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Major Craniofacial Defects: Case Series and Prenatal Diagnosis at the Instituto Nacional De Perinatología, Mexico

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Major Craniofacial Defects: Case Series and Prenatal Diagnosis at the Instituto Nacional De Perinatología, Mexico ARTÍCULO ORIGINAL Major craniofacial defects: case series and prenatal diagnosis at the Instituto Nacional de Perinatología, Mexico Berenice Velázquez-Torres,* Juan Manuel Gallardo-Gaona,* Sandra Acevedo-Gallegos,* José Antonio Ramírez-Calvo,* Jesús Andrés Benavides-Serralde,* Lisbeth Camargo-Marín,* Luz Engracia Cervantes-Parra,** Alejandro Martínez-Juárez,*** Mario Estanislao Guzmán-Huerta* * Unidad de Investigación del Departamento de Medicina Fetal. ** Medicina materno fetal, *** Departamento de Genética, Instituto Nacional de Perinatología. ABSTRACT Defectos craneofaciales mayores: serie de casos y diagnóstico prenatal en el Objective. To describe the prenatal diagnosis, characteris- Instituto Nacional de Perinatología tics, development, perinatal outcome, and final diagnosis of pregnancies complicated by fetuses with major craniofacial de- RESUMEN fects, at the Instituto Nacional de Perinatología, México, 1997- 2008. Material and methods. A retrospective, descriptive Objetivo. Describir el diagnóstico prenatal, características, study from January of 1997 to January 2008, analyzed 152 evolución, resultado perinatal y diagnóstico final de emba- pregnancies complicated by fetuses with major craniofacial de- razos complicados con fetos con defectos craneofaciales ma- fects, diagnosed at the Department of Fetal Medicine of the yores, atendidos en el Instituto Nacional de Perinatología en National Institute of Perinatology. Data were obtained from el periodo 1997-2008. Material y métodos. Estudio retros- patients clinical records. Results. The mean age was 28 ± 8 pectivo descriptivo, de enero de 1997 a enero 2008, en el cual years, with the largest number of cases between 20 and 24. se analizaron 152 embarazos complicados con fetos con de- The mean gestational age at diagnosis was 27.5 ± 6.4 gesta- fectos craneofaciales mayores que llevaron su seguimiento en tional weeks. The average termination of pregnancy was at 35 el Departamento de Medicina Materno-Fetal del Instituto ± 5 gestational weeks. In 43.4% of cases there were no major Nacional de Perinatología. Los datos se obtuvieron de los ex- structural defects associated with the facial defect. The most pedientes clínicos de las pacientes. Resultados. El prome- commonly associated structural alterations were cerebral, car- dio de edad fue de 28 ± 8 años, con el mayor número de diac, and limb abnormalities. Karyotyping was performed in casos entre los 20 y 24 años. La edad promedio al diagnósti- only 57 cases, and was abnormal in 25. Conclusions. Struc- co de hendiduras faciales fue de 27.5 semanas ± 6.4. La inte- tural ultrasound should be performed on all pregnant women rrupción del embarazo fue en promedio a la semana 35 ± 5. between weeks 18 and 24 for detection of major craniofacial En 43.4% de los casos no se encontraron otros defectos defects. Where defects are found, a thorough review of other estructurales mayores asociados al defecto facial. Las altera- structures should be carried out to determine whether the de- ciones estructurales con mayor frecuencia asociadas fueron fects are syndromic. A systematic and multidisciplinary las cerebrales y cardiacas y alteraciones de las extremidades. approach is essential to providing the best care and appropria- Sólo en 57 casos se realizó cariotipo y de éstos en 25 fue te advice to parents. anormal. Conclusiones. El ultrasonido estructural debe realizarse a todas las embarazadas entre las semanas 18 a 24 para la detección de defectos craneofaciales mayores; en los casos que lo presenten se deberá realizar la revisión minu- ciosa del resto de las estructuras, ante la posibilidad de que se trate de un caso sindromático. El abordaje sistemático y multidisciplinario es fundamental para brindar la mejor atención y proporcionar la adecuada asesoría a la pareja. Key words. Fetal. Craniofacial. Lip. Palate. Defects. Palabras clave. Fetal. Craneofacial. Labio. Paladar. Defectos. Revistai de Investigaciónes Clínica / Vol. 64, Núm. 5 / Septiembre-Octubre, 2012 / pp 420-428 INTRODUCTION and a flaw in fusion during any of the processes in- volved can lead to facial clefts. The exact mecha- In Mexico, facial defects are in many cases disco- nism of development of facial clefts is unknown, but vered only at birth, which heightens the emotional they are believed to have a multifactorial etiology in- impact on parents who expect a healthy newborn. In volving a combination of environmental and genetic this country, where prenatal diagnosis is still not causes in a critical period of embryonic development. available to the entire population, there is an inci- A number of genes involved in the