Monogenic short stature

Gene: ANAPC1

Red List (low evidence)

PMID: 42210937 Huang et al., 2026
Report of a milder case of a 29-year-old man who presented with lifelong sparse, fine scalp hair, bilateral malar erythema, soft fingernails, and dental anomalies (malocclusion with multiple caries). WES identified a heterozygous ANAPC1 (NM_022662.4:c.4907T>C, p.Val1636Ala) variant - 13 hets reported in gnomAD v4 (East Asian pop).

PMID: 38021400 Martins et al., 2023
Literature review of Rothmund-Thomson syndrome cases. 11 individuals with biallelic ANAPC1 variants from 8 families are included. While short stature is noted in 7/11 patients, severity is not stated. Microcephaly is marked as 'not reported'.
Ectodermal dysplasia findings: Poikiloderma (generalized) in 11/11 patients, Sparse hair/eyebrows and/or eyelashes noted in 10/11, and nail dysplasia was seen in 5/11 assessed probands.
10 individuals had juvenile cataracts. Growth hormone deficiency was diagnosed in 5/10 probands.

Created: 11 Sep 2026, 4:33 p.m. | Last Modified: 11 Sep 2026, 4:40 p.m.

Panel Version: 2.9

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Rothmund-Thomson syndrome, type 1, OMIM:618625; Rothmund-Thomson syndrome type 1, MONDO:0016368

Publications

• 31303264
• 35664819
• 38021400
• 42210937

I don't know

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

Created: 3 Mar 2022, 1:49 p.m. | Last Modified: 3 Mar 2022, 1:49 p.m.

Panel Version: 1.100

This gene is associated with a relevant phenotype in OMIM and Gene2Phenotype. PMID: 31303264 describes 10 patients from 7 families with Rothmund-Thomson syndrome. 4 of 7 families are homozygous for the same intronic variant (c.2705-198C-T) and the remaining 3 affected families are compound heterozygous (c.2705-198C-T with another variant in the gene). Affected individuals from families who are compound heterozygous have growth retardation. There is enough evidence to support a gene-disease association. However, this gene should be reviewed at the next panel update to see if this should be rated Green.
Sources: Literature

Created: 11 Dec 2020, 4:23 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Rothmund Thomson syndrome type 1, OMIM:618625, MONDO:0016368

Publications

• 31303264