ACH
MCID: ACH004
MIFTS: 65

Achondroplasia (ACH)

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

Aliases & Classifications for Achondroplasia

MalaCards integrated aliases for Achondroplasia:

Name: Achondroplasia 57 12 73 25 20 43 58 72 36 29 13 54 6 15 39 70 32
Ach 57 20 43 72
Achondroplastic Dwarfism 20 43 70
Achondroplastic Physique 12
Osteosclerosis Congenita 12
Dwarf, Achondroplastic 43
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®:

57 (Updated 20-May-2021)
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:

25
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® 57 100800
KEGG 36 H01749
MeSH 44 D000130
NCIt 50 C34345
SNOMED-CT 67 268273004
ICD10 32 Q77.4
MESH via Orphanet 45 D000130
ICD10 via Orphanet 33 Q77.4
UMLS via Orphanet 71 C0001080
Orphanet 58 ORPHA15
MedGen 41 C0001080
UMLS 70 C0001080 C2930793

Summaries for Achondroplasia

MedlinePlus Genetics : 43 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 hypochondroplasia. An important gene associated with Achondroplasia is FGFR3 (Fibroblast Growth Factor Receptor 3), and among its related pathways/superpathways are ERK Signaling and TGF-Beta Pathway. The drugs Natriuretic Peptide, C-Type and mometasone furoate 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.

GARD : 20 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® : 57 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) (Updated 20-May-2021)

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 : 72 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 : 73 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 345)
# Related Disease Score Top Affiliating Genes
1 achondroplasia, severe, with developmental delay and acanthosis nigricans 32.8 NPPC FGFR3 FGFR2 FGFR1
2 hypochondroplasia 31.0 TK1 SHOX NPPC FGFR3 FGFR2 FGFR1
3 pseudoachondroplasia 30.9 COMP COL2A1 ACAN
4 spinal stenosis 30.8 COL2A1 COL1A1 ACAN
5 acanthosis nigricans 30.6 IGF1 FGFR3 FGFR2
6 nevus, epidermal 30.4 FGFR3 FGFR2 FGFR1
7 craniosynostosis 30.3 MSX2 FGFR3 FGFR2 FGFR1
8 plagiocephaly 30.0 FGFR3 FGFR2 FGFR1
