Genetics of Sex and Differences of Sex Development (DSD)

Vocabulary practice flashcards covering the chromosomal, genetic, hormonal, and anatomical foundations of sex development, differences of sex development (DSD), and their clinical relevance to speech-language pathology and audiology.

Turner syndrome (45,X)

A condition resulting from a missing second sex chromosome that occurs in 1 in 2000 births; individuals present phenotypically female with preserved overall intelligence despite potential cognitive impacts, and it carries high audiological relevance due to middle-ear disease and progressive sensorineural hearing loss.

45,X/46,XY mosaicism

A chromosomal mosaicism occurring in approximately 1 in 6000 individuals that can result in mixed gonadal dysgenesis, atypical sex differentiation, ambiguous or variable genitalia, and intersex characteristics.

Klinefelter syndrome (XXY)

A sex chromosome variation occurring in 1 in 660 males with male internal and external anatomy, characterized by hypogonadism, variable pubertal development, gynecomastia, and speech-language characteristics including language delays, phonological processing difficulties, and social pragmatic differences.

SRY gene

A sex-determining gene located on the short arm of the Y chromosome at locus Yp11.2 that directs male testicular differentiation.

CYP21A2 gene

A gene located at locus 6p21.33 that codes for an enzyme essential to adrenal function (production of hormones, steroids, fats, and cholesterol); mutations occur in 1 in 1000 individuals and can cause adrenal hyperplasia and excess male hormones.

AR gene

The gene encoding the androgen receptor; it is essential for male differentiation and influences bone density, muscle development, puberty, red blood cell production, and sexual desire and function across all genders.

Androgen insensitivity syndrome (AIS)

A condition occurring in approximately 5 in 100,000 individuals, most commonly in 46,XY karyotypes, caused by AR gene mutations that impair cellular responsiveness to androgens, resulting in female, intersex, or male phenotypes.

SRD5A2 gene

A gene located at locus 2p23.1 that encodes 5α-reductase type 2, the enzyme responsible for converting testosterone into dihydrotestosterone (DHT); mutations can impair male secondary sex characteristic development in males and are associated with hirsutism and polycystic ovary syndrome in females.

Dihydrotestosterone (DHT)

A potent androgen converted from testosterone by the enzyme 5α-reductase type 2 (coded by SRD5A2) that mediates the development of male sex characteristics.

Differences of sex development (DSD)

The current, medically accurate terminology used to describe congenital conditions involving atypical chromosomal, gonadal, or anatomical sex differentiation, replacing imprecise and stigmatizing historical terms.

Persistent Müllerian duct syndrome (PMDS)

A condition in which a genetic male develops female internal reproductive structures in addition to male reproductive organs, associated with mutations in the AMH (locus 19p13.3) or AMHR2 (locus 12q13.13) genes.

Müllerian ducts

Embryonic duct structures present in bipotential gonads that regress during male development but differentiate into the uterine tubes and uterus during female development.

Wolffian ducts

Embryonic duct structures present in bipotential gonads that degrade during female development but develop into the epididymis and ductus (vas) deferens during male development.

SOX9

A transcription factor gene that serves as a major regulator of testicular differentiation downstream of SRY.

WNT4

A gene important in ovarian differentiation and the regulation of testicular developmental pathways.

RSPO1

A gene that supports ovarian development via WNT/β-catenin signaling.

NR5A1 (SF-1)

A nuclear receptor gene that regulates gonadal development and steroidogenesis, associated with variable DSD phenotypes in both 46,XY and 46,XX individuals.

WT1

A gene important in urogenital development and associated with clinical renal-gonadal conditions.

DHH

A gene involved in testicular development and certain forms of gonadal dysgenesis.

HSD17B3

A gene critical for testosterone synthesis whose deficiency causes 46,XY differences of sex development.

Puberphonia

A functional voice disorder characterized by the failure of the voice pitch to transition to an adult fundamental frequency during puberty.

Fundamental frequency ($F_0$)

The habitual pitch of the vocal cords, which decreases under the influence of testosterone-mediated laryngeal framework growth and vocal-fold thickening.

Hirsutism

Excessive growth of terminal body and facial hair in females, which can be linked to androgen excess or variations in steroidogenic genes such as SRD5A2.

Turner syndrome audiological surveillance protocol

Recommended hearing monitoring comprising newborn hearing screening, audiometry every 2–3 years starting at ages 1–2, annual tympanometry through age 5, annual childhood otoscopy, and audiometry every 5 years in adulthood.

Gender-affirming voice and communication therapy

Clinical intervention targeting acoustic parameters such as fundamental frequency ($F_0$), vocal resonance, prosody, and communication participation to improve quality of life and vocal satisfaction.