Paediatric disorders - additional genes

Gene: PPP2R3C

Green List (high evidence)

Comment on list classification: There are now several unrelated probands reported in literature with biallelic PPP2R3C variants and syndromic gonadal dysgenesis. Common features included facial dysmorphism, mild developmental delay, short stature and retardation of bone age. More variable features included hearing and vision impairment, myopathy, renal agenesis. Based on the early-onset syndromic presentation, PPP2R3C should be rated Green on Paediatric disorders - additional genes.

Created: 26 Oct 2026, 6:28 p.m. | Last Modified: 26 Oct 2026, 6:28 p.m.

Panel Version: 8.19

PMID: 35812758 Zhang et al., 2022
24yo Chinese female (46, XY) proband with complete gonadal dysgenesis (CGD) and biallelic PPP2R3C variants: p.F229del & p.G417E. Seq method: WES. She presented with poor development of secondary sexual characteristics and primary amenorrhea. She also had short stature (148 cm tall (-3SD) at 18 years old) and received growth hormone therapy.

Literature review from the paper: "Thirteen 46, XY DSD patients had been reported in three articles previously (Guran et al., 2019; Cicek et al., 2021; Altunoglu et al., 2022). All the patients came from consanguineous marriages and had homozygous PPP2R3C variants. Eleven out of thirteen 46, XY DSD patients presented with complete gonadal dysgenesis, complete female vulva with hypoplastic labium major, and hypoplastic uterus. Sex hormone levels were compatible with complete gonadal dysgenesis. One patient presented with partial testicular dysgenesis, and he had ambiguous genitalia, micropenis, and left cryptorchidism. Also, three 46, XX DSD patients presented with complete gonadal dysgenesis, recognizable facial features, and multiple extragenital malformations." Other features reported: facial dysmorphism (16/16), retardation of bone age (15/ 16), delayed development of the nervous system / mild neuromotor delay (14/16), and more variable features like SNHL, renal agenesis, myopathy, impaired vision. Intellect was mostly not reported, or noted to be 'low normal' - borderline ID.

PMID: 34750818 - 8 patients with gonadal dysgenesis from 4 unrelated families of Turkish and Indian descent, with 3 different homozygous PPP2R3C variants
PMID: 34714774 - 4 patients from 3 unrelated Turkish families with the same homozygous p.L193S variant in PPP2R3C - one 46,XX girl with primary gonadal insufficiency, two girls with 46,XY complete GD, and one undervirilised boy with 46,XY partial GD.
PMID: 30893644 - Four Turkish female probands from four unrelated families with 46, XY complete gonadal dysgenesis and three different homozygous PPP2R3C variants.

PPP2R3C is associated with AR Myoectodermal gonadal dysgenesis syndrome, OMIM:618419 (OMIM accessed 26th Oct 2026).

Created: 26 Oct 2026, 6:24 p.m. | Last Modified: 26 Oct 2026, 6:25 p.m.

Panel Version: 8.18

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Myoectodermal gonadal dysgenesis syndrome, OMIM:618419; gonadal dysgenesis, MONDO:0001967

Publications

• 30893644
• 34714774
• 34750818
• 35812758