TGM1 – Self-Healing Collodion Baby

Self-healing collodion baby (SHCB) is an autosomal recessive form of congenital ichthyosis characterized by a collodion membrane at birth followed by spontaneous resolution to normal or near-normal skin. Heterogeneity in causative genes has been described, with TGM1 implicated in a subset of cases alongside ALOX12B and ALOXE3. Recognition of SHCB is critical for prognosis, as patients avoid lifelong scaling and have generally favorable outcomes.

In two affected siblings from one family, compound heterozygous TGM1 missense variants c.832G>C (p.Gly278Arg) and c.1469A>G (p.Asp490Gly) were identified, both causing markedly reduced transglutaminase 1 activity and segregating in an autosomal recessive pattern ([PMID:12542526]). This family contributed two probands and two additional affected relatives sharing biallelic variants, confirming segregation.

A Scandinavian cohort of 15 SHCB patients revealed one additional TGM1 case among predominantly ALOX12B- and ALOXE3-mutated individuals, underscoring TGM1’s role across unrelated families despite its lower frequency in this phenotype ([PMID:19890349]).

A single new SHCB case report further detected a TGM1 mutation by targeted genetic testing, with clinical improvement following early supportive care and genetic confirmation facilitating counselling ([PMID:40193669]).

Functional studies combining molecular modeling and biochemical assays under elevated hydrostatic pressure demonstrated that the p.Asp490Gly substitution locks TGase 1 in an inactive trans conformation prenatally, with water chelation released postnatally allowing partial cis isomerization and restored activity, directly explaining the dynamic healing phenotype ([PMID:12542526]).

Collectively, 4 probands from 3 unrelated families, sibling segregation, and concordant functional data support a moderate clinical validity for TGM1 in SHCB. Inclusion of TGM1 in diagnostic ichthyosis panels enables accurate prognosis and management. Key take-home: TGM1 mutations can underlie a self-resolving collodion phenotype, highlighting the importance of early molecular diagnosis for tailored care.

References

• The Journal of investigative dermatology • 2003 • Self-healing collodion baby: a dynamic phenotype explained by a particular transglutaminase-1 mutation. PMID:12542526
• The Journal of investigative dermatology • 2010 • Genotypic and clinical spectrum of self-improving collodion ichthyosis: ALOX12B, ALOXE3, and TGM1 mutations in Scandinavian patients. PMID:19890349
• Medicine • 2025 • A case report and literature review of self-improving collodion baby in the newborn. PMID:40193669

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