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J Assist Reprod Genet. 2010 January; 27(1): 63–64.
Published online 2009 December 29. doi:  10.1007/s10815-009-9374-y
PMCID: PMC2826625

Reply to: comment on Trujillo-Tiebas MJ et al. J Assist Reprod Genet DOI 10.1007/s10815-009-9339-1

Dear Dr. Dong-Zhi Li,

Firstly, we thank you for the interest with which you have read our article as well as the remarks you have made in response [1]. As you mention, skeletal dysplasias are indeed a very diverse group of pathologies for which ultrasound prenatal diagnosis is a difficult prospect that poses a substantial challenge for professionals. For this reason, our Clinical Genetics Service is made up of a consultation section and both a cytogenetics and molecular laboratory. The aim of our paper was to give an account of our experience over a nine-year period in a GENETICS laboratory while summarizing the laboratory’s results in providing molecular diagnosis based on samples coming in from both our own institution as well as other accredited centers. Our intent was to stress the great advantages offered by a comprehensive service which, in addition to molecular diagnosis, provides both genetic counseling and cytogenetic and molecular studies.

In Spain, termination of pregnancy is currently permitted by law until the twenty-second week. One of the causes justifying lawful pregnancy termination is the detection of ultrasound-documented alterations which render the developing fetus inviable as well as those causing severe fetal illness. Our hospitals do not perform pregnancy-termination procedures, and the abortuses received by our service are sent to us by legal institutions specializing in such operations. All the samples that become part of our studies are the product of fetuses deemed by the law as suitable for such purposes.

The time elapsed between detection and gestation is a limiting factor. It can be assumed that, in the near future, prenatal diagnosis of the most common types of bone dysplasia will be performed by means of a screening process carried out in a timely and cost-effective manner, thus limiting the number of pregnancies terminated because of severe skeletal alterations.

Couples seeking genetic counseling in our center are informed of the risks associated with invasive techniques and the options open to them under Spanish law at the moment they receive information on the most likely diagnosis. Therefore, couples choose to pursue prenatal diagnosis of their pregnancy and then are free to decide whether to continue the pregnancy or not based on the findings of ultrasound testing and genetic studies. Orphanet suggests in genetic counseling for thanatophoric dysplasia that <<Recurrence risk is not significantly increased over that of the general population. Germline mosaicism in healthy parents, although not previously reported, remains a theoretical possibility. Prenatal diagnosis is clinically available, and is reliable both through sonography and through molecular studies>> [2]

Our experience has shown there to be two main types of situations:

  1. Previous pregnancy diagnosed with bone dysplasia: recurrence has been shown to be low prevalent in these pathologies [3] but the risk of repeated mutations may be greater than in the general population since it cannot be proven that no de novo mutation in the fetus has occurred [4]. Because it is the patients themselves who defend their right to know, they fund these studies themselves. (This information is not contained in the article.) therefore, these individuals take on the risk of losing the fetus, though our center has a low incidence of fetal loss (<1.5/% in chorionic villi).
  2. When the time of gestation has surpassed the period during which it is legal to terminate the pregnancy: The study is requested as a part of the pregnancy plan, the perinatal follow-up program, and by virtue of the right of parents to have this information.

Some couples who receive ultrasound prenatal diagnoses without molecular confirmation though having been given previous genetic counseling continue with the pregnancy. Many times, these pregnancies result in other diagnoses (referred to in the article as post-natal diagnosis, such as renal polycystosis, cardiopathy, etc.). Other couples, having gone through a follow-up process adapted to the pathological findings of ultrasound testing, opted to discontinue pregnancy in a lawful manner.

It is true that the article has a typographical error, since the STR markers used in the QF-PCR assay included chromosome 21 rather than chromosome 15. Nonetheless, this information appeared in accurate form in the bibliographical reference [5].

We agree with Dr. Li in that prenatal identification of skeletal dysplasias is quite challenging, and that it would be much more effective if there were interdisciplinary efforts made between all the specialties involved. Complementary radiological, anatomic pathology, and molecular studies must be made available for there to be conclusive diagnoses. We also believe that conducting a study on abortuses found via ultrasound to have skeletal alterations may assist in expanding the knowledge of these pathologies.


Thanks to Oliver Shaw for his collaboration in the English version of the manuscript and to Fundación Ramón Areces (Ref. 4715/001) for supporting this work.


1. Trujillo-Tiebas MJ, Fenollar-Cortés M, Lorda-Sánchez I, Díaz-Recasens J, Carrillo Redondo A, Ramos-Corrales C, et al. Prenatal diagnosis of skeletal dysplasia due to FGFR3 gene mutations: a 9-year experience : Prenatal diagnosis in FGFR3 gene. J Assist Reprod Genet. 2009;26(8):455–460. doi: 10.1007/s10815-009-9339-1. [PMC free article] [PubMed] [Cross Ref]
3. Natacci F, Baffico M, Cavallari U, Bedeschi MF, Mura I, Paffoni A, Setti PL, Baldi M, Lalatta F. Germline mosaicism in achondroplasia detected in sperm DNA of the father of three affected sibs. Am J Med Genet A. 2008;146A(6):784–786. doi: 10.1002/ajmg.a.32228. [PubMed] [Cross Ref]
4. Crow JF. The origins, patterns and implications of human spontaneous mutation. Nat Rev Genet. 2000;1:40–47. doi: 10.1038/35049558. [PubMed] [Cross Ref]
5. Adinolfi M, Pertl B, Sherlock J. Rapid detection of aneuploidies by microsatellite and the quantitative fluorescent polymerase chain reaction. Prenat Diagn. 1997;17:1299–1311. doi: 10.1002/(SICI)1097-0223(199712)17:13<1299::AID-PD297>3.0.CO;2-H. [PubMed] [Cross Ref]

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