Michels syndrome, Carnevale syndrome, OSA syndrome, and Malpuech syndrome: Variable expression of a single disorder (3MC syndrome)?

Abstract

We report on a 3‐year‐old girl with Michels syndrome, a rare condition characterized by craniosynostosis, blepharophimosis, ptosis, epicanthus inversus, cleft lip/palate, abnormal supra‐umbilical abdominal wall, and mental deficiency. The phenotypic findings are compared with the six previously reported Michels cases, and with patients referred to as Carnevale, OSA, and Malpuech syndromes. Michels syndrome is characterized by cleft lip and palate, anterior chamber anomalies, blepharophimosis, epicanthus inversus, and craniosynostosis. Carnevale syndrome shows hypertelorism, downslanting palpebral fissures, ptosis, strabismus synophrys, large and fleshy ears, and lozenge‐shaped diastasis around the umbilicus. OSA syndrome resembles Carnevale, with humeroradial synostoses, and spinal anomalies as extra features. Malpuech syndrome shows IUGR, hypertelorism, cleft lip and palate, micropenis, hypospadias, renal anomalies, and caudal appendage. All are autosomal recessive. Despite the presence of apparently distinctive key features, it appears that these four entities share multiple similarities in the facial Gestalt and the pattern of MCA. Those similarities lead us to postulate that they belong to the same spectrum, which could be referred to as “3MC syndrome” (Malpuech‐Michels‐Mingarelli‐Carnevale syndrome). © 2005 Wiley‐Liss, Inc.

Asymmetrical skull, ptosis, hypertelorism, high nasal bridge, clefting, umbilical anomalies, and skeletal anomalies in sibs: Is Carnevale syndrome a separate entity?

“…We are not convinced that case 2 and 3 of the Kerstjens-Frederikse et al [2005] report have Malpuech syndrome, but we lack sufficient data to be sure about the latter and therefore followed the authors and included the patients. Six patients have been reported with Michels syndrome [Michels et al, 1978;Cunniff and Jones, 1990;De La