Details of Disease

General Information of Disease (ID: DISYWN2O)

• Disease Name: Achondroplasia
• Synonyms: Achondroplastic dwarfism; Achondroplastic physique; chondrodystrophia; Achondroplasia; ACH
• Disease Class: LD24: Skeletal anomaly
• Definition: Achondroplasia is the most common form of chondrodysplasia, characterized by rhizomelia, exaggerated lumbar lordosis, brachydactyly, and macrocephaly with frontal bossing and midface hypoplasia.
• Disease Hierarchy:
  DIS9SPWW: Osteochondrodysplasia
  DIS18AKT: FGFR3-related chondrodysplasia
  DISYWN2O: Achondroplasia
• ICD Code:
  ICD-11: ICD-11: LD24.00
  ICD-10: ICD-10: Q77.4
  ICD-9: ICD-9: 756.4
  Expand ICD-11: 'LD24.00
  Expand ICD-10: 'Q77.4
  Expand ICD-9: 756.4
• Disease Identifiers:
  MONDO ID: MONDO_0007037
  MESH ID: D000130
  UMLS CUI: C0001080
  OMIM ID: 100800
  MedGen ID: 1289
  Orphanet ID: 15
  SNOMED CT ID: 86268005

Drug-Interaction Atlas (DIA) of This Disease

This Disease is Treated as An Indication in 1 Approved Drug(s)

Drug Name	Drug ID	Highest Status	Drug Type	REF
Vosoritide	DMM9XL2	Approved	NA	[1]

This Disease is Treated as An Indication in 3 Clinical Trial Drug(s)

Drug Name	Drug ID	Highest Status	Drug Type	REF
TransCon CNP	DM6RVO4	Phase 2/3	NA	[2]
Recifercept	DML8N3Y	Phase 2	Antibody	[3]
SAR442501	DMGA3KZ	Phase 1	Antibody	[4]

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 6 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
CNP	TT71P0H	Strong	Biomarker	[5]
FGF1	TTMY81X	Strong	Genetic Variation	[6]
GH1	TTT3YKH	Strong	Biomarker	[7]
NPPC	TTRK0B9	Strong	Biomarker	[8]
NPR2	TTNB7IF	Strong	Genetic Variation	[9]
FGFR3	TTST7KB	Definitive	Autosomal dominant	[10]

This Disease Is Related to 1 DTP Molecule(s)

Gene Name	DTP ID	Evidence Level	Mode of Inheritance	REF
SLC20A1	DTMULXV	moderate	Genetic Variation	[11]

This Disease Is Related to 12 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
LEMD3	OTILAM4I	Limited	Genetic Variation	[12]
ARID1B	OTILK3Q7	moderate	Biomarker	[13]
COL10A1	OTC4G2YC	moderate	Genetic Variation	[14]
EDN3	OTN7Q9BE	moderate	Biomarker	[15]
EVC	OTRVYMXJ	moderate	Biomarker	[16]
IFT20	OTKJS2BZ	moderate	Biomarker	[17]
IL36RN	OT5CO95A	moderate	Genetic Variation	[18]
GRB10	OTCKXGRC	Strong	Genetic Variation	[19]
PTHLH	OTI1JF13	Strong	Altered Expression	[20]
SHOX	OTE0YZJO	Strong	Genetic Variation	[21]
SPRED2	OTUX685J	Strong	Biomarker	[22]
FGFR3	OTSAXDIL	Definitive	Autosomal dominant	[10]

