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Thanatophoric dysplasia

MedGen UID:
21124
•Concept ID:
C0039743
•
Congenital Abnormality
Synonym: Thanatophoric dwarfism
SNOMED CT: Thanatophoric dwarfism (29352008); TD - Thanatophoric dwarfism (29352008); Thanatophoric short stature (29352008); Thanatophoric dysplasia (29352008); Thanatophoric dwarfism syndrome (29352008); Thanatophoric dwarf (29352008)
Modes of inheritance:
Autosomal dominant inheritance
MedGen UID:
141047
•Concept ID:
C0443147
•
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in heterozygotes. In the context of medical genetics, an autosomal dominant disorder is caused when a single copy of the mutant allele is present. Males and females are affected equally, and can both transmit the disorder with a risk of 50% for each child of inheriting the mutant allele.
Not genetically inherited
MedGen UID:
988794
•Concept ID:
CN307044
•
Finding
Source: Orphanet
clinical entity without genetic inheritance.
See: This record
Autosomal dominant inheritance (Orphanet)
Not genetically inherited (Orphanet)
 
Related gene: FGFR3
 
Monarch Initiative: MONDO:0017042
Orphanet: ORPHA2655

Disease characteristics

Excerpted from the GeneReview: Thanatophoric Dysplasia
Thanatophoric dysplasia (TD) is a short-limb skeletal dysplasia that is usually lethal in the perinatal period. TD is divided into subtypes: TD type 1 is characterized by micromelia with bowed femurs and, uncommonly, the presence of craniosynostosis of varying severity. TD type 2 is characterized by micromelia with straight femurs and uniform presence of moderate-to-severe craniosynostosis with cloverleaf skull deformity. Other features common to type 1 and type 2 include: short ribs, narrow thorax, relative macrocephaly, distinctive facial features, brachydactyly, hypotonia, and redundant skin folds along the limbs. Most affected infants die of respiratory insufficiency shortly after birth. Rare long-term survivors have been reported. [from GeneReviews]
Full text of GeneReview (by section):
Summary  |  GeneReview Scope  |  Diagnosis  |  Clinical Characteristics  |  Genetically Related (Allelic) Disorders  |  Differential Diagnosis  |  Management  |  Genetic Counseling  |  Resources  |  Molecular Genetics  |  Chapter Notes  |  References
Authors:
Tegan French  |  Ravi Savarirayan   view full author information

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
Follow this link to review classifications for Thanatophoric dysplasia in Orphanet.

Professional guidelines

PubMed

Diagnosis of thanatophoric dysplasia using clinical exome screening.
Holub M, Sekowská M, Smetanová D, Koudová M, Sobolová K, Šinská A, Heřman H
Ceska Gynekol 2023;88(5):376-379. doi: 10.48095/cccg2023376. PMID: 37932055
Fetal autopsy for the diagnosis of skeletal dysplasia and comparison with prenatal ultrasound findings over a 16-year period.
Ozdemir O, Aksoy F, Sen C
J Perinat Med 2022 Nov 25;50(9):1239-1247. Epub 2022 Jul 1 doi: 10.1515/jpm-2022-0201. PMID: 35771677
Prenatal sonographic findings and prognosis of craniosynostosis diagnosed during the fetal and neonatal periods.
Harada A, Miyashita S, Nagai R, Makino S, Murotsuki J
Congenit Anom (Kyoto) 2019 Jul;59(4):132-141. Epub 2018 Sep 5 doi: 10.1111/cga.12308. PMID: 30132994

Recent clinical studies

Etiology

Diagnosis of thanatophoric dysplasia using clinical exome screening.
Holub M, Sekowská M, Smetanová D, Koudová M, Sobolová K, Šinská A, Heřman H
Ceska Gynekol 2023;88(5):376-379. doi: 10.48095/cccg2023376. PMID: 37932055
Should we offer prenatal exome sequencing for intrauterine growth restriction or short long bones? A systematic review and meta-analysis.
Mone F, Mellis R, Gabriel H, Baptiste C, Giordano J, Wapner R, Chitty LS
Am J Obstet Gynecol 2023 Apr;228(4):409-417.e4. Epub 2022 Oct 7 doi: 10.1016/j.ajog.2022.09.045. PMID: 36209938
Lethal and life-limiting skeletal dysplasias: Selected prenatal issues.
Stembalska A, Dudarewicz L, Śmigiel R
Adv Clin Exp Med 2021 Jun;30(6):641-647. doi: 10.17219/acem/134166. PMID: 34019743
National survey of prevalence and prognosis of thanatophoric dysplasia in Japan.
Sawai H, Oka K, Ushioda M, Nishimura G, Omori T, Numabe H, Kosugi S
Pediatr Int 2019 Aug;61(8):748-753. Epub 2019 Aug 27 doi: 10.1111/ped.13927. PMID: 31247124Free PMC Article
Bone dysplasia series. Achondroplasia, hypochondroplasia and thanatophoric dysplasia: review and update.
Lemyre E, Azouz EM, Teebi AS, Glanc P, Chen MF
Can Assoc Radiol J 1999 Jun;50(3):185-97. PMID: 10405653

