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THANATOPHORIC DYSPLASIA. Case Report and Review. Baltà Arandes R., Vila Cortés V., Jiménez Belio E., Simón Salvador C, Ruiz de Gopegui Valero R.M. Unit of Obstetrics and Prenatal Diagnosis of Hospital Universitario Son Espases of Palma de Mallorca, Balearic Islands, Spain. OBJECTIVE Review of one of the three most common skeletal dysplasias through the presentation of a case diagnosed in our Healthcare Unit and thus maintain and active behavior in the detection and management of these diseases. METHODS We present a case of Thanatophoric Dysplasia and a review of the three most common skeletal dysplasias. Finally, we examine the best diagnostic method and the most important lethal signs that are useful for management of the case and counseling the family. CONCLUSION The skeletal dysplasias are rare diseases of the genetic disorders identified during the neonatal period but physicians should be actualized in its diagnosis and management. The primary method of screening and study is the ultrasound. Additionally a definitive diagnosis is possible using cell-free fetal DNA in maternal plasma. It is important to know the most predictive signs and identify them in the ultrasound study. The most reliable sign is the calvarium demineralization. Identify the lethality of the disease can change the treatment and management of the case. INTRODUCTION The global prevalence of skeletal dysplasias worldwide has been seen of 2.4 cases of 10.000 births and the prevalence of lethal dysplasia 0.95-1.5 cases of 10.000 births. In general, they are rare diseases that become 5% of the genetic disorders identified during the neonatal period. The three most common skeletal dysplasias are: Thanatophoric Dysplasia, Osteogenesis imperfect type 2 and Achondrogenesis. Skeletal dysplasias can be identified in sonographic study early because the vast majority of the bones have an early ossification. THANATOPHORIC DYSPLASIA OSTEOGENESIS IMPERFECTA II ACHONDROGENESIS Type I Typ2 II Type II A/C Type IIB Type I (20%) Type II (80%) Prevalence 0,24-0,69 cases/10000 births 0,5 cases/10.000 births 0,09-0,23 cases/10.000 births Genetics HAD. Mut.R248C and Y373C in FGFR3 gene. HAD. Mut K650E in FGFR3 gene. The vast majority HAD with mutations in COL1A1 or COL1A2 genes. Exist others mutations less frequently and with other type of inheritance. HAR. Genes mutations.: IA: Mut.TRIP11 IB: Mut.DTDST. HAD. Mut. de novo COL2A1 gene. Most “de novo” Head circumference >95th Normal Macrocephaly Frontal bossing Cloverleaf skull Mineralization of cranium - + Mild Calvarial demineralization - Small chest Normal trunk length Thoracic circumference. + Mild (pectus excavatum) Thoracic circumference. Trunk length Ribs Short Beaded (pathognomonic) +/- Beading - Femur length (<20 weeks) <<3 rd Telephone receiver shape. Straight with flared metaphysis. <<<3rd 5th Normal Limb fractures - + + Occasional Polyhydramnios 50% Occasional - 25% Representative images BIBLIOGRAPHIC REFERENCES AND SOURCES OF IMAGES - Barkova E., Mohan U., Chitayat D., Keating S., Toi A., Frank J., Frank R.,Tomlinson G., Glanc P. Fetal skeletal dysplasias in a tertiary care center:radiology, pathology, and molecular analysis of 112 cases. Clin Genet 2014. - M. Bueno. Nomenclatura internacional y clasificación de las osteocondrodisplasias (1997). An Esp Pediatr 1999;50:229-236. - Glanc P. and Chitayat D. Prenatal diagnosis of the lethal skeletal dysplasias. UpToDate. Literature review current through: Aug 2014. - T.Schramm, K.P.Gloning, S.Minderer, C.Daumer-Haas, K.Hörtnagel, A.Nerlich and B.Tutschek. Prenatal sonographic diagnosis of skeletal dysplasias. Ultrasound Obstet Gynecol 2009;34:160-170. - Lyn S. Chitty, Asma Khalil, Angela N. Barrett, Eva Pajkrt, David R. Griffin and Tim J. Cole. Safe, accurate, prenatal diagnosis of thanatophoric dysplasiausing ultrasound and free fetal DNA. Prenatal Diagnosis 2013,33,416-423. (image B) - Edgar Abarca López E.A., Torres A.R., Donovan Casas Patiño D.C., Esteban Espíndola Benítez E.B. Thanatophoric dysplasia: case-based bioethical analysis. Medwave 2014;14(3)e5943 doi: 10.5867 - http://www.fetalultrasound.com - http://www.iame.com OUR CASE Pregnancy of 20 weeks diagnosed of skeletal dysplasia through ultrasound study and proceeded a legal abortion at 22 weeks. Anatomy confirmed the diagnosis. THE MOST PREDICTIVE SIGNS OF SKELETAL DYSPLASIA Femur length >5mm below -2SD for gestational age. Femur:foot length <1 Femur length:abdominal circumference <0.16 MANAGEMENT Continue pregnancy controls. Legal abortion may be an option in Spain. Obtain information and counseling from organizations and affected family associations. DIAGNOSIS Ultrasound is the primary method of screening and study. A definitive diagnosis can be established through the study of cffDNA* in maternal plasma. It offers an accurate and early definitive, but safe, approach to diagnosis and to exclude recurrence. *cffDNA: cell-free fetal DNA LETHALITY Presence of pulmonary hypoplasia and decreased chest circumference. Calvarial demineralization Mild transducer pressure over the cranial vault results in flattening of the skull www.iame.com www.fetalultrasound.com www.fetalultrasound.com www.medwave.cl UpToDate® UpToDate® UpToDate®
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