018108 9.94 MAP2K1 FGFR3 FGFR2 FGFR1
12 positive regulation of MAPK cascade GO:0043410 9.93 IGF1 FGFR3 FGFR2 FGFR1
13 positive regulation of protein kinase B signaling GO:0051897 9.93 SPRY2 FGFR3 FGFR2 FGFR1 FGF3
14 lung development GO:0030324 9.9 SPRY2 FGFR2 FGFR1
15 wound healing GO:0042060 9.9 MSX2 FGFR2 COL1A1
16 positive regulation of phosphatidylinositol 3-kinase signaling GO:0014068 9.9 SOX9 IGF1 FGFR1
17 positive regulation of kinase activity GO:0033674 9.89 FGFR3 FGFR2 FGFR1
18 cellular response to retinoic acid GO:0071300 9.88 SOX9 FGFR2 COL1A1
19 cell fate commitment GO:0045165 9.88 SPRY2 SOX9 FGFR2
20 positive regulation of epithelial cell proliferation GO:0050679 9.87 SOX9 IGF1 FGFR2
21 positive regulation of osteoblast differentiation GO:0045669 9.87 NPPC MSX2 IGF1
22 bone development GO:0060348 9.87 FGFR2 COL2A1 BGLAP
23 cellular response to transforming growth factor beta stimulus GO:0071560 9.86 SOX9 FGFR2 COL1A1
24 fibroblast growth factor receptor signaling pathway GO:0008543 9.86 FGFR3 FGFR2 FGFR1 FGF3
25 cartilage development GO:0051216 9.85 SOX9 MSX2 COMP COL2A1
26 regulation of cell differentiation GO:0045595 9.84 SPRY2 SOX9 FGFR1
27 epithelial to mesenchymal transition GO:0001837 9.83 SOX9 FGFR2 FGFR1
28 inner ear morphogenesis GO:0042472 9.83 SPRY2 FGFR2 FGFR1 COL2A1
29 odontogenesis GO:0042476 9.81 MSX2 FGFR2 BGLAP
30 ERK1 and ERK2 cascade GO:0070371 9.8 SOX9 MAP2K1 IGF1
31 endochondral ossification GO:0001958 9.79 FGFR3 COL2A1 COL1A1
32 collagen fibril organization GO:0030199 9.78 COMP COL2A1 COL1A1 ACAN
33 positive regulation of mesenchymal cell proliferation GO:0002053 9.77 SOX9 FGFR2 FGFR1
34 cartilage condensation GO:0001502 9.75 SOX9 COL2A1 ACAN
35 osteoblast development GO:0002076 9.74 PTH1R MSX2 BGLAP
36 skeletal system morphogenesis GO:0048705 9.73 FGFR2 FGFR1 COL2A1 COL1A1
37 branching involved in salivary gland morphogenesis GO:0060445 9.72 FGFR2 FGFR1
38 chondrocyte proliferation GO:0035988 9.72 FGFR3 COMP
39 notochord development GO:0030903 9.72 SOX9 COL2A1
40 mesenchymal cell differentiation GO:0048762 9.72 FGFR2 FGFR1
41 chondrocyte differentiation GO:0002062 9.72 SOX9 PTH1R FGFR3 FGFR1 COL2A1
42 lung-associated mesenchyme development GO:0060484 9.71 FGFR2 FGFR1
43 bone morphogenesis GO:0060349 9.71 MSX2 FGFR3 FGFR2 COMP
44 otic vesicle development GO:0071599 9.7 SOX9 COL2A1
45 bone trabecula formation GO:0060346 9.7 MSX2 COL1A1
46 bud elongation involved in lung branching GO:0060449 9.68 SPRY2 FGFR2
47 lacrimal gland development GO:0032808 9.68 SOX9 FGFR2
48 otic vesicle formation GO:0030916 9.68 SOX9 FGFR2
49 cartilage development involved in endochondral bone morphogenesis GO:0060351 9.68 COL2A1 COL1A1
50 positive regulation of chondrocyte proliferation GO:1902732 9.67 SOX9 COMP

Molecular functions related to Achondroplasia according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 protein binding GO:0005515 10.32 TK1 SPRY2 SOX9 SHOX PTH1R MSX2
2 extracellular matrix structural constituent GO:0005201 9.56 COMP COL2A1 COL1A1 ACAN
3 transmembrane receptor protein tyrosine kinase activity GO:0004714 9.5 FGFR3 FGFR2 FGFR1
4 protein tyrosine kinase activity GO:0004713 9.46 MAP2K1 FGFR3 FGFR2 FGFR1
5 proteoglycan binding GO:0043394 9.43 COMP COL2A1
6 platelet-derived growth factor binding GO:0048407 9.4 COL2A1 COL1A1
7 fibroblast growth factor binding GO:0017134 9.13 FGFR3 FGFR2 FGFR1
8 fibroblast growth factor-activated receptor activity GO:0005007 8.8 FGFR3 FGFR2 FGFR1

Sources for Achondroplasia

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
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
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
53 NINDS
54 Novoseek
56 OMIM
57 OMIM via Orphanet
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
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