Diagnosis

Skeletal dysplasias of the fetus and infant: comprehensive review and our experience over a 10-year period.
Ježová M, Pavlovská D, Grochová I, Michenková A, Vlašín P
Cesk Patol 2023 Summer;59(2):68-79. PMID: 37468326
Should we offer prenatal exome sequencing for intrauterine growth restriction or short long bones? A systematic review and meta-analysis.
Mone F, Mellis R, Gabriel H, Baptiste C, Giordano J, Wapner R, Chitty LS
Am J Obstet Gynecol 2023 Apr;228(4):409-417.e4. Epub 2022 Oct 7 doi: 10.1016/j.ajog.2022.09.045. PMID: 36209938
Lethal and life-limiting skeletal dysplasias: Selected prenatal issues.
Stembalska A, Dudarewicz L, Śmigiel R
Adv Clin Exp Med 2021 Jun;30(6):641-647. doi: 10.17219/acem/134166. PMID: 34019743
Non-invasive prenatal sequencing for multiple Mendelian monogenic disorders using circulating cell-free fetal DNA.
Zhang J, Li J, Saucier JB, Feng Y, Jiang Y, Sinson J, McCombs AK, Schmitt ES, Peacock S, Chen S, Dai H, Ge X, Wang G, Shaw CA, Mei H, Breman A, Xia F, Yang Y, Purgason A, Pourpak A, Chen Z, Wang X, Wang Y, Kulkarni S, Choy KW, Wapner RJ, Van den Veyver IB, Beaudet A, Parmar S, Wong LJ, Eng CM
Nat Med 2019 Mar;25(3):439-447. Epub 2019 Jan 28 doi: 10.1038/s41591-018-0334-x. PMID: 30692697
Thanatophoric dysplasia: A review.
Wainwright H
S Afr Med J 2016 May 25;106(6 Suppl 1):S50-3. doi: 10.7196/SAMJ.2016.v106i6.10993. PMID: 27245526

Therapy

Should we offer prenatal exome sequencing for intrauterine growth restriction or short long bones? A systematic review and meta-analysis.
Mone F, Mellis R, Gabriel H, Baptiste C, Giordano J, Wapner R, Chitty LS
Am J Obstet Gynecol 2023 Apr;228(4):409-417.e4. Epub 2022 Oct 7 doi: 10.1016/j.ajog.2022.09.045. PMID: 36209938
Safe, accurate, prenatal diagnosis of thanatophoric dysplasia using ultrasound and free fetal DNA.
Chitty LS, Khalil A, Barrett AN, Pajkrt E, Griffin DR, Cole TJ
Prenat Diagn 2013 May;33(5):416-23. Epub 2013 Feb 14 doi: 10.1002/pd.4066. PMID: 23408600Free PMC Article
A novel FGFR3-binding peptide inhibits FGFR3 signaling and reverses the lethal phenotype of mice mimicking human thanatophoric dysplasia.
Jin M, Yu Y, Qi H, Xie Y, Su N, Wang X, Tan Q, Luo F, Zhu Y, Wang Q, Du X, Xian CJ, Liu P, Huang H, Shen Y, Deng CX, Chen D, Chen L
Hum Mol Genet 2012 Dec 15;21(26):5443-55. Epub 2012 Sep 26 doi: 10.1093/hmg/dds390. PMID: 23014564Free PMC Article
Intermittent PTH (1-34) injection rescues the retarded skeletal development and postnatal lethality of mice mimicking human achondroplasia and thanatophoric dysplasia.
Xie Y, Su N, Jin M, Qi H, Yang J, Li C, Du X, Luo F, Chen B, Shen Y, Huang H, Xian CJ, Deng C, Chen L
Hum Mol Genet 2012 Sep 15;21(18):3941-55. Epub 2012 May 24 doi: 10.1093/hmg/dds181. PMID: 22634226
The population-based prevalence of achondroplasia and thanatophoric dysplasia in selected regions of the US.
Waller DK, Correa A, Vo TM, Wang Y, Hobbs C, Langlois PH, Pearson K, Romitti PA, Shaw GM, Hecht JT
Am J Med Genet A 2008 Sep 15;146A(18):2385-9. doi: 10.1002/ajmg.a.32485. PMID: 18698630Free PMC Article