9 acromesomelic dysplasia, maroteaux type 30.0 SHOX NPPC FGFR3
10 camptodactyly-tall stature-scoliosis-hearing loss syndrome 30.0 NPPC FGFR3
11 synostosis 30.0 MSX2 FGFR3 FGFR2 FGFR1
12 thanatophoric dysplasia, type i 29.9 TK1 PTH1R NPPC FGFR3 FGFR2 FGFR1
13 exostosis 29.7 COL2A1 BGLAP ACAN
14 crouzon syndrome 29.7 MSX2 FGFR3 FGFR2 FGFR1 FGF3
15 dysostosis 29.7 MSX2 FGFR3 FGFR2 FGFR1
16 lacrimoauriculodentodigital syndrome 29.6 FGFR3 FGFR2 FGFR1 FGF3
17 ankylosis 29.6 FGFR2 FGFR1 BGLAP
18 disorder of sexual development 29.5 SOX9 SHOX IGF1
19 spondyloepiphyseal dysplasia with congenital joint dislocations 29.5 FGFR3 COMP COL2A1 ACAN
20 acromesomelic dysplasia 29.5 SHOX NPPC FGFR3 COL2A1
21 muenke syndrome 29.4 MSX2 FGFR3 FGFR2 FGFR1
22 tooth agenesis 29.2 MSX2 FGFR2 FGFR1 FGF3
23 multiple epiphyseal dysplasia 29.0 COMP COL2A1 ACAN
24 achondrogenesis 29.0 IFT20 FGFR3 COMP COL2A1 ACAN
25 pfeiffer syndrome 28.9 MSX2 FGFR3 FGFR2 FGFR1 COL1A1 BGLAP
26 arthropathy 28.9 IGF1 COMP COL2A1 ACAN
27 osteoarthritis 28.8 SOX9 COMP COL2A1 BGLAP ACAN
28 brachydactyly 28.6 MSX2 FGFR3 COMP COL2A1 ACAN
29 cleft palate, isolated 28.3 SOX9 MSX2 FGFR3 FGFR2 FGFR1 FGF3
30 bone disease 28.1 PTH1R IGF1 FGFR3 FGFR2 FGFR1 COMP
31 scoliosis 28.0 SOX9 SHOX IGF1 FGFR3 FGFR2 COMP
32 osteochondrodysplasia 28.0 SOX9 SHOX PTH1R NPPC MSX2 IGF1
33 brittle bone disorder 27.7 SOX9 PTH1R MSX2 IGF1 FGFR3 COMP
34 short-limb skeletal dysplasia with severe combined immunodeficiency 11.6
35 dwarfism 11.3
36 rhizomelic chondrodysplasia punctata, type 1 11.2
37 chondrodysplasia punctata 2, x-linked dominant 11.0
38 x-linked chondrodysplasia punctata 1 10.9
39 mesomelia 10.9
40 atelosteogenesis, type i 10.9
41 boomerang dysplasia 10.9
42 hydrocephalus, congenital, 1 10.9
43 hydrocephalus 10.5
44 sleep apnea 10.4
45 eiken syndrome 10.3 SHOX PTH1R
46 epicondylitis 10.2 COL1A1 ACAN
47 hemifacial hyperplasia 10.2 FGFR3 FGFR2
48 hypoparathyroidism 10.2 PTH1R IGF1 BGLAP
49 parathyroid gland disease 10.2 PTH1R FGF3 BGLAP
50 craniosynostosis 1 10.2

