Maternal uniparental disomy for chromosome 6 in a patient with IUGR, ambiguous genitalia, and persistent mullerian structures

Fetal sex development consists of three sequential stages: a) the undifferentiated stage, when identical primitive structures develop in the XY and XX embryos, b) gonadal differentiation into testes or ovaries, and c) the differentiation of internal and external genitalia, which depends on the action of testicular hormones. Disorders of sex development (DSD) may result from defects in any of these stages. Abnormal formation of the anlagen of internal and/or external genitalia in early embryonic development results in Malformative DSD. In patients with a Y chromosome, defects in testis differentiation drive to early-onset fetal hypogonadism affecting whole testicular function, a condition named Dysgenetic DSD. In Non-dysgenetic DSD, the underlying pathogenesis may involve early-onset fetal hypogonadism affecting specifically either Leydig or Sertoli cell function, or male hormone end-organ defects in patients devoid of fetal hypogonadism. Understanding the pathogenesis is useful for an efficient early diagnosis approach, which is necessary for adequate decision making in the management of DSD. Copyright © 2010 Elsevier Ltd. All rights reserved.

Study Type--Therapy (case series) Level of Evidence 4. What's known on the subject? and What does the study add? Approximately 200 cases of persistent Müllerian duct syndrome have been reported over the last 50 years and most authors suggest leaving the Müllerian remnant in situ because of the difficulty in dissection and the presumed absence of risk of malignancy. However, with increasing reports of Müllerian malignancies emerging, we report our 10-year experience of managing patients with persistent Müllerian duct syndrome, with removal of müllerian remnants. This case series shows that there is an increased risk of Müllerian malignancy that was previously unknown. With the laparoscopic approach, orchidopexy with simultaneous removal of Müllerian remnants could be accomplished with minimal surgical trauma and the benefit of no malignancy risk in the future. This is a new technique that has not been previously performed. Considering the current evidence of malignancy in the Müllerian remnant, surgeons would need to discuss with families about removal of remnants or long-term monitoring.

To review all cases with segmental and/or complex uniparental disomy (UPD) and to discuss the impact of these cases on medical genetics. Searching for published reports in PubMed and in the abstract books of the annual meetings of the American Society of Human Genetics and the European Society of Human Genetics up to March 2008. In total, 26 cases with segmental UPD and a normal karyotype, 38 cases with UPD of a whole chromosome and a simple reciprocal or non-homologous Robertsonian translocation, four cases each with two isochromosomes and UPD of the short arm isochromosome and opposite UPD of the long arm isochromosome, three cases with UPD and an isochromosome of the short arm and the long arm of a metacentric or a submetacentric chromosome, one case with maternal UPD and an isochromosome 8 associated with a homozygous deletion (8)(p23.3pter), 42 cases with UPD and an isochromosome of the long arm of an acrocentric chromosome, 33 cases with UPD and a supernumerary marker or ring chromosome, 17 cases with UPD of a whole or parts of a chromosome and a complex karyotype, 13 cases with most likely mosaicism for genome wide paternal UPD, and three cases with most likely mosaicism for genome wide maternal UPD were found. This update shows that, in particular, the number of reported cases with segmental UPD or UPD associated with a marker chromosome clearly increased within the last few years, and that the investigation of both parents in cases with homozygosity of an autosomal recessively inherited mutation in some cases might help improve genetic counselling, resulting in a reduced recurrence risk in the case of UPD. Moreover, cases with segmental or complex UPD show that meiosis and early postzygotic mitoses seem to be more complex events than previously thought. For the formation of all kinds of segmental or complex UPD or genome wide UPD mosaicism, always a fortunate co-occurrence of meiotic or mitotic recombination, abnormal segregation, and subsequent correction are necessary. No case of recurrence has been reported until now. Therefore, in subsequent pregnancies invasive prenatal diagnosis is not necessarily indicated.