Fetal Skeletal Disorders

Abstract

Skeletal disorders of the fetus are quite common. The incidence is about 5:1000 pregnancies. The disorders affect the extremities or parts of them (dysmelia), the whole skeleton (skeletal dysplasia), the skull (craniosynostosis) and the spine (dysostosis, caudal regression). About half of these diseases are complex. In the majority of cases the complex disorders are caused by single gene mutations or numeric or structural chromosomal aberrations. We explain the classification and diagnostic criteria for prenatal expert and screening ultrasound based on frequent disorders. The main diagnostic challenge concerning malformations of the limbs and craniosynostosis is to find out if they are isolated or symptoms of certain syndromes. In skeletal dysplasia it is clinically important to differentiate lethal entities from non-lethal.

Zusammenfassung

Skelettale Erkrankungen des Fetus sind mit 5:1000 Schwangerschaften relativ häufig. Betroffen sein können einzelne Abschnitte der Extremitäten (Dysmelien), das ganze Skelett (Skelettdysplasien), der knöcherne Schädel (Kraniosynostosen) und die Wirbelsäule (Dysostosen, kaudale Regression). In 50 % bestehen komplexe Krankheitsbilder. Für die Mehrzahl der Krankheiten sind genetische Ursachen (Einzelgen-Mutationen, numerische und strukturelle chromosomale Aberrationen) bekannt. Anhand häufiger Krankheitsbilder werden diagnostische Kriterien für die differenzierte Sonografie und das Ultraschall-Screening erläutert.

• Literatur

• 1 EUROCAT. Prevalence Tables. 2017 Im Internet: http://www.eurocat-network.eu ; Stand 11.2017
• 2 Bonafé L, Cormier-Daire V, Hall C. et al. Nosology and classification of genetic skeletal disorders: 2015 revision. Am J Med Genet A 2015; 167A: 2869-2892
• 3 Merz E, Eichhorn KH, von Kaisenberg C. et al. Arbeitsgruppe der DEGUM-Stufe III. Aktualisierte Qualitätsanforderungen an die weiterführende differenzierte Ultraschalluntersuchung in der pränatalen Diagnostik (= DEGUM-Stufe II) im Zeitraum von 18 + 0 bis 21 + 6 Schwangerschaftswochen. Ultraschall in Med 2012; 33: 593-596
• 4 von Kaisenberg C, Chaoui R, Häusler M. et al. Quality Requirements for the early Fetal Ultrasound Assessment at 11–13+6 Weeks of Gestation (DEGUM Levels II and III). Ultraschall in Med 2016; 37: 297-302
• 5 Syngelaki A, Chelemen T, Dagklis T. et al. Challenges in the diagnosis of fetal non-chromosomal abnormalities at 11–13 weeks. Prenat Diagn 2011; 31: 90-102
• 6 Oberg KC, Feenstra JM, Manske PR. et al. Developmental biology and classification of congenital anomalies of the hand and upper extremity. J Hand Surg Am 2010; 35: 2066-2076
• 7 Online Mendelian Inheritance in Man® OMIM. Im Internet: http://www.omim.org ; Stand 25.11.2017
• 8 London Medical Databases. Im Internet: http://face2gene.com ; Stand 25.11.2017
• 9 Stoll C, Alembik Y, Dott B. et al. Associated malformations in patients with limb reduction deficiencies. Eur J Med Genet 2010; 53: 286-290
• 10 Vasluian E, van der Sluis CK, van Essen AJ. et al. Birth prevalence for congenital limb defects in the northern Netherlands: a 30-year population-based study. BMC Musculoskelet Disord 2013; 14: 323
• 11 Gold NB, Westgate MN, Holmes LB. Anatomic and etiological classification of congenital limb deficiencies. Am J Med Genet Part A 2011; 155: 1225-1235
• 12 Bedard T, Lowry RB, Sibbald B. et al. Congenital limb deficiencies in Alberta – a review of 33 years (1980–2012) from the Alberta Congenital Anomalies Surveillance System (ACASS). Am J Med Genet A 2015; 167A: 2599-2609
• 13 Malik S. Syndactyly: phenotypes, genetics and current classification. Eur J Hum Genet 2012; 20: 817-824
• 14 Garrido-Allepuz C, Haro E, González-Lamuño D. et al. A clinical and experimental overview of sirenomelia: insight into the mechanisms of congenital limb malformations. Dis Model Mech 2011; 4: 289-299
• 15 Sharon-Weiner M, Sukenik-Halevy R, Tepper R. et al. Diagnostic accuracy, work-up, and outcomes of pregnancies with clubfoot detected by prenatal sonography. Prenat Diagn 2017; 37: 754-763
• 16 Hellmund A, Berg C, Geipel A. et al. Prenatal diagnosis of fetal akinesia deformation sequence (FADS): a study of 79 consecutive cases. Arch Gynecol Obstet 2016; 294: 697-707
• 17 Schramm T, Gloning KP, Minderer S. et al. Prenatal sonographic diagnosis of skeletal dysplasias. Ultrasound Obstet Gynecol 2009; 34: 160-170
• 18 Krakow D, Lachman RS, Rimoin DL. Guidelines for the prenatal diagnosis of fetal skeletal dysplasias. Genet Med 2009; 11: 127-133
• 19 Milks KS, Hill LM, Hosseinzadeh K. Evaluating skeletal dysplasias on prenatal ultrasound: an emphasis on predicting lethality. Pediatr Radiol 2017; 47: 134-145
• 20 Wang DC, Shannon P, Toi A. et al. Temporal lobe dysplasia: a characteristic sonographic finding in thanatophoric dysplasia. Ultrasound Obstet Gynecol 2014; 44: 588-594
• 21 Chitty LS, Khalil A, Barrett AN. et al. Safe, accurate, prenatal diagnosis of thanatophoric dysplasia using ultrasound and free fetal DNA. Prenat Diagn 2013; 33: 416-423
• 22 Schramm T. Prenatal sonografic diagnosis of craniosynostosis. In: Muenke M, Kress W, Collmann H. et al. (eds) Craniosynostoses: molecular genetics, principles of diagnosis, and treatment. 9. Monogr Hum Genet; 2011: 184-198
• 23 Lattanzi W, Barba M, Di Pietro L. et al. Genetic advances in craniosynostosis. Am J Med Genet A 2017; 173: 1406-1429
• 24 Mottet N, Martinovic J, Baeza C. et al. Think of the Conus Medullaris at the Time of Diagnosis of Fetal Sacral Agenesis. Fetal Diagn Ther 2017; 42: 137-143
• 25 Scherer S, Martucciello G, Lerone M. et al. HLXB9 (MNX1), sacral agenesis, and the Currarino syndrome. In: Erickson RP, Wynshaw-Boris AJ. (eds) Epstein's inborn errors of development: the molecular basis of clinical disorders of morphogenesis. 3.. ed New York: Oxford University Press; 2016: 715-720