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La aparición de defectos congénitos produce una gran ansiedad en la familia y una enorme demanda asistencial. El objetivo principal radica en la redacción de las recomendaciones de buenas prácticas que sirvan de guía a los profesionales sanitarios para el diagnóstico clínico-genético de defectos congénitos.

Purpose:Radial ray deficiencies are characterized by unilateral or bilateral absence of varying portions of the radius and thumb. Both isolated and syndromic forms have been described, and although for some of the syndromes the causal gene has been identified, many patients remain without a genetic diagnosis.Methods:In this study, a cohort of 54 patients with radial ray deficiencies was screened for genomic aberrations by molecular karyotyping.Results:In 8 of 54 cases, an aberration was detected. Two unrelated patients inherited a 1q21.1 microduplication from a healthy parent, whereas in a third patient, a 16p13.11 microduplication was identified. Two other interesting microdeletions were detected: a 10q24.3 deletion at the split hand–foot malformation (SHFM3) locus and a 7p22.1 deletion including the RAC1 gene.Conclusion:The finding of these microduplications may just be coincidental or, alternatively, they may illustrate the broad phenotypic spectrum of these microduplications. Duplications in the 10q24.3 region result in split hand–foot malformations, and our observation indicates that deletions may cause radial ray defects. Finally, a candidate gene for radial ray deficiencies was detected in the 7p22.1 deletion. RAC1 plays an important role in the canonical Wnt pathway and conditional RAC1 knockout mice exhibit truncated-limb defects.Genet Med 2013:15(3):195–202

Mycophenolate mofetil (MMF) is a widely prescribed immunosuppressive agent after solid organ transplantation. Potential teratogenic effects after in utero exposure to MMF in experimental studies and clinical observations in humans has been postulated in recent literature. However, a specific pattern of malformation has not been identified yet. We present a newborn patient, born to a recipient of renal transplantation, who became pregnant while taking MMF as immunosuppressive therapy. The newborn exhibited cleft lip and palate, bilateral microtia and atretic external auditory canals, chorioretinal coloboma, hypertelorism, and micrognathia. An extensive review of the literature documented six other cases with similar malformations after in utero exposure to MMF. A consistent pattern of malformations comprising cleft lip and palate, microtia and external auditory canals could be observed in five of the six cases. A different malformative pattern observed in one of the patients could be attributed to a different agent rather than MMF. The possible teratogenic effects of other immunosuppressive drugs, such as tacrolimus and prednisone, to which this patient was also exposed, are discussed herein. In addition, the differential diagnosis with other dysmorphic syndromes that can present with a similar phenotype, such as CHARGE syndrome, 18q deletion and hypertelorism‐microtia‐clefting (HMC) syndrome, is presented. We conclude that in utero exposure to MMF can cause a characteristic phenotype and propose the existence of a mycophenolate‐associated embryopathy whose main features are: cleft lip and palate, microtia with atresia of external auditory canal, micrognathia and hypertelorism. Ocular anomalies, corpus callosum agenesis, heart defects, kidney malformations, and diaphragmatic hernia may be part of the phenotypic spectrum of MMF embryopathy. The human teratogenicity of MMF is reinforced by this report, and the current contraceptive recommendations about its use in fertile women are stressed. © 2007 Wiley‐Liss, Inc.

We describe a 1,000-g twin fetus with absent kidneys and ureters, anal atresia and minimal evidence of external genitalia, and hypoplastic lower limbs with absent feet. A postmortem arteriogram showed a large single umbilical artery in direct continuation with the abdominal aorta, a unique anomaly almost always related to sirenomelia. We discuss the possible diagnosis of this case as sirenomelia or caudal dysgenesis, and the controversy as to whether they are two related or separate entities. Am. J. Med. Genet. 69:409–412, 1997. © 1997 Wiley-Liss, Inc.