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 macrocephaly 58 31 frequent (33%) Frequent (79-30%) HP:0000256
4 frontal bossing 58 31 frequent (33%) Frequent (79-30%) HP:0002007
5 hearing impairment 58 31 frequent (33%) Frequent (79-30%) HP:0000365
6 depressed nasal bridge 58 31 frequent (33%) Frequent (79-30%) HP:0005280
7 anteverted nares 58 31 frequent (33%) Frequent (79-30%) HP:0000463
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 obesity 58 31 occasional (7.5%) Occasional (29-5%) HP:0001513
27 wide anterior fontanel 58 31 occasional (7.5%) Occasional (29-5%) HP:0000260
28 acanthosis nigricans 58 31 occasional (7.5%) Occasional (29-5%) HP:0000956
29 hypoxemia 58 31 occasional (7.5%) Occasional (29-5%) HP:0012418
30 rhizomelia 58 31 occasional (7.5%) Occasional (29-5%) HP:0008905
31 thoracic hypoplasia 58 31 occasional (7.5%) Occasional (29-5%) HP:0005257
32 restrictive ventilatory defect 58 31 occasional (7.5%) Occasional (29-5%) HP:0002091
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 megalencephaly 31 HP:0001355
37 kyphosis 58 Very frequent (99-80%)
38 recurrent otitis media 31 HP:0000403
39 motor delay 31 HP:0001270
40 conductive hearing impairment 31 HP:0000405
41 spinal canal stenosis 58 Frequent (79-30%)
42 malar flattening 31 HP:0000272
43 genu varum 31 HP:0002970
44 neonatal short-limb short stature 31 HP:0008921
45 midface retrusion 31 HP:0011800
46 disproportionate short stature 58 Very frequent (99-80%)
47 upper airway obstruction 31 HP:0002781
48 brain stem compression 31 HP:0002512
49 limb undergrowth 58 Very frequent (99-80%)
50 short femoral neck 31 HP:0100864

Symptoms via clinical synopsis from OMIM®:

57 (Updated 20-May-2021)
Head And Neck Head:
megalencephaly
frontal bossing

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 (Updated 20-May-2021)

MGI Mouse Phenotypes related to Achondroplasia:

