Nongenital malformation syndromes in patients with disorders of sex development (DSDs) can be classified into two subtypes
In the first subtype, patients have abnormalities of hormonal function; in the second subtype, they have normal sex hormones but have a primary morphological defect of genital development
So-called nonhormonal morphological syndromes can be recognised by the presence of abnormal anatomy beyond a narrow range of external genital structures on a spectrum between normal male anatomy through to normal female anatomy
The genetic causes of many hormonal DSDs with malformation syndromes are now often known
Many nonhormonal DSDs with morphological changes do not have known genetic causes, but expected advances in the field are likely to change this situation in the future
When embryological development of the internal and/or external genitalia is disrupted, the patient presents with a disorder of sex development (DSD) in the neonatal period or sometime later in life. Some of these patients have other, nongenital malformations, which makes their overall management more complex than if they just had a DSD. This Review summarises these malformation syndromes and discusses the recent research into their aetiology. The genetic causes of these malformation syndromes, when they are known, will also be described. Many specific genetic mutations are now known in malformation syndromes with a defect in hormonal function. By contrast, the genetic causes remain unknown in many nonhormonal morphological anomalies that affect the genitalia.
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Syndromic disorder of sex development due to a novel hemizygous mutation in the carboxyl-terminal domain of ATRX
Human Genome Variation Open Access 13 April 2017
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Hutson, J., Grover, S., O'Connell, M. et al. Malformation syndromes associated with disorders of sex development. Nat Rev Endocrinol 10, 476–487 (2014). https://doi.org/10.1038/nrendo.2014.83
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