Vascular-type disruptive defects in fetuses with homozygous α-thalassemia: Report of two cases and review of the literature

Margaret P. Adam, Jane Chueh, Yasser Y. El-Sayed, Ana Stenzel, Hannes Vogel, David D. Weaver, H. Eugene Hoyme

Research output: Contribution to journalArticle

16 Scopus citations


Background: The thalassemias are an inherited group of heterogeneous anemias in which one or more of the globin chains in the hemoglobin tetramer are absent. Fetuses with homozygous α-thalassemia, which is particularly prevalent in people of Southeast Asian extraction, experience deficient α-globin chain synthesis and cannot produce hemoglobin F (the primary fetal hemoglobin after 8 weeks' gestation). Instead, they produce an anomalous hemoglobin, hemoglobin Bart's, with an unusually high affinity for oxygen, leading to profound anemia and tissue hypoxia. Methods and Results: Here we report on two fetuses with homozygous α-thalassemia who displayed structural defects of a vascular disruptive type. Both fetuses demonstrated limb anomalies, including terminal transverse limb deficiencies, and one fetus was found to have a brain malformation consisting of a neuronal migrational defect. The limb anomalies and suspected brain malformation were detected on prenatal ultrasound prior to confirmation of the diagnosis of α-thalassemia in one case; in the other case prenatal records were not available. While microcephaly, hydrocephalus, and retarded brain growth have been rarely reported in association with homozygous α-thalassemia, this is the first report of a true brain malformation in an affected fetus. Limb anomalies, on the other hand, appear to be more frequent. Recently, aggressive in utero and postnatal therapies for homozygous α-thalassemia have been attempted with some success. Conclusions: Our cases and those from the medical literature suggest that couples need to be counseled about the risks of congenital anomalies of a vascular disruptive type in affected fetuses. Furthermore, data from the literature suggests that in utero therapy may not significantly decrease these risks as such anomalies may be present prior to the institution of therapy. In addition, in hydropic infants with vascular disruptive defects, especially in those of Southeast Asian origin, homozygous α-thalassemia should be suspected as a likely etiology.

Original languageEnglish (US)
Pages (from-to)1088-1096
Number of pages9
JournalPrenatal Diagnosis
Issue number12
StatePublished - Dec 1 2005


  • α-thalassemia
  • Brain malformations
  • Limb reduction defects
  • Neuronal migrational defects

ASJC Scopus subject areas

  • Genetics(clinical)
  • Obstetrics and Gynecology

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