46 (show all 21)
# Description MGI Source Accession Score Top Affiliating Genes
1 homeostasis/metabolism MP:0005376 10.39 BGLAP COL1A1 COL2A1 COMP F2RL2 FGFR1
2 growth/size/body region MP:0005378 10.36 COL1A1 COL2A1 COMP FGF3 FGFR1 FGFR2
3 cardiovascular system MP:0005385 10.34 COL1A1 COL2A1 COMP FGFR1 FGFR2 IGF1
4 cellular MP:0005384 10.33 BGLAP COL1A1 COL2A1 COMP FGFR1 FGFR2
5 immune system MP:0005387 10.31 BGLAP COL1A1 COL2A1 COMP FGF3 FGFR1
6 endocrine/exocrine gland MP:0005379 10.3 BGLAP COL1A1 FGFR1 FGFR2 IGF1 MAP2K1
7 hematopoietic system MP:0005397 10.3 BGLAP COL1A1 F2RL2 FGF3 FGFR1 FGFR2
8 mortality/aging MP:0010768 10.3 COL1A1 COL2A1 FGF3 FGFR1 FGFR2 FGFR3
9 craniofacial MP:0005382 10.28 COL1A1 COL2A1 FGFR1 FGFR2 FGFR3 MAP2K1
10 digestive/alimentary MP:0005381 10.27 COL1A1 COL2A1 FGFR1 FGFR2 FGFR3 MAP2K1
11 limbs/digits/tail MP:0005371 10.26 COL1A1 COL2A1 COMP FGF3 FGFR1 FGFR2
12 nervous system MP:0003631 10.25 COL1A1 COL2A1 FGF3 FGFR1 FGFR2 FGFR3
13 hearing/vestibular/ear MP:0005377 10.24 COL1A1 COL2A1 FGF3 FGFR1 FGFR2 FGFR3
14 embryo MP:0005380 10.22 COL1A1 COL2A1 FGF3 FGFR1 FGFR2 MAP2K1
15 normal MP:0002873 10.15 COL1A1 COL2A1 COMP FGF3 FGFR1 FGFR2
16 reproductive system MP:0005389 10 BGLAP COL1A1 FGF3 FGFR1 FGFR2 FGFR3
17 renal/urinary system MP:0005367 9.97 COL1A1 COL2A1 FGFR1 FGFR2 FGFR3 IFT20
18 no phenotypic analysis MP:0003012 9.95 COL1A1 FGF3 FGFR1 FGFR2 FGFR3 IFT20
19 skeleton MP:0005390 9.8 BGLAP COL1A1 COL2A1 COMP FGF3 FGFR1
20 respiratory system MP:0005388 9.76 COL1A1 COL2A1 FGFR2 FGFR3 IGF1 PTH1R
21 vision/eye MP:0005391 9.36 COL1A1 COL2A1 FGF3 FGFR1 FGFR2 FGFR3

Drugs & Therapeutics for Achondroplasia

Drugs for Achondroplasia (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 Antirheumatic Agents Phase 2
7 Antioxidants Phase 2
8 Anti-Inflammatory Agents, Non-Steroidal Phase 2
9 Analgesics Phase 2
10 Protective Agents Phase 2
11 Anti-Inflammatory Agents Phase 2
12 Platelet Aggregation Inhibitors Phase 2
13 Analgesics, Non-Narcotic 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 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
5 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
6 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
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 The Impact of Achondroplasia on Quality of Life, Healthcare Resource Use, Clinical, Socio-economic and Psychosocial State of the Individual. Completed NCT03449368
15 Issues Surrounding Prenatal Genetic Testing for Achondroplasia Completed NCT00001536
16 Lifetime Impact Study for Achondroplasia (LISA) Completed NCT03872531
17 Specific Survey of Norditropin® in Achondroplasia: Survey for Long-term Application Completed NCT01516229 somatropin
18 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
19 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
20 A Multi-center, Prospective, Longitudinal, Observational Study to Investigate the Clinical and Anthropometric Characteristics of Children With the Diagnosis Achondroplasia. Recruiting NCT03794609
21 ACHieve: A Multi-center, Longitudinal, Observational Study of Children With Achondroplasia Recruiting NCT03875534
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

