Limb disorders

Gene: CRIPT

Green List (high evidence)

Comment on list classification: There are now 6 unrelated individuals reported in literature with biallelic CRIPT variants and Rothmund-Thomson syndrome, with toe syndactyly being a consistent feature. In addition, one patient had a proximally placed thumb, and all 6 had feet abnormalities including pes planus, pes calcaneovalgus, and skewfoot. Hence, this gene can be promoted to Green at the next update.

Created: 11 Sep 2026, 11:04 a.m. | Last Modified: 11 Sep 2026, 11:04 a.m.

Panel Version: 9.6

PMID: 37013901 Averdunk et al., 2023
Report of 2 probands diagnosed with Rothmund-Thomson syndrome, harbouring biallelic CRIPT variants.
P1 - 4yo Moroccan female, homozygous for CRIPT: c.132del, p.Ala45Glnfs*86
P2 - 8yo Romanian male homozygous for CRIPT: c.227G>A, p.(Cys76Tyr)
Both patients had facial rash, poikiloderma, sparse hair, short stature, syndactyly of toes, feet abnormalities, seizures, abnormal teeth, developmental delay, recurrent chest infections; P1 also had cataracts, dystrophic nails, and a proximally placed thumb; only P2 had microcephaly.

Also includes literature review of previously reported patients (PMID: 36630262 Akalın et al., 2023; PMID: 27250922 Leduc et al., 2016; PMID: 24389050 Shaheen et al., 2014) - 4 unrelated probands with unique biallelic CRIPT variants: hmz c.133_134insGG, p.(Ala45Glyfs∗82); hmz c.141del p.(Phe47Leufs∗84); comp het c.8G>A p.(Cys3Tyr) & 1,331 bp del exon 1; hmz c.7_8del; p.(Cys3Argfs∗4).
2 individuals were from Saudi Arabia, one from Turkey, and one African American.
Phenotype: facial rash (3/4), poikiloderma (2/4), short stature (4/4), sparse hair (3/4), Osteopenia/metaphyseal striations (4/4), dystrophic nails (1/4), syndactyly of toes 4&5 (4/4), proportional microcephaly (4/4), dev delay (4/4), recurrent chest infections (4/4), anemia (3/4), variable retinal defects (4/4), abnormal teeth (2/4), scoliosis (4/4), 11 pairs of ribs (2/4), feet anomalies including pes planus, pes calcaneovalgus, and skewfoot |(4/4).
None of the patients had cataracts.
Microcephaly severity: PMID: 27250922 head circumference was 47 cm (Z=−2.7) at 4 yrs. PMID: 24389050: individuals had head circumference of 45 cm (-2.5SD) and 35 cm (-2.7 SD) respectively at time of report. PMID: 36630262 - proband OFC was 44cm at last evaluation (-4.63 SDS).
Sources: Literature

Created: 11 Sep 2026, 10:54 a.m. | Last Modified: 11 Sep 2026, 11:04 a.m.

Panel Version: 9.6

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Rothmund-Thomson syndrome, type 3, OMIM:615789; Rothmund-Thomson syndrome type 3, MONDO:0014347

Publications

• 24389050
• 27250922
• 36630262
• 37013901