Ectodermal dysplasia

Gene: RECQL4

Green List (high evidence)

Comment on list classification: There are numerous patients reported in literature with biallelic RECQL4 variants and Rothmund-Thomson syndrome, with ectodermal dysplasia being a consistent feature (primarily manifesting in poikiloderma, sparse hair/alopecia, sparse eyebrows and eyelashes, sometimes hypoplastic teeth / microdontia). Based on available evidence, this gene can be promoted to Green at the next update.

Created: 11 Sep 2026, 4:17 p.m. | Last Modified: 11 Sep 2026, 4:17 p.m.

Panel Version: 5.9

PMID: 41628607 Genç et al., 2026
Report of 4 patients with Rothmund-Thomson syndrome who were homozygous for c.2415_2419del (p.Gly806_Arg807delinsTer) and 2 sibs comp het for c.1663_1664del (p.Ser555GlyfsTer27) and the same p.Gly806_Arg807delinsTer variant - likely Turkish founder variant, all families are from the same region. All patients exhibited poikiloderma, facial telangiectasia, skin atrophy, growth retardation, microcephaly, and learning difficulties.

PMID: 40031098 Ho et al., 2025
F1 - Chinese female proband; pregnancy was complicated by IUGR, oligohydramnios, and maternal pre-eclampsia; she had head circumference of 41cm (-3.19 SDS) and height of 59cm (-5.4 SDS) at 11 months old. She also presented with dysplastic nails, borderline dev delay, palmoplantar keratoderma, facial rash, sparse eyebrows and eyelashes, hypo- and hyper-pigmented skin lesions on her legs. She was diagnosed with osteosarcoma at 13 yo. Her younger sister was similarly affected.
WES revealed biallelic RECQL4 variants c.1704+2T>C and p.Arg755Gln.
F2 - Chinese male proband; he presented in infancy with an erythematous rash on sun-exposed areas; skin biopsy was consistent with poikiloderma; he had normal development, sparse eyebrows, normal head circumference and height at 22 months. He was diagnosed with osteosarcoma at 6 years old.
WES detected biallelic RECQL4 variants c.2059-1G>A and p.Glu918*.

PMID: 39324487 Kanai et al., 2025
Two Japanese cases with a severe phenotype and biallelic RECQL4 variants.
P1 - male fetus with severe structural abnormalities, pregnancy was terminated at 21+2 weeks; he harboured biallelic RECQL4 variants c.1390+1G>C and c.1048_1049del, p.Arg350Glyfs*21 (confirmed in trans by WES).
P2 - female infant with height of 28.5cm (-7.7 SD) and head circumference of 27cm (-4.4 SD) at birth; she had digital and skeletal anomalies, and died just after birth due to respiratory insufficiency. She was biallelic for a RECQL4 deletion of exons 12-18 (trio exome).

PMID: 38021400 Martins et al., 2023
Literature review of Rothmund-Thomson syndrome cases. 49 individuals with RECQL4 variants from 43 families are included. While short stature is noted in 34/43 patients, severity is not stated. Microcephaly is marked as 'not reported'.
Ectodermal dysplasia findings: Poikiloderma (generalized) in 41/43 patients, Sparse hair/eyebrows and/or eyelashes noted in 29/43, and nail dysplasia was seen in 4/7 assessed probands.

PMID: 27247962 Suter et al., 2017
Study analysed 43 patients with suspicion of Rothmund–Thomson syndrome and identified 23 different RECQL4 mutations in 18 individuals. Targeted PCR sequencing of RECQL4 was used.
Clinical details are available for 12 patients with biallelic RECQL4 variants: poikiloderma (9/12), characteristic cutaneous rash (5/12), photosensitivity (2/12), alopecia (4), spare eyebrows/eyelashes (6), teet abnormalities (hypoplastic teeth, microdontia - 3 patients), linear growth deficiency/microsomia (8), variable skeletal anomalies (9/12), delayed development (4), low birth weight / failure to thrive (5); 2 were diagnosed with cancer, one with osteosarcoma at 2 yo. Microcephaly not mentioned.
Sources: Literature

Created: 11 Sep 2026, 4:15 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Rothmund-Thomson syndrome, type 2, OMIM:268400; Rothmund-Thomson syndrome type 2, MONDO:0016369

Publications

• 38021400
• 39324487
• 40031098
• 41628607