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, Kidney, Heart, Myeloid, Lung

Publications for Achondroplasia

Articles related to Achondroplasia:

(show top 50) (show all 1764)
# Title Authors PMID Year
1
Mutations in the transmembrane domain of FGFR3 cause the most common genetic form of dwarfism, achondroplasia. 6 25 57 54 61
7913883 1994
2
Germline mosaicism in achondroplasia detected in sperm DNA of the father of three affected sibs. 61 57 25 6
18266238 2008
3
Novel FGFR3 mutations creating cysteine residues in the extracellular domain of the receptor cause achondroplasia or severe forms of hypochondroplasia. 61 54 6 57
16912704 2006
4
Severe complications in a child with achondroplasia and two FGFR3 mutations on the same allele. 54 61 6 57
16411219 2006
5
Acanthosis nigricans in a boy with achondroplasia due to the classical Gly380Arg mutation in FGFR3. 57 6 61 54
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 6 57 61
7758520 1995
7
Mutations in the gene encoding fibroblast growth factor receptor-3 in achondroplasia. 61 54 6 57
8078586 1994
8
Germline and somatic mosaicism in achondroplasia. 6 57 61
11186939 2000
9
Achondroplasia with the FGFR3 1138g-->a (G380R) mutation in two sibs sharing a 4p haplotype derived from their unaffected father. 61 6 57
11186940 2000
10
Achondroplasia is defined by recurrent G380R mutations of FGFR3. 54 57 25 61
7847369 1995
11
C-Type Natriuretic Peptide Analogue Therapy in Children with Achondroplasia. 25 57 61
31269546 2019
12
The population-based prevalence of achondroplasia and thanatophoric dysplasia in selected regions of the US. 61 25 57
18698630 2008
13
Mortality in achondroplasia study: a 42-year follow-up. 61 57 25
17879967 2007
14
Weight for age charts for children with achondroplasia. 57 25 61
17764078 2007
15
Double heterozygosity in bone growth disorders: four new observations and review. 61 57 25
12923858 2003
16
Recurrence risk for sibs of children with "sporadic" achondroplasia. 61 57 25
10678665 2000
17
Distinct patterns of respiratory difficulty in young children with achondroplasia: a clinical, sleep, and lung function study. 61 57 25
9797588 1998
18
Standard weight for height curves in achondroplasia. 61 57 25
8882783 1996
19
Treatment of obstructive sleep apnea in achondroplasia: evaluation of sleep, breathing, and somatosensory-evoked potentials. 61 25 57
8585566 1995
20
Prospective assessment of risks for cervicomedullary-junction compression in infants with achondroplasia. 25 57 61
7887429 1995
21
Obesity in achondroplasia. 25 57 61
3228140 1988
22
Thoracolumbosacral laminectomy in achondroplasia: long-term results in 22 patients. 25 57 61
3425618 1987
23
Mortality in achondroplasia. 57 25 61
3631079 1987
24
Hydrocephalus and achondroplasia. A study of 25 observations. 61 25 57
7438842 1980
25
Standard growth curves for achondroplasia. 61 57 25
690757 1978
26
Achondroplasia. 61 57 25
6023888 1967
27
Novel FGFR3 mutations in exon 7 and implications for expanded screening of achondroplasia and hypochondroplasia: a response to Heuertz et al. 6 61 54
17895900 2008
28
Overexpression of CNP in chondrocytes rescues achondroplasia through a MAPK-dependent pathway. 61 54 57
14702637 2004
29
Fibroblast growth factor receptor-3 as a therapeutic target for Achondroplasia--genetic short limbed dwarfism. 54 61 57
12816345 2003
30
Gly369Cys mutation in mouse FGFR3 causes achondroplasia by affecting both chondrogenesis and osteogenesis. 6 61 54
10587515 1999
31
Compound heterozygosity for the Achondroplasia-hypochondroplasia FGFR3 mutations: prenatal diagnosis and postnatal outcome. 61 57 54
10360393 1999
32
Mutations of the fibroblast growth factor receptor-3 gene in one familial and six sporadic cases of achondroplasia in Japanese patients. 54 6 61
7649548 1995
33
Analysis of the chondroitin sulfate proteoglycan core protein (CSPGCP) gene in achondroplasia and pseudoachondroplasia. 54 61 57
1670752 1991
34
Evaluation of the therapeutic potential of a CNP analog in a Fgfr3 mouse model recapitulating achondroplasia. 61 57
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. 25 54 61
19215249 2009
38
FGFR3 promotes synchondrosis closure and fusion of ossification centers through the MAPK pathway. 61 57
18923003 2009
39
Skeletal dysplasia in ancient Egypt. 61 57
19006207 2008
40
Genetic and other diseases in the pottery of Tumaco-La Tolita culture in Colombia-Ecuador. 61 57
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. 61 6
16766665 2006
43
Dwarfs in ancient Egypt. 57 61
16380966 2006
44
Recent milestones in achondroplasia research. 61 57
16353253 2006
45
Do parents and grandparents of patients with achondroplasia have a higher cancer risk? 61 57
15372518 2004
46
The observed human sperm mutation frequency cannot explain the achondroplasia paternal age effect. 61 57
12397172 2002
47
Absence of correlation between infantile hypotonia and foramen magnum size in achondroplasia. 61 57
11343336 2001
48
Prenatal DNA diagnosis of a single-gene disorder from maternal plasma. 6 61
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. 54 61 25
10696568 2000
50
Abnormal subcortical somatosensory evoked potentials indicate high cervical myelopathy in achondroplasia. 57 61
10445347 1999

