Skeletal dysplasias of the fetus and infant: comprehensive review and our experience over a 10-year period
Authors:
Marta Ježová 1; Denisa Pavlovská 2; Ilga Grochová 3; Andrea Michenková 3; Pavel Vlašín 3
Authors‘ workplace:
Ústav patologie, Fakultní nemocnice Brno a Lékařská fakulta Masarykovy Univerzity, Brno
1; Klinika dětské radiologie, Fakultní nemocnice Brno
2; Centrum prenatální diagnostiky s. r. o, Brno
3
Published in:
Čes.-slov. Patol., 59, 2023, No. 2, p. 68-79
Category:
Original Articles
Overview
We present a comprehensive review dealing with rare genetic skeletal disorders. More than 400 entities are included in the latest classification. The most severe or lethal phenotypes are identifiable in the prenatal period and the pregnancy can be terminated. Perinatal autopsy and posmortem X-rays are crucial in providing a definitive diagnosis. The number of cases confirmed by genetic testing is increasing. We report our own experience with genetic skeletal disorders based on 41 illustrative fetal and neonatal cases which we encountered over a 10-year period. Thanatophoric dysplasia and osteogenesis imperfecta represent approximately half of the cases coming to autopsy. Achondrogenesis type 2 and hypochondrogenesis, short-rib dysplasia, chondrodysplasia punctata, campomelic dysplasia and achondroplasia are less common. Skeletal dysplasias with autosomal recessive inheritance are the least frequent, e.g. perinatally lethal hypophophatasia, achondrogenesis type 1A, diastrophic dysplasia/atelosteogenesis type 2 or mucolipidosis type 2 (I cell disease).
Keywords:
osteogenesis imperfecta – prenatal diagnosis – fetus – skeletal dysplasia – thanatophoric dysplasia – achondrogenesis
Sources
1. Bonafe L, Cormier-Daire V, Hall C et al. Nosology and classification of genetic skeletal disorders: 2015 revision. Am J Med Genet Part A 2015; 167A: 2869–2892.
2. Konstantinidou AE, Agrogiannis G, Sifakis S et al. Genetic skeletal disorders of the fetus and infant: pathologic and molecular findings in a series of 41 cases. Birth Defects Res A Clin Mol Teratol 2009; 85(10): 811–821.
3. Spranger JW, Brill PW, Nishimura G, Superti- Furga A, Unger S. Bone dysplasias. An atlas of genetic disorders of skeletal developement. New York: Oxford University Press; 2012.
4. Nikkels PGJ. The skeletal system. In: Keeling JW, Khong TY, eds. Fetal and neonatal pathology (4th ed). London: Springer-Verlag; 2007: 770–794.
5. Mařík I, Maříková A, Povýšil C. Kostní genetické choroby. In: Povýšil C, ed. Patomorfologie chorob kostí a kloubů. Praha: Galén; 2017, 17–101.
6. Sillence DO, Horton WA, Rimoin DL. Morphologic studies in the skeletal dysplasias. Am J Pathol 1979; 96(3): 813–870.
7. Wiggelsworth JS, Desai R, Guerrini P. Fetal lung hypoplasia: biochemical and structural variations and their possible significance. Arch Dis Child 1981; 56: 606–615.
8. De Paepe ME, Friedman RM, Gundogan F, Pinar H. Postmortem lung weight/body weight standards for term and preterm infants. Pediatr Pulm 2005; 40: 445–448.
9. Wilkinson D, de Crespigny L, Xafis V. Ethical language and decision-making for prenatally diagnosed lethal malformations. Semin Fetal Neonatal Med 2014; 19(5): 306–311.
10. Pauli RM. Achondroplasia: a comprehensive clinical review. Orphanet J Rare Dis 2019; 14(1): 1.
11. Nikkel SM, Major N, King JW. Growth and development in thanatophoric dysplasia - an update 25 years later. Clin Case Rep 2013; 1(2): 75–77.
