RECQL4 – Rapadilino syndrome

Rapadilino syndrome is an autosomal recessive disorder characterized by radial ray hypoplasia/aplasia, patellar anomalies, cleft or highly arched palate, slender nose, and growth deficiency. Biallelic pathogenic variants in RECQL4 have been reported in 3 unrelated probands with Rapadilino syndrome, including the recurrent c.3061C>T (p.Arg1021Trp) variant (PMID:15897384; PMID:23899764; PMID:26064716). No segregation beyond the probands has been documented, and no large cohort studies are available.

Functional assays of the canonical splice-site mutation c.1390+2del demonstrate in-frame skipping of exon 7, resulting in loss of a conserved nuclear retention domain and abolishment of helicase and ATPase activities (PMID:17250975; PMID:22885111). These findings support a loss-of-function mechanism via impaired DNA replication and repair. Key take-home: RECQL4 mutation analysis is recommended for patients with Rapadilino features to inform diagnostic, counseling, and potential DNA repair–targeted therapies.

References

• Archives of dermatology | 2005 | A patient with Rothmund-Thomson syndrome and all features of RAPADILINO. PMID:15897384
• Dermatology (Basel, Switzerland) | 2013 | Long-term follow-up and molecular characterization of a patient with a RECQL4 mutation spectrum disorder. PMID:23899764
• Case reports in immunology | 2015 | Immunodeficiency in a Child with Rapadilino Syndrome: A Case Report and Review of the Literature. PMID:26064716
• Gene | 2007 | Nuclear import and retention domains in the amino terminus of RECQL4. PMID:17250975
• Biochimica et biophysica acta | 2012 | RAPADILINO RECQL4 mutant protein lacks helicase and ATPase activity. PMID:22885111

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