Variations for Achondroplasia

ClinVar genetic disease variations for Achondroplasia:

6 (show all 22)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 FGFR3 NM_000142.5(FGFR3):c.251C>T (p.Ser84Leu) SNV Pathogenic 16358 rs121913116 GRCh37: 4:1801122-1801122
GRCh38: 4:1799395-1799395
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_001163213.1(FGFR3):c.746C>G (p.Ser249Cys) SNV Pathogenic 16339 rs121913483 GRCh37: 4:1803568-1803568
GRCh38: 4:1801841-1801841
4 FGFR3 NM_000142.5(FGFR3):c.835A>T (p.Ser279Cys) SNV Pathogenic 16356 rs121913114 GRCh37: 4:1803657-1803657
GRCh38: 4:1801930-1801930
5 FGFR3 NM_000142.5(FGFR3):c.1138G>C (p.Gly380Arg) SNV Pathogenic 16328 rs28931614 GRCh37: 4:1806119-1806119
GRCh38: 4:1804392-1804392
6 FGFR3 NM_000142.5(FGFR3):c.1620C>A (p.Asn540Lys) SNV Pathogenic 16337 rs28933068 GRCh37: 4:1807371-1807371
GRCh38: 4:1805644-1805644
7 FGFR3 NM_000142.5(FGFR3):c.1138G>A SNV Pathogenic 441276 rs28931614 GRCh37: 4:1806119-1806119
GRCh38: 4:1804392-1804392
8 FGFR3 NM_000142.5(FGFR3):c.1123G>T (p.Gly375Cys) SNV Pathogenic 16330 rs75790268 GRCh37: 4:1806104-1806104
GRCh38: 4:1804377-1804377
9 FGFR3 NM_000142.5(FGFR3):c.251C>T (p.Ser84Leu) SNV Pathogenic 16358 rs121913116 GRCh37: 4:1801122-1801122
GRCh38: 4:1799395-1799395
10 FGFR3 NM_000142.5(FGFR3):c.749C>G (p.Pro250Arg) SNV Pathogenic 16340 rs4647924 GRCh37: 4:1803571-1803571
GRCh38: 4:1801844-1801844
11 FGFR3 NM_000142.5(FGFR3):c.1620C>G (p.Asn540Lys) SNV Pathogenic 16338 rs28933068 GRCh37: 4:1807371-1807371
GRCh38: 4:1805644-1805644
12 FGFR3 NM_000142.5(FGFR3):c.1620C>G (p.Asn540Lys) SNV Pathogenic 16338 rs28933068 GRCh37: 4:1807371-1807371
GRCh38: 4:1805644-1805644
13 FGFR3 NM_000142.5(FGFR3):c.1138G>A SNV Pathogenic 16327 rs28931614 GRCh37: 4:1806119-1806119
GRCh38: 4:1804392-1804392
14 FGFR3 NM_000142.5(FGFR3):c.749C>G (p.Pro250Arg) SNV Pathogenic 16340 rs4647924 GRCh37: 4:1803571-1803571
GRCh38: 4:1801844-1801844
15 FGFR3 NM_000142.5(FGFR3):c.742C>T (p.Arg248Cys) SNV Pathogenic 16332 rs121913482 GRCh37: 4:1803564-1803564
GRCh38: 4:1801837-1801837
16 FGFR3 NM_000142.5(FGFR3):c.1138G>A SNV Conflicting interpretations of pathogenicity 16327 rs28931614 GRCh37: 4:1806119-1806119
GRCh38: 4:1804392-1804392
17 FGFR3 NM_000142.5(FGFR3):c.1606A>G (p.Lys536Glu) SNV Uncertain significance 976434 GRCh37: 4:1807357-1807357
GRCh38: 4:1805630-1805630
18 FGFR3 NM_000142.5(FGFR3):c.2153A>G (p.Asn718Ser) SNV Uncertain significance 521225 rs139773438 GRCh37: 4:1808395-1808395
GRCh38: 4:1806668-1806668
19 FGFR3 NM_000142.5(FGFR3):c.1993G>T (p.Ala665Ser) SNV Uncertain significance 465350 rs764892330 GRCh37: 4:1808017-1808017
GRCh38: 4:1806290-1806290
20 FGFR3 NM_000142.5(FGFR3):c.200G>A (p.Gly67Asp) SNV Uncertain significance 546226 rs369232922 GRCh37: 4:1801071-1801071
GRCh38: 4:1799344-1799344
21 FGFR3 NM_000142.4(FGFR3):c.616-6G>A SNV Uncertain significance 255344 rs17883400 GRCh37: 4:1803341-1803341
GRCh38: 4:1801614-1801614
22 FGFR3 NM_000142.5(FGFR3):c.1331C>T (p.Ser444Phe) SNV not provided 585087 rs761325047 GRCh37: 4:1806615-1806615
GRCh38: 4:1804888-1804888

UniProtKB/Swiss-Prot genetic disease variations for Achondroplasia:

72
# 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 43)
# Super pathways Score Top Affiliating Genes
1
Show member pathways
13.77 SOX9 MAP2K1 IGF1 FGFR3 FGFR2 FGFR1
2
Show member pathways
13.5 MAP2K1 IGF1 FGFR3 FGFR2 FGFR1 FGF3
3
Show member pathways
12.93 MAP2K1 IGF1 FGFR3 FGFR2 FGFR1 COL2A1
4
Show member pathways
12.86 MAP2K1 IGF1 FGFR3 FGFR2 FGFR1 FGF3
5
Show member pathways
12.85 MAP2K1 IGF1 COMP COL2A1 COL1A1
6
Show member pathways
12.82 MAP2K1 IGF1 FGFR3 FGFR2 FGFR1
7 12.78 MAP2K1 IGF1 FGFR3 FGFR2 FGFR1 FGF3
8
Show member pathways
12.72 MAP2K1 IGF1 FGFR2 FGFR1 FGF3
9 12.69 MAP2K1 IGF1 FGFR3 FGFR2 FGFR1 FGF3
10
Show member pathways
12.66 MAP2K1 IGF1 FGFR3 FGFR2 FGFR1 FGF3
11
Show member pathways
12.64 MAP2K1 IGF1 FGFR2 FGFR1 FGF3
12 12.6 MAP2K1 FGFR3 FGFR2 FGFR1 FGF3
13
Show member pathways
12.45 MAP2K1 IGF1 FGFR3 FGFR2
14
Show member pathways
12.45 MAP2K1 IGF1 FGFR3 FGFR2 FGFR1
15
Show member pathways
12.4 MAP2K1 FGFR3 FGFR2 FGFR1
16
Show member pathways
12.37 FGFR3 FGFR2 FGFR1 FGF3
17
Show member pathways
12.35 FGFR3 FGFR2 FGFR1 FGF3
18 12.35 FGFR3 FGFR2 FGFR1 FGF3
19
Show member pathways
12.33 MAP2K1 IGF1 FGFR3 FGFR2 FGFR1 F2RL2
20
Show member pathways
12.32 MAP2K1 FGFR3 FGFR2 FGFR1 FGF3
21
Show member pathways
12.31 MAP2K1 FGFR3 FGFR2 FGFR1
22 12.26 MAP2K1 IGF1 FGFR1 COL1A1
23
Show member pathways
12.23 FGFR3 FGFR2 FGFR1 FGF3
24
Show member pathways
12.12 FGFR3 FGFR2 FGFR1 FGF3
25 12.01 MAP2K1 IGF1 FGFR3 FGFR2 FGFR1
26 11.89 MAP2K1 IGF1 COL1A1
27 11.89 PTH1R MAP2K1 FGFR1 BGLAP
28 11.8 FGFR3 FGFR2 FGFR1
29 11.74 SOX9 MSX2 FGFR3 FGFR2 FGFR1 COL2A1
30 11.72 SOX9 IGF1 FGFR3 FGFR1
31 11.69 MAP2K1 IGF1 FGFR3 FGFR2 FGFR1
32 11.64 MAP2K1 FGFR3 FGFR2 FGFR1
33 11.61 IGF1 COL2A1 COL1A1
34 11.48 FGFR2 FGFR1 BGLAP
35 11.45 FGFR3 FGFR2 FGFR1
36 11.41 SOX9 MSX2 IGF1 COL2A1 BGLAP ACAN
37 11.38 PTH1R COL1A1 BGLAP
38 11.36 PTH1R IGF1 COL1A1 BGLAP
39 11.35 MAP2K1 FGFR3 FGFR2 FGFR1 FGF3
40 11.32 COMP COL2A1 ACAN
41 10.98 SOX9 PTH1R IGF1 FGFR3 FGFR1 COL2A1
42 10.8 PTH1R COL1A1 BGLAP
43 10.71 MAP2K1 IGF1 FGFR3 FGFR2 FGFR1 COL2A1