development of dence of 1.39 defects for every 1,000 live births.1 cleft lip and palate have been identified, including Facial defects are the most frequent birth defects, TBX22, IRF6, and PVRL1,5,9,10 as have teratogens and among these the most common are cleft lip and including radiation, infections including toxoplas- palate.1,2 These have a significant impact on morbi- mosis, and deficiencies in folic acid and vitamin A.10 dity and mortality, quality of life, and the family Although from the embryological perspective fa- economy, as there is still a lack of specialized, multi- cial clefts are of distinct types, it is useful to study disciplinary perinatal attention in Mexico. them in a global manner, owing to their anatomical The craniofacial region is very complex, conside- location and their low frequency. In 1981, the Ame- ring all types of specialized tissues and structures rican Cleft Palate-Craniofacial Association grouped including, neural, sensory, respiratory, masticatory them into 5 categories in order to facilitate a gene- system, and in general the vascular, skeletal, ral overview and understand the etiology, evalua- muscular, endocrine and integumentary systems, tion, and treatment of the majority of craniofacial and therefore it is possible to find a wide range of de- defects. Facial clefts form part of type I, and include velopmental abnormalities, these may be classified encephaloceles and dysostosis.7-9 In 1976, Tessier as malformations, disruptions and deformations.3 proposed an anatomical classification, assigning a Craniofacial malformations constitute a compa- number to each malformation according to its posi- ratively rare combination of conditions occurring tion in relation to the median plane.4,5,12 Van der with varying degrees of severity in a multitude of Meulen, et al. devised a classification of facial patterns.3, 27-29 clefts, using the term “focal dysplasia”, based on A craniofacial cleft is a partial or total defect of embryological events in the formation of the face.7 any part of the cranial area or of the face. It can oc- In 1995, Nyberg, et al., also classified them into 5 cur in unilateral or bilateral form, and frequently types, taking the lip and palate as a reference. Other causes serious alterations in physical appearance classifications of facial clefts are based on the surgi- and structural function. The degree of severity runs cal approach to repair of facial defects.13 from a small hollow in the skin, hair loss, or al- Cleft lip can be unilateral or bilateral, and also be mond-shaped eyes, to clefts of the nose, lip, and pa- accompanied by unilateral or bilateral cleft palate, late, to absence of the nose or face.4 The type and and cleft palate can occur with the lip intact. Facial severity of the clefts are also related to the stage of clefts are also classified as syndromic, when associated development when the disruption occurred.5, 29 with other facial defects, and non-syndromic, when In 1984, Benacerraf, et al. recommended routine they occur in isolation. More than 350 syndromes facial examination as part of the prenatal structural associated with facial clefts have been described, ultrasound, particularly in patients with risk fac- among which the most frequently reported are tors such as family history of facial clefts, or expo- disruptive processes like amniotic band syndrome, sure to teratogens or infections.5,6 malformations like holoprosencephaly, and chromo- The majority of congenital facial defects are esta- somal and monogenic alterations, like trisomies 13, blished during the first 12 weeks of gestation.2,6-8 18, and 21 and Van der Woude syndrome, among The face is formed from the paraxial mesoderm, others. Other anomalies most frequently associated deriving from the frontonasal, maxillary, and man- with major craniofacial clefts are alterations in the dibular prominences. These form the primary palate, extremities, cardiac anomalies, and central nervous which will develop into the lip and anterior pala- system anomalies. 2,17-19,22 te. The palatal plates form the secondary palate, Structural ultrasound in the second trimester has which will form the hard and soft palates, and the- significantly increased the prenatal diagnosis of ma- se are fused with the primary palate in the ninth jor craniofacial defects and associated defects, with week.2,9,11 The complex embryology of the face allows highly variable detection rates that range from 5% for a wide variety of potential disruptions to these for isolated cleft palate to 91% for cleft lip and pala- vulnerable tissues during embryonic development, te with associated anomalies. Although ultrasound Velázquez-Torres B, et al. Major craniofacial defects. Rev Invest Clinn 2012; 64 (5): 420-428 421 has the disadvantage of low sensitivity, it has a very second trimester, and 54% (82/152) in the third tri- high specificity.7,16,20 mester. Karyotyping
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