Assessing sex assignment concordance with genotype and phenotype

Abstract

ObjectivesTo catalogue patients with DSD and to assess the concordance of genotype and phenotype with sex assignment at birth compared to sex assignment before and following assessment by a Gender Medicine Team (GMT) at one institution, as an initial step in formulating standardized guidelines for management of these conditions.DesignAfter obtaining IRB approval, a retrospective chart review was conducted patients seen in the Gender Medicine Clinic (GMC) between 2006–2009 at Texas Children’s Hospital (TCH), Houston, Texas. McNemar’s test and Kappa agreement provided associations of various factors with sex assignment at birth prior to GMT assessment and after GMT assessment.ParticipantsForty-seven patients seen in the GMC with confirmed DSD.ResultsForty-seven patients met the inclusion criteria. The mean age of the patients at the time of GMT evaluation was 9.1+/−6.1 years; 61.7% had male karyotype, and 38.3% had female karyotype; 51.1% had a male external phenotype, 42.6% had a female external phenotype, and 6.4% had phenotypic ambiguity. Sex assignment was concordant with genotype and phenotype in 63.8% and 86.4%, respectively of cases at the time of birth and in 76.6% and 97.7%, respectively, of cases after assessment by GMT.ConclusionLong-term outcomes are needed to establish standardized practice guidelines for decision-making.

The Clinical Manifestation and Genetic Evaluation in Patients with 45,X/46,XY Mosaicism

“…Several factors are involved in this process, but the degree of virilization of the external genitalia and the presence of gonads with testicular features stand out among them [Suresh et al, 2013]. EMS could reflect both gonadal differentiation and the risk of tumors in patients with 45,X/46,XY mosaicism [Cools et al, 2009].…”

Disorders of sex development: advances in genetic diagnosis and challenges in management

“…43,44 The Chicago Consensus of 2005 stated that sex assignment cannot solely be based on genital appearance but should include consideration of the diagnosis, surgical options, need for lifelong replacement therapy, the potential for fertility, views of the family, and circumstances relating to cultural practices. 20 Although karyotype and external appearance of genitalia continue to be associated with the choice of assigned sex, 45 the results from a recent analysis of the International DSD (I-DSD) Registry revealed that the practice of assigning male sex in newborns with 46,XY DSD seems to be increasing. 46 This change in practice may be influenced by improvements in long-term surgical outcome in men with 46,XY DSD with conditions such as micropenis and potential for penile reconstruction or neophallus construction.…”

Gender identity, gender assignment and reassignment in individuals with disorders of sex development: a major of dilemma

“…The Chicago Consensus statement did not include specific diagnoses, but some consensus participants have provided more specific recommendations described here [80]. However, long-term outcomes are needed to establish standardized practice guidelines for decision making [81]. Moreover, timing of genital surgery should be also taken into account.…”