Genetic Epilepsy

Gene: MED12

Green List (high evidence)

7 female individuals (2 previously reported and 5 unpublished) reported with a clinical diagnosis of Hardikar syndrome (rare multiple congenital anomaly syndrome characterized by facial clefting, pigmentary retinopathy, biliary anomalies, hydronephrosis, and intestinal malrotation, but normal cognition). Exome sequencing identified de novo pathogenic nonsense and frameshift variants in MED12 in all 7 individuals. Evidence of extremely skewed XCI in all patients with informative testing. No functional assays. Note: pathogenic missense variants in MED12 associated with Opitz-Kaveggia syndrome, Lujan syndrome, Ohdo syndrome, and nonsyndromic intellectual disability, primarily in males.

Created: 14 Apr 2021, 8:12 a.m. | Last Modified: 14 Apr 2021, 8:12 a.m.

Panel Version: 0.7183

Mode of inheritance
Other

Phenotypes
Hardikar syndrome, MIM# 301068

Publications

• 33244166

Green List (high evidence)

- There's no clear geno-pheno correlation. Missense can cause any of the phenos (FGS1, LS, Ohdo and nonsyndromic ID; Charzewska 2018).
- de novo PTCs cause female-specific Hardikar syndrome, very skewed X inactivation (Li, 2020)

- Several affected female carriers have been reported: usually with milder clinical manifestation, several families showed skewed X-chr inactivation pattern in affected female carriers (Wang 2020). However some families had no correlation between clinical outcome and X-chr inactivation in the blood samples (Charzewska 2018, Prontera 2016).

Created: 23 Mar 2021, 4:42 a.m. | Last Modified: 23 Mar 2021, 4:42 a.m.

Panel Version: 0.6863

Mode of inheritance
X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)

Phenotypes
Ohdo syndrome, X-linked MIM#300895; Lujan-Fryns syndrome MIM#309520; Opitz-Kaveggia syndrome MIM#305450

Publications

• PMID: 33244166
• 32174975
• 30006928
• 27312080