Severe microcephaly

Gene: PDCD6IP

Green List (high evidence)

Comment on list classification: There are now 2 unrelated probands with severe microcephaly (1 progressive post-natally). A supportive mouse model recapitulating microcephaly is also available (PMID: 28322231, old gene name Alix). Hence, this gene can now be promoted to Green.

Created: 13 Aug 2026, 4:29 p.m. | Last Modified: 13 Aug 2026, 4:31 p.m.

Panel Version: 9.17

Comment on phenotypes: OMIM phenotype updated 13th Aug 2026.

Created: 13 Aug 2026, 4:27 p.m. | Last Modified: 13 Aug 2026, 4:27 p.m.

Panel Version: 9.17

PMID: 40897677 D'Alessio et al., 2025
Report of a male individual with mild intellectual disability and acquired microcephaly carrying a homozygous nonsense variant in PDCD6IP: NM_013374.6 c.964C>T p.(Arg322*). Heterozygous family members unaffected. Additional features of strabismus and thrombocytopenia was also noted. No seizures present. Proband OFC listed as 52.7cm (−2.5 SD) in table 1. At birth, his OFC was 34 cm (−0.78 SD), but at age 25 yrs, his OFC was 51.6 cm (−3.1 SD).

Created: 13 Aug 2026, 4:25 p.m. | Last Modified: 13 Aug 2026, 4:26 p.m.

Panel Version: 9.15

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
?Microcephaly 29, primary, autosomal recessive, OMIM:620047; microcephaly 29, primary, autosomal recessive, MONDO:0031060

Publications

• 28322231
• 32286682
• 40897677

Comment on list classification: Phenotype is relevant to this panel with a supportive animal model that recapitulates features such as microcephaly. However, additional cases required to validate pathogenicity prior to inclusion as diagnostic-grade. Therefore Rating Amber, awaiting further publications.

Created: 4 Jun 2021, 12:21 p.m. | Last Modified: 4 Jun 2021, 12:21 p.m.

Panel Version: 2.202

I don't know

One consanguineous family with 2 affected sibs with primary microcephaly (-4SD), intellectual disability and short stature (-5/6SD), and homozygous frameshift variant in PDCD6IP. The homozygous variant was confirmed in both affected sibs, while the four healthy siblings and parents were heterozygous. The clinical features observed in the patients were similar to the phenotypes observed in mouse and zebrafish models of PDCD6IP mutations in previous studies. Borderline Red/Amber rating in view of the supportive animal model data.
Sources: Expert list

Created: 3 Sep 2020, 1:51 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Primary microcephaly

Publications

• 32286682