Prognosis

Lethal and life-limiting skeletal dysplasias: Selected prenatal issues.
Stembalska A, Dudarewicz L, Śmigiel R
Adv Clin Exp Med 2021 Jun;30(6):641-647. doi: 10.17219/acem/134166. PMID: 34019743
Fetal magnetic resonance imaging of skeletal dysplasias.
Gilligan LA, Calvo-Garcia MA, Weaver KN, Kline-Fath BM
Pediatr Radiol 2020 Feb;50(2):224-233. Epub 2019 Nov 27 doi: 10.1007/s00247-019-04537-8. PMID: 31776601
National survey of prevalence and prognosis of thanatophoric dysplasia in Japan.
Sawai H, Oka K, Ushioda M, Nishimura G, Omori T, Numabe H, Kosugi S
Pediatr Int 2019 Aug;61(8):748-753. Epub 2019 Aug 27 doi: 10.1111/ped.13927. PMID: 31247124Free PMC Article
Non-invasive prenatal sequencing for multiple Mendelian monogenic disorders using circulating cell-free fetal DNA.
Zhang J, Li J, Saucier JB, Feng Y, Jiang Y, Sinson J, McCombs AK, Schmitt ES, Peacock S, Chen S, Dai H, Ge X, Wang G, Shaw CA, Mei H, Breman A, Xia F, Yang Y, Purgason A, Pourpak A, Chen Z, Wang X, Wang Y, Kulkarni S, Choy KW, Wapner RJ, Van den Veyver IB, Beaudet A, Parmar S, Wong LJ, Eng CM
Nat Med 2019 Mar;25(3):439-447. Epub 2019 Jan 28 doi: 10.1038/s41591-018-0334-x. PMID: 30692697
Prenatal sonographic findings and prognosis of craniosynostosis diagnosed during the fetal and neonatal periods.
Harada A, Miyashita S, Nagai R, Makino S, Murotsuki J
Congenit Anom (Kyoto) 2019 Jul;59(4):132-141. Epub 2018 Sep 5 doi: 10.1111/cga.12308. PMID: 30132994

Clinical prediction guides

Collagen X Marker Levels are Decreased in Individuals with Achondroplasia.
Carroll RS, Olney RC, Duker AL, Coghlan RF, Mackenzie WG, Ditro CP, Brown CJ, O'Connell DA, Horton WA, Johnstone B, Espiner EA, Prickett TCR, Bober MB
Calcif Tissue Int 2022 Jul;111(1):66-72. Epub 2022 Mar 11 doi: 10.1007/s00223-022-00966-0. PMID: 35275235
Lethal and life-limiting skeletal dysplasias: Selected prenatal issues.
Stembalska A, Dudarewicz L, Śmigiel R
Adv Clin Exp Med 2021 Jun;30(6):641-647. doi: 10.17219/acem/134166. PMID: 34019743
Non-invasive prenatal sequencing for multiple Mendelian monogenic disorders using circulating cell-free fetal DNA.
Zhang J, Li J, Saucier JB, Feng Y, Jiang Y, Sinson J, McCombs AK, Schmitt ES, Peacock S, Chen S, Dai H, Ge X, Wang G, Shaw CA, Mei H, Breman A, Xia F, Yang Y, Purgason A, Pourpak A, Chen Z, Wang X, Wang Y, Kulkarni S, Choy KW, Wapner RJ, Van den Veyver IB, Beaudet A, Parmar S, Wong LJ, Eng CM
Nat Med 2019 Mar;25(3):439-447. Epub 2019 Jan 28 doi: 10.1038/s41591-018-0334-x. PMID: 30692697
Paternal age effect mutations and selfish spermatogonial selection: causes and consequences for human disease.
Goriely A, Wilkie AO
Am J Hum Genet 2012 Feb 10;90(2):175-200. doi: 10.1016/j.ajhg.2011.12.017. PMID: 22325359Free PMC Article
The cerebral cortex malformation in thanatophoric dysplasia: neuropathology and pathogenesis.
Hevner RF
Acta Neuropathol 2005 Sep;110(3):208-21. doi: 10.1007/s00401-005-1059-8. PMID: 16133544

Recent systematic reviews

Should we offer prenatal exome sequencing for intrauterine growth restriction or short long bones? A systematic review and meta-analysis.
Mone F, Mellis R, Gabriel H, Baptiste C, Giordano J, Wapner R, Chitty LS
Am J Obstet Gynecol 2023 Apr;228(4):409-417.e4. Epub 2022 Oct 7 doi: 10.1016/j.ajog.2022.09.045. PMID: 36209938

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