The External Genitalia Score (EGS): A European Multicenter Validation Study

Abstract

Context Standardized description of external genitalia is needed in the assessment of children with atypical genitalia. Objectives To validate the External Genitalia Score (EGS), to present reference values for preterm and term babies up to 24 months and correlate obtained scores with anogenital distances (AGDs). Design, Setting A European multicenter (n = 8) validation study was conducted from July 2016 to July 2018. Patients and Methods EGS is based on the external masculinization score but uses a gradual scale from female to male (range, 0–12) and terminology appropriate for both sexes. The reliability of EGS and AGDs was determined by the interclass correlation coefficient (ICC). Cross-sectional data were obtained in 686 term babies (0–24 months) and 181 preterm babies, and 111 babies with atypical genitalia. Results The ICC of EGS in typical and atypical genitalia is excellent and good, respectively. Median EGS (10th to 90th centile) in males < 28 weeks gestation is 10 (8.6–11.5); in males 28–32 weeks 11.5 (9.2–12); in males 33–36 weeks 11.5 (10.5–12) and in full-term males 12 (10.5–12). In all female babies, EGS is 0 (0-0). The mean (SD) lower/upper AGD ratio (AGDl/u) is 0.45 (0.1), with significant difference between AGDl/u in males 0.49 (0.1) and females 0.39 (0.1) and intermediate values in differences of sex development (DSDs) 0.43 (0.1). The AGDl/u correlates with EGS in males with typical genitalia and in atypical genitalia. Conclusions EGS is a reliable and valid tool to describe external genitalia in premature and term babies up to 24 months. EGS correlates with AGDl/u in males. It facilitates standardized assessment, clinical decision-making and multicenter research.

Pubertal development in 46,XY patients with NR5A1 mutations

“…Additionally, our data demonstrate that pubertal development does not strongly correlate to the degree of virilization of the external genitalia at birth in 46,XY DSD caused by NR5A1 mutations. All patients who presented in early infancy had very low External Genitalia Scores ranging from 3.5 to 5.5 (EGS in male babies (0-1 months, > 37th weeks of gestation, birth weight 2500-4000 g) with typical genital phenotypes: median = 12, 10th percentile = 10.5, and 90th percentile = 12 [33]). Therefore, several patients were first assigned female after birth but soon reassigned as male due to further evaluation.…”

“…In patients 1-4, ambiguous genitalia with signs of undervirilization and significantly reduced external genitalia scores (EGS; normal > 10.5 [33]) were noticed at birth with a median EGS of 4.3 (range 3.5-5.5). Patient 5 showed a clitoromegaly and rugated labioscrotal folds at birth but EGS in this patient as well as in patient 6 could not be calculated due to insufficient phenotypic information.…”

Serum Concentrations and Gonadal Expression of INSL3 in Eighteen Males With 45,X/46,XY Mosaicism

“…In all patients, the karyotype was verified through medical records. Clinical data extracted from medical records included information on; 1) external genital phenotype at time of diagnosis, scored according to the External Genitalia Score (EGS) ranging from 0-12 points, with increasing scores indicating increasing degrees of androgenization ( 26 ); 2) spontaneous pubertal onset (yes, no); 3) type of testosterone treatment (transdermal, intramuscular, none) if the patient was substituted with testosterone at the time of blood sampling; 4) gonadal surgery (biopsy, gonadectomy); and 5) semen analysis (azoospermia, concentration).…”

ENDO-ERN expert opinion on the differential diagnosis of pubertal delay

“…In boys, the presence of neonatal cryptorchidism (particularly the bilateral forms) and micropenis are important findings, pointing to a prenatal and postnatal gonadotropin deficiency. All boys with an underdeveloped (at least 2.5 SD below the mean) but otherwise normal penis, without hypospadias, should be further investigated to exclude CHH, based on baseline assessment of the HPG axis during minipuberty (~1–4 months after birth), or an HCG stimulation test thereafter, due to the physiological reduction of gonadotropins until puberty [ 2 , 21 ]. More complex forms of genital under-virilization are more likely due to hypergonadotropic hypogonadism rather than CHH [ 6 , 22 ].…”