Ectodermal dysplasia

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 features of ectodermal dysplasia. 5/6 probands had sparse hair or alopecia, abnormal teeth were reported in four patients (e.g., conic, delayed), and dystrophic nails were reported in two. Hence, this gene can be promoted to Green at the next update.

Created: 11 Sep 2026, 11:08 a.m. | Last Modified: 11 Sep 2026, 11:08 a.m.

Panel Version: 5.7

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, 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).
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.

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