Monogenic short stature

Gene: PPP2R3C

Green List (high evidence)

There are now several unrelated probands with biallelic PPP2R3C variants and syndromic gonadal dysgenesis. Retardation of bone age is a consistent feature of this disorder. At least 3 unrelated individuals have been reported with severe short stature of -3 to -4.1 SD below mean (measured at age 2 years or above). Hence, this gene can be promoted to Green on Monogenic short stature.

Created: 26 Oct 2026, 6:33 p.m. | Last Modified: 26 Oct 2026, 6:33 p.m.

Panel Version: 2.13

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. 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.

PMID: 34750818 - 8 patients with gonadal dysgenesis from 4 unrelated families of Turkish and Indian descent, with 3 different homozygous PPP2R3C variants and gonadal dysgenesis. Short stature was a consistent finding, though no severity given. Growth hormone deficiency was reported in 1 family.

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.
P1 was 110.2 cm tall (−4.1 SDS) at 9 years.
P2 at 10 yrs was 133.7 cm tall (−1.13 SDS).

PMID: 30893644 - Four Turkish female probands from four unrelated families with 46, XY complete gonadal dysgenesis and three different homozygous PPP2R3C variants.
P1 was 87.5 cm tall (50–75%) at 2 yo.
P2 was 112.6 cm tall (<3%) at 9yo.
P3 - her height was between -2.5 and −3 SDS before estradiol therapy, and was was at a final
height of 161 cm tall (25–50%) at 19 yrs.
P4 - at 1 year old, she was 67 cm tall (<3%).

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

Created: 26 Oct 2026, 6:24 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

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

Publications

• 30893644
• 34714774
• 34750818
• 35812758