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Prevalence data is limited. To date less than 35 cases have been reported in the literature worldwide.

Diagnosis is often made at birth, in newborns presenting with craniosysnostosis, cleft lip and/or palate and typical facial dysmorphism. Diagnosis could be made antenatally if the fetus presents omphalocele, facial cleft, caudal appendage or sacral anomalies. Children have psychomotor and growth delay. Intellectual disability forms part of the spectrum, and when present is typically moderate; however, patients are sometimes only limited by learning difficulties. Hearing loss is possible and should be monitored. Radioulnar synostosis, vesicorenal and genital anomalies can also occur.

3MC syndrome is due to biallelic point mutations or deletions in one of the 3 known causative genes COLEC10 (8q24.12), COLEC11 (2p25.3), and MASP1 (3q27.3). These genes code for factors involved in the activation of complement via the lectin or alternative pathways.

Diagnosis is suspected on clinical presentation (particularly by the association of craniosynostosis, intellectual disability and typical facial dysmorphism) and confirmed by genetic testing including targeted sequencing of the 3 genes COLEC10, COLEC11 and MASP1/3.

Differential diagnosis includes syndromic craniosynostoses, such as Crouzon disease.

Prenatal diagnosis is possible if a pathogenic variant has previously been identified in a family member.

Transmission is autosomal recessive. Genetic counseling should be offered to at-risk couples (both individuals are carriers of a disease-causing mutation) informing them of the 25% risk of having an affected child at each pregnancy. Consanguineous families are more prone to present this rare disorder.

Early surgical repair is provided for craniosynostosis, cleft lip/palate, caudal appendage.

Prognosis is linked to visceral malformations, growth restriction and intellectual disability.