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Thanatophoric dysplasia

MedGen UID:
21124
•Concept ID:
C0039743
•
Disease or Syndrome
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

Prenatal ultrasound findings and prenatal diagnosis of fetal skeletal dysplasia.
Li L, Jin X, Liu S, Fan H
J Clin Ultrasound 2024 Jun;52(5):575-587. Epub 2024 Apr 1 doi: 10.1002/jcu.23673. PMID: 38561934
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
Thanatophoric dysplasia in monozygotic twins discordant for cloverleaf skull: prenatal diagnosis, clinical and pathological findings.
Machin GA
Am J Med Genet 1992 Dec 1;44(6):842-3. doi: 10.1002/ajmg.1320440628. PMID: 1481860

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
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
Pattern recognition in bone dysplasias.
Spranger J
Prog Clin Biol Res 1985;200:315-42. PMID: 4080742

Diagnosis

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
Fetal Trigonocephaly (Strawberry Skull) in Early Pregnancy.
Gover A, Khatib N, Beloosesky R, Bronshtein M
J Ultrasound Med 2022 Feb;41(2):505-509. Epub 2021 Mar 26 doi: 10.1002/jum.15707. PMID: 33769585
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.
Kulkarni ML, Sureshkumar C, Venkataramana V, Koshy S, Bhagyavathi M, Reddy GS
Indian Pediatr 1994 Nov;31(11):1405-10. PMID: 7896342

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
HDAC6 deficiency or inhibition blocks FGFR3 accumulation and improves bone growth in a model of achondroplasia.
Ota S, Zhou ZQ, Romero MP, Yang G, Hurlin PJ
Hum Mol Genet 2016 Oct 1;25(19):4227-4243. Epub 2016 Aug 9 doi: 10.1093/hmg/ddw255. PMID: 27506979
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
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
Diagnostic imaging update in skeletal dysplasias.
Dominguez R, Talmachoff P
Clin Imaging 1993 Jul-Sep;17(3):222-34. doi: 10.1016/0899-7071(93)90115-4. PMID: 8364797

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
Thanatophoric Skeletal Dysplasia: A Case Report.
Anjum F, Daha SK, Shah G
JNMA J Nepal Med Assoc 2020 Mar;58(223):185-187. doi: 10.31729/jnma.4488. PMID: 32347827Free 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
Thanatophoric dysplasia.
Machado LE, Bonilla-Musoles F, Osborne NG
Ultrasound Obstet Gynecol 2001 Jul;18(1):85-6. doi: 10.1046/j.1469-0705.2001.00402.x. PMID: 11489235
Schneckenbecken dysplasia, radiology, and histology.
Nikkels PG, Stigter RH, Knol IE, van der Harten HJ
Pediatr Radiol 2001 Jan;31(1):27-30. doi: 10.1007/s002470000357. PMID: 11200994

Clinical prediction guides

Fetal Trigonocephaly (Strawberry Skull) in Early Pregnancy.
Gover A, Khatib N, Beloosesky R, Bronshtein M
J Ultrasound Med 2022 Feb;41(2):505-509. Epub 2021 Mar 26 doi: 10.1002/jum.15707. PMID: 33769585
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
The paradox of FGFR3 signaling in skeletal dysplasia: why chondrocytes growth arrest while other cells over proliferate.
Krejci P
Mutat Res Rev Mutat Res 2014 Jan-Mar;759:40-8. Epub 2013 Dec 1 doi: 10.1016/j.mrrev.2013.11.001. PMID: 24295726
Schneckenbecken dysplasia, radiology, and histology.
Nikkels PG, Stigter RH, Knol IE, van der Harten HJ
Pediatr Radiol 2001 Jan;31(1):27-30. doi: 10.1007/s002470000357. PMID: 11200994

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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