12. Pokrývková M, Poláčková R. Thanatoforická dysplázie. Pediatr Praxi 2013; 14(6), 386-388.
13. Vogt C, Blaas HG. Thanatophoric dysplasia: autopsy findings over a 25-year period. Pediatr Dev Pathol 2013; 16(3): 160–167.
14. Gregersen PA, Savarirayan R. Type II Collagen Disorders Overview. In: Adam MP, Ardinger HH, Pagon RA et al, eds. GeneReviews ® [Internet]. Seattle (WA): University of Washington; 2008 [updated 2019 Apr 25].
15. Krakow D. Skeletal dysplasias. Clin Perinatol 2015; 42(2): 301–319.
16. Saldino RM. Lethal short-limbed dwarfism: achondrogenesis and thanatophoric dwarfism. Am J Roentgenol Radium Ther Nucl Med 1971; 112(1): 185–197.
17. Quereshi F, Johnson SF, Johnson MP, Hume RF, Evans MI, Yang SS. Histopathology of Fetal Diastrophic Dysplasia. Am J Med Genet 1995; 56: 300-303.
18. Borochowitz Z, Lachman R, Adomian GE et al. Achondrogenesis type I: Delineation of further heterogeneity and identification of two distinct subgroups. J Pediatr 1988; 112: 23–31.
19. Huber C, Cormier-Daire V. Ciliary disorder of the skeleton. Am J Med Genet C Semin Med Genet 2012; 160C(3): 165–174.
20. Chen H. Asphyxiating Thoracic Dystrophy. In: Chen H, ed. Atlas of Genetic Diagnosis and Counseling. New York: Springer-Verlag; 2012: 157–166.
21. Keppler-Noreuil KM, Adam MP, Welch J, Muilenburg A, Willing MC. Clinical insights gained from eight new cases and review of reported cases with Jeune syndrome (asphyxiating thoracic dystrophy). Am J Med Genet Part A 2011; 155A(5): 1021–1032.
22. Victoria T, Zhu X, Lachman R et al. What Is New in Prenatal Skeletal Dysplasias? Am J Roentgenol 2018; 210: 1022–1033.
23. Lefebvre M, Dufernez F, Bruel AL et al. Severe X-linked chondrodysplasia punctata in nine new female fetuses. Prenat Diagn 2015; 35(7): 675–684.
24. Bendová K, Poláčková R, Gřegořová A, Šilhánová E. Kampomelická dysplázie. Pediatr praxi 2015; 16(4): 264–266.
25. Unger S, Scherer G, Superti-Furga A. Campomelic dysplasia In: Adam MP, Ardinger HH, Pagon RA et al, eds. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 2008 [updated 2021 Mar 18].
26. Pyott SM, Pepin MG, Schwarze U et al. Reccurence of perinatal lethal osteogenesis imperfecta in sibships: Parsing the risk between parental mosaicism for dominant mutations and autosomal recessive inheritance. Genet Med 2011; 13(2): 125-130.
27. Valadares ER, Carneiro TB, Santos PM, Oliveira AC, Zabel B. What is new in genetics and osteogenesis imperfecta classification? J Pediatr 2014; 90: 536–541.
28. Byers PH, Krakow D, Nunes ME, Pepin M. Genetic evaluation of suspected osteogenesis imperfecta. Genet Med 2006; 8(6): 383–388.
29. Shohat M, Rimoin DL, Gruber HE, Lachman RS. Perinatal lethal hypophosphatasia; clinical, radiologic and morphologic findings. Pediatr Radiol 1991; 21(6): 421–427.
30. Šumník Z, Souček O, Lebl J. Hypofosfatázie: Kdy na ni myslet a jak ji léčit. Pediatr praxi 2016; 17(3): 146–149.
31. Elleder M, Poupětová H, Zeman J et al. Mukolipidóza II (I cell disease). Popis prvého případu v České republice a prenatální diagnóza v rodině. Čas Lék čes 1997; 136(22): 702–703.
32. Unger S, Paul DA, Nino MC et al. Mucolipidosis II presenting as severe neonatal hyperparathyroidism. Eur J Pediatr 2005; 164(4): 236–243.
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Czecho-Slovak Pathology
2023 Issue 2
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