Severe microcephaly

Gene: CEP63

Green List (high evidence)

Comment on list classification: There are now 2 unrelated families reported with biallelic nonsense CEP63 variants and Seckel syndrome, including severe microcephaly. This gene-disease association is supported by mouse studies, where CEP63 deficiency results in microcephaly. Hence, this gene can be promoted to Green at the next update.

Created: 23 Oct 2026, 10:47 a.m. | Last Modified: 23 Oct 2026, 10:47 a.m.

Panel Version: 9.41

PMID: 37017437 Pacheco et al., 2023
Report of a family with three siblings who are comp het for variants in CEP63, c.1125T>G, p.(Tyr375*) and c.595del, p.(Glu199Asnfs*11). Parents confirmed het for a variant each, unaffected. All siblings present with microcephaly and intellectual disability but only one has severe short stature. Head circumference at birth was -3.7 to -4.7 SD below mean for all 3 sibs. Seckel syndrome diagnosis.

PMID: 34068194 Makhdoom et al., 2021
Family 2 - consanguineous family with five affected members manifesting microcephaly of −11 to −15 SD and moderate ID. Affected individuals were homozygous for p.(Ser240Cysfs*16), in ASPM, and heterozygous for a c.1261A>T;p.(Thr421Ser) variant in CEP63.
An asymptomatic brother was het for both the ASPM variant and the CEP63 variant.
Authors pose that a heterozygous CEP63 variant aggravated the microcephaly and short stature severity phenotypes, caused by a biallelic ASPM mutation. ASPM is associated with Microcephaly 5, primary, autosomal recessive, OMIM:608716.

PMID: 21983783 Sir et al., 2011
First family described. Consanguineous Pakistani parents. Three family members had primary microcephaly at birth (head circumference −4SD to −6SD) and by five years showed mild/moderate mental retardation. To a lesser degree, they had proportionate short stature. "Mild Seckel syndrome" diagnosis. The affected individuals were homozygous for CEP63:c.129G>A, p.Trp43*. Functional studies detected some CEP63 protein in centrosomes of patient cells, implying the variant is hypomorphic.

Functional evidence: PMID: 26158450 - Marjanović et al., 2015 - CEP63 deficiency promotes p53-dependent microcephaly in mice - recapitulating Seckel syndrome seen in humans.

Created: 23 Oct 2026, 10:42 a.m. | Last Modified: 23 Oct 2026, 10:45 a.m.

Panel Version: 9.41

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
?Seckel syndrome 6 , OMIM:614728; Seckel syndrome 6, MONDO:0013871; SCKL6

Publications

• 21983783
• 26158450
• 34068194
• 37017437

The rating of this gene has been updated following NHS Genomic Medicine Service approval.

Created: 10 Mar 2022, 1:37 p.m. | Last Modified: 10 Mar 2022, 1:37 p.m.

Panel Version: 2.292

This gene has been tagged for review by the GMS specialist group.

Created: 5 May 2021, 2:09 p.m. | Last Modified: 5 May 2021, 2:09 p.m.

Panel Version: 2.128

I don't know

Only one family reported to date; functional evidence.

Created: 4 Sep 2020, 10:12 a.m. | Last Modified: 4 Sep 2020, 10:12 a.m.

Panel Version: 2.20

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Seckel syndrome 6, MIM#614728

Publications

• 21983783
• 26158450

I don't know

As discussed with the GMS Neurology Specialist Test Group webex call 11th July 2019: The Specialist Test Group all agreed that there is enough evidence to rate this gene Green

Created: 29 Jul 2019, 4:18 p.m. | Last Modified: 29 Jul 2019, 4:18 p.m.

Panel Version: 1.62

Green List (high evidence)

Mutations identified in three cousins from one family but gene known to be involved in centrosome function and good mouse model exists

Created: 11 Jan 2017, 3:11 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
?Seckel syndrome 6 614728

Publications

• 21983783
• 26158450