GO Terms for Achondroplasia

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

# Name GO ID Score Top Affiliating Genes
1 extracellular space GO:0005615 9.86 NPPC IGF1 FGF3 COMP COL2A1 COL1A1
2 extracellular matrix GO:0031012 9.62 COMP COL2A1 COL1A1 ACAN
3 receptor complex GO:0043235 9.46 PTH1R FGFR3 FGFR2 FGFR1
4 extracellular region GO:0005576 9.44 NPPC IGF1 FGFR3 FGFR2 FGFR1 FGF3
5 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 all 41)
# Name GO ID Score Top Affiliating Genes
1 multicellular organism development GO:0007275 10.2 BMP8B FGF3 FGFR1 FGFR2 FGFR3 MSX2
2 positive regulation of cell proliferation GO:0008284 10.02 SOX9 PTH1R IGF1 FGFR3 FGFR2 FGFR1
3 MAPK cascade GO:0000165 9.97 MAP2K1 FGFR3 FGFR2 FGFR1 FGF3
4 extracellular matrix organization GO:0030198 9.95 SOX9 COMP COL2A1 COL1A1 ACAN
5 positive regulation of protein kinase B signaling GO:0051897 9.93 FGFR3 FGFR2 FGFR1 FGF3
6 peptidyl-tyrosine phosphorylation GO:0018108 9.9 MAP2K1 FGFR3 FGFR2 FGFR1
7 positive regulation of MAPK cascade GO:0043410 9.88 IGF1 FGFR3 FGFR2 FGFR1
8 osteoblast differentiation GO:0001649 9.86 MSX2 COL1A1 BGLAP
9 wound healing GO:0042060 9.86 IGF1 FGFR2 COL1A1
10 positive regulation of phosphatidylinositol 3-kinase signaling GO:0014068 9.85 SOX9 IGF1 FGFR1
11 positive regulation of kinase activity GO:0033674 9.85 FGFR3 FGFR2 FGFR1
12 cellular response to retinoic acid GO:0071300 9.84 SOX9 FGFR2 COL1A1
13 positive regulation of epithelial cell proliferation GO:0050679 9.84 SOX9 IGF1 FGFR2
14 cellular response to transforming growth factor beta stimulus GO:0071560 9.81 SOX9 FGFR2 COL1A1
15 bone development GO:0060348 9.81 FGFR2 COL2A1 BGLAP
16 fibroblast growth factor receptor signaling pathway GO:0008543 9.81 FGFR3 FGFR2 FGFR1 FGF3
17 cartilage development GO:0051216 9.8 SOX9 COMP COL2A1 BMP8B
18 epithelial to mesenchymal transition GO:0001837 9.79 SOX9 FGFR2 FGFR1
19 bone morphogenesis GO:0060349 9.77 FGFR3 FGFR2 COMP
20 ERK1 and ERK2 cascade GO:0070371 9.75 SOX9 MAP2K1 IGF1
21 endochondral ossification GO:0001958 9.73 FGFR3 COL2A1 COL1A1
22 collagen fibril organization GO:0030199 9.73 COMP COL2A1 COL1A1 ACAN
23 cartilage condensation GO:0001502 9.71 SOX9 COL2A1 ACAN
24 chondrocyte development GO:0002063 9.7 SOX9 COMP ACAN
25 chondrocyte proliferation GO:0035988 9.68 FGFR3 COMP
26 notochord development GO:0030903 9.67 COL2A1 SOX9
27 cartilage development involved in endochondral bone morphogenesis GO:0060351 9.65 COL1A1 COL2A1
28 otic vesicle development GO:0071599 9.65 SOX9 COL2A1
29 lacrimal gland development GO:0032808 9.65 SOX9 FGFR2
30 otic vesicle formation GO:0030916 9.64 SOX9 FGFR2
31 limb bud formation GO:0060174 9.63 SOX9 FGFR2 COL2A1
32 positive regulation of chondrocyte proliferation GO:1902732 9.62 SOX9 COMP
33 chondrocyte differentiation GO:0002062 9.62 SOX9 PTH1R FGFR3 COL2A1
34 anterior head development GO:0097065 9.61 SOX9 COL2A1
35 prostate gland morphogenesis GO:0060512 9.61 SOX9 FGFR2
36 ossification GO:0001503 9.61 SOX9 PTH1R NPPC MSX2 COMP COL2A1
37 positive regulation of phospholipase activity GO:0010518 9.58 FGFR3 FGFR2 FGFR1
38 skeletal system morphogenesis GO:0048705 9.56 FGFR2 FGFR1 COL2A1 COL1A1
39 bone mineralization GO:0030282 9.55 PTH1R FGFR3 FGFR2 COMP BGLAP
40 endochondral bone growth GO:0003416 9.54 FGFR3 FGFR2 COMP
41 skeletal system development GO:0001501 9.4 SOX9 SHOX PTH1R IGF1 FGFR3 FGFR1

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

# Name GO ID Score Top Affiliating Genes
1 extracellular matrix structural constituent GO:0005201 9.56 COMP COL2A1 COL1A1 ACAN
2 transmembrane receptor protein tyrosine kinase activity GO:0004714 9.5 FGFR3 FGFR2 FGFR1
3 protein tyrosine kinase activity GO:0004713 9.46 MAP2K1 FGFR3 FGFR2 FGFR1
4 proteoglycan binding GO:0043394 9.4 COMP COL2A1
5 platelet-derived growth factor binding GO:0048407 9.37 COL2A1 COL1A1
6 fibroblast growth factor binding GO:0017134 9.13 FGFR3 FGFR2 FGFR1
7 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
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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