References

• [1] FDA Approved Drug Products from FDA Official Website. 2021. Application Number: 214938.
• [2] ClinicalTrials.gov (NCT05598320) A Phase 2b, Multicenter, Double-Blind, Randomized, Placebo-controlled Trial Evaluating Efficacy and Safety of Subcutaneous Doses of TransCon CNP Administered Once Weekly for 52 Weeks in Children With Achondroplasia Followed by an Open Label Extension Period. U.S.National Institutes of Health.
• [3] ClinicalTrials.gov (NCT04638153) A Study Of Safety, Tolerability And Effectiveness Of Recifercept In Children With Achondroplasia. U.S. National Institutes of Health.
• [4] Clinical pipeline report, company report or official report of Sanofi
• [5] TransCon CNP, a Sustained-Release C-Type Natriuretic Peptide Prodrug, a Potentially Safe and Efficacious New Therapeutic Modality for the Treatment of Comorbidities Associated with Fibroblast Growth Factor Receptor 3-Related Skeletal Dysplasias.J Pharmacol Exp Ther. 2019 Sep;370(3):459-471. doi: 10.1124/jpet.119.258251. Epub 2019 Jun 24.
• [6] Effect of the achondroplasia mutation on FGFR3 dimerization and FGFR3 structural response to fgf1 and fgf2: A quantitative FRET study in osmotically derived plasma membrane vesicles.Biochim Biophys Acta. 2016 Jul;1858(7 Pt A):1436-42. doi: 10.1016/j.bbamem.2016.03.027. Epub 2016 Mar 31.
• [7] Physical, Mental, and Social Problems of Adolescent and Adult Patients with Achondroplasia.Calcif Tissue Int. 2019 Apr;104(4):364-372. doi: 10.1007/s00223-019-00518-z. Epub 2019 Feb 1.
• [8] Update on methods to enhance growth.Curr Opin Endocrinol Diabetes Obes. 2020 Feb;27(1):82-86. doi: 10.1097/MED.0000000000000513.
• [9] Expression of guanylyl cyclase-B (GC-B/NPR2) receptors in normal human fetal pituitaries and human pituitary adenomas implicates a role for C-type natriuretic peptide.Endocr Relat Cancer. 2012 Jul 22;19(4):497-508. doi: 10.1530/ERC-12-0129. Print 2012 Aug.
• [10] Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
• [11] Clinical characteristics, etiologies and pathophysiology of patients with severe short stature with severe GH deficiency: questionnaire study on the data registered with the foundation for growth science, Japan.Endocr J. 2006 Apr;53(2):259-65. doi: 10.1507/endocrj.53.259.
• [12] Mutations of the fibroblast growth factor receptor-3 gene in achondroplasia.Horm Res. 1996;45(1-2):108-10. doi: 10.1159/000184768.
• [13] Subcranial and orthognathic surgery for obstructive sleep apnea in achondroplasia.J Craniomaxillofac Surg. 2017 Dec;45(12):2028-2034. doi: 10.1016/j.jcms.2017.09.028. Epub 2017 Oct 5.
• [14] SSCP and segregation analysis of the human type X collagen gene (COL10A1) in heritable forms of chondrodysplasia.Am J Hum Genet. 1992 Oct;51(4):841-9.
• [15] Osmotic and non-osmotic regulation of arginine vasopressin (AVP) release, mRNA, and promoter activity in small cell lung carcinoma (SCLC) cells.Mol Cell Endocrinol. 1996 Oct 30;123(2):179-86. doi: 10.1016/s0303-7207(96)03912-3.
• [16] The gene for the Ellis-van Creveld syndrome is located on chromosome 4p16.Genomics. 1996 Jul 1;35(1):1-5. doi: 10.1006/geno.1996.0315.
• [17] Constitutively-active FGFR3 disrupts primary cilium length and IFT20 trafficking in various chondrocyte models of achondroplasia.Hum Mol Genet. 2018 Jan 1;27(1):1-13. doi: 10.1093/hmg/ddx374.
• [18] Acrodermatitis continua of Hallopeau is a clinical phenotype of DITRA: evidence that it is a variant of pustular psoriasis.Dermatology. 2013;226(1):28-31. doi: 10.1159/000346572. Epub 2013 Feb 15.
• [19] FGFR3 gene mutation plus GRB10 gene duplication in a patient with achondroplasia plus growth delay with prenatal onset.Orphanet J Rare Dis. 2016 Jul 2;11(1):89. doi: 10.1186/s13023-016-0465-4.
• [20] Intermittent PTH (1-34) injection rescues the retarded skeletal development and postnatal lethality of mice mimicking human achondroplasia and thanatophoric dysplasia.Hum Mol Genet. 2012 Sep 15;21(18):3941-55. doi: 10.1093/hmg/dds181. Epub 2012 May 24.
• [21] New roles of SHOX as regulator of target genes.Pediatr Endocrinol Rev. 2012 May;9 Suppl 2:733-8.
• [22] Gene disruption of Spred-2 causes dwarfism.J Biol Chem. 2005 Aug 5;280(31):28572-80. doi: 10.1074/jbc.M503640200. Epub 2005 Jun 9.