MASP1‐related 3MC syndrome in a patient from Turkey

Abstract

3MC syndrome is a rare condition manifesting with typical facial appearance, postnatal growth deficiency, skeletal manifestations, and genitourinary tract anomalies. 3MC is caused by biallelic pathogenic variants in MASP1, COLEC11, or COLEC10. Here, we report an affected subject of Kurdish origin from Turkey presenting with facial dysmorphisms, such as, hypertelorism, blepharophimosis, blepharoptosis, highly arched eyebrows, umbilical hernia, and caudal appendage. These features were compatible with 3MC syndrome. Molecular analysis revealed a novel homozygous pathogenic variant, c.310C > T; p.Gln104Ter in the MASP1 gene, resulting in a premature stop codon. Few subjects with 3MC syndrome have been reported in the literature so far. Thus, detailed study of this subject contributes to the evolving clinical and genetic characterization of 3MC syndrome.

‘A child with Malpuech–Michels–Mingarelli–Carnevale syndrome and ADHD and major depressive disorder’

“…To the best of our knowledge, there has not been a case of 3MC syndromes comorbid with ODD or MDD in the previous literature. In other cases, no accompanying psychiatric disorder was found or reported (Atik et al , 2015; Urquhart et al , 2016; Gardner et al , 2017; Munye et al , 2017; Basdemirci et al ., 2019; Durmaz and Altiner, 2021).…”

“…Homozygous mutations in the MASP1, COLEC10 , or COLEC11 genes are found in the etiology of 3MC syndrome (Rooryck et al ., 2011; Munye et al ., 2017). MASP1, COLEC10 , or COLEC11 encode proteins involved in the lectin complement pathway, and pathogenic variants lead to 3MC syndrome (Rooryck et al ., 2011; Munye et al ., 2017); however, the effects of these genes on the pathogenesis of 3MC syndrome are not entirely clear (Durmaz and Altiner, 2021). Zebrafish embryos with MASP1 or COLEC11 mutations have been found to have craniofacial abnormalities and pigment deficiencies, indicating migration defects (Rooryck et al ., 2011).…”

“…Although these 4 syndromes have many distinct characteristics, they are collectively called ‘3MC syndrome’ due to their multiple craniofacial similarities (Titomanlio et al ., 2005). 3MC syndrome can be accompanied by facial dysmorphism such as high arched eyebrows (70–95% of cases), cleft lip and palate (40–68% of cases), blepharophimosis, blepharoptosis, downward-sloping palpebral fissures, hypertelorism, hearing loss (65% of cases) growth retardation (in 60% of cases), mental retardation (in 60% of cases), elongated coccyx, caudal appendage (37% of cases), vesicorenal anomalies (20–30% of cases), cardiac defect (about 20% of cases), genital anomalies, radioulnar synostosis and skeletal conditions such as craniosynostosis (Rooryck et al ., 2011; Durmaz and Altiner, 2021). Although the exact prevalence of 3MC syndrome is unknown, it is documented to be a very rare syndrome (Durmaz and Altiner, 2021).…”

“…The MASP1, COLEC10 , or COLEC11 genes are involved in the migration of neural crest cells during the embryonic period (Rooryck et al ., 2011; Munye et al ., 2017). To the best of our knowledge, a total of 49 genetically confirmed 3MC syndrome cases from 35 families have been reported so far (Priolo et al ., 2007; Atik et al ., 2015; Urquhart et al ., 2016; Gardner et al ., 2017; Munye et al ., 2017; Basdemirci et al ., 2019; Durmaz and Altiner, 2021). Although 3MC syndrome is rare, it is important in terms of accompanying symptoms affecting multiple systems and its comorbidity with psychiatric disorders.…”

3MC syndrome: molecular findings in previously reported and milder patients expand the natural history and phenotypic spectrum

“…The exact incidence and prevalence of 3MC syndrome are unknown, though it is considered to be rare. To date only 58 cases have been reported in the literature; 27 cases with MASP1 variants, 17 cases with COLEC11 variants and 14 cases with COLEC10 variants (Basdemirci et al, 2019;Çakmaklh and Kandur, 2019;Gajek et al, 2020;Lawson et al, 2020;Agaoglu and Akgun Dogan, 2021;Durmaz and Altıner, 2021;Mohammadi et al, 2021;Rabin et al, 2022).…”