Predictive Value of Anatomical Findings and Karyotype Analysis in the Diagnosis of Patients with Disorders of Sexual Development

Abstract

We assessed the predictive value of anatomical findings and karyotype for establishing a diagnostic orientation in patients with disorders of sex development (DSD). We performed a retrospective chart analysis of 228 patients, grouped into 4 categories: 46,XX DSD, non-dysgenetic testicular DSD, dysgenetic testicular DSD and ovotesticular DSD. Degree of virilisation, presence of vagina, presence of palpable gonads, size of gonads and a plain karyotype was available for all cases. 46,XX DSD due to congenital adrenal hyperplasia counted for 59.2% of the cases, non-dysgenetic testicular DSD for 13.6%, dysgenetic testicular DSD for 21.5% and ovotesticular DSD for 5.7%. Excluding congenital adrenal hyperplasia (CAH), a karyotype with at least one 46,XX cell line had a high diagnostic efficiency for ovotesticular DSD. In these patients, anatomical findings were not as useful to predict the gonadal phenotype. The existence of a 45,X cell line predicted with very high efficiency dysgenetic testicular DSD. Genital palpation was only partially helpful to predict the existence of testicular tissue. Non-dysgenetic testicular DSD could be ruled out with high efficiency in patients with an abnormal karyotype. Anatomical findings were helpful in 46,XY patients: palpated masses predicted non-dysgenetic testes with high accuracy. In all cases assessment of gonadal volume was less useful.

Pediatric disorders of sex development

“…9,10 Arcari et al documented 46XY (dysgenetic and non-dysgenetic) DSD in 34.7% of the patients. 11 No case of mosaicism was detected. The policy of screening only 20 metaphases may not be sufficient to detect of low grade (<5%) mosaicism.…”

“…Ovotesticular DSD was reported in 5.7%, 4.8% and 14.3% of the cases by Arcari et al, Nimkarn et al and Rajendran et al respectively which was in contrast to a solitary patient in our cases. 6,10,11 CAH and gonadal dysgenesis were the commonest etiology for DSD. Most authors across the world have documented similar results.…”

Spreading the Clinical Window for Diagnosing Fetal-Onset Hypogonadism in Boys

“…The need for a differential diagnosis between testicular dysgenesis (i.e., whole gonadal dysfunction) and a specific steroidogenic failure emerges. A few clinical signs can be helpful in certain cases: the existence of two palpable gonads >1 mL is highly indicative of non-dysgenetic DSD (75), whereas the association of syndromic phenotypes – like skeletal dysplasia, macro/microcephaly, cardiac or renal defects, thalassemia, mental retardation, or minifascicular neuropathy orientate to gonadal dysgenesis (Table 2). Skeletal dysmorphisms may be present in patients with POR deficiency associated with the Antley–Bixler syndrome.…”

Factors That Influence the Decision to Perform a Karyotype in Suspected Disorders of Sex Development: Lessons from the Scottish Genital Anomaly Network Register

“…Indeed, the primary root of the new DSD nomenclature is based on the karyotype [Hughes et al, 2006]. Although there are a number of reports of karyotyping in infants with genital anomalies, these studies were either performed to assess the prevalence of genetic abnormalities in such cases, or to assess the value of anatomical findings in predicting the likelihood of an abnormal karyotype [Rajfer and Walsh, 1976;Rohatgi et al, 1987;McAleer and Kaplan, 2001;Arcari et al, 2007]. There are currently no reports on the proportion of children routinely presenting with genital anomalies who were karyotyped and the clinical factors that influence the clinician in reaching a decision to perform a karyotype.…”