Titel: A rare case of 3MC syndrome with thoracic aortic dissection
ID: P-ClinG-058
Art: Postertalk
Redezeit: 2 min
Session: Poster Session
ClinG 2

Referent: Maria Grossmann (Dresden/DE)

Abstract - Text


The term '3MC syndrome' is derived from the Mingarelli, Malpuech, Michels and Carnevale syndromes. The main features of 3MC syndrome are facial dysmorphisms (hypertelorism, blepharophimosis, blepharoptosis, highly arched eyebrows). Beside these symptoms cleft lip and palate, postnatal growth deficiency, cognitive impairment, hearing loss, craniosynostosis, radioulnar synostosis, genital and vesicorenal anomalies can occur. Rarely described are anterior chamber defects, cardiac anomalies, caudal appendage, umbilical hernia, and diastasis recti. The 3MC syndrome is inherited in an autosomal recessive manner. Causative mutations are described in MASP1, COLEC10 and COLEC11 genes. Only a few patients with 3MC syndrome were described to date.

Here we describe a 44-year-old patient of Egyptian origin referred because of Stanford type A thoracic aortic dissection, spontaneous deep vein thrombosis, and multiple small intracerebral haemorrhage. He also presented with blepharophimosis, blepharoptosis, epicanthus inversus, high-arched eyebrows, skull asymmetry/craniosynostosis, high palate, and obesity. Furthermore, he had hearing loss, thought to be the result of a boxing accident at 15 years of age. According to patient's statement, his parents are not consanguineous. Photos of his parents did not show the mentioned above patient's features of cranium and face.

Chromosome and microarray analyses showed no anomalies. No clearcut pathogenic mutation for the thoracic aortic dissection was detected. In contrast, NGS analysis revealed a homozygous nonsense mutation c.1612C>T, p.(Arg538*) in the last codon of MASP1 gene within the serine protease domain of the protein isoform MASP-3. The variant is neither described in HGMD Professional 2021.3, nor in ClinVar and LOVD database. It is designated as rs369868022 in NCBI dbSNP and detected twice in heterozygous and not in homozygous state under 125650 (control) individuals (allele frequency 0,0008%) of gnomAD v2.1.1 database. According to the 5-tiered ACMG classification system for sequence variants, we classify the detected sequence variant as likely pathogenic (class 4). MASP1 gene encodes three alternative splice products (MASP-1, MASP-3, and MAp44) playing roles in the lectin complement pathway and possibly involved in coagulation.

In summary, we hypothesize that the aortic dissection as well as the coagulation disorders could be part of 3MC syndrome. Novel MASP1 mutations and phenotypic features could expand the genotypic and phenotypic spectrum of the 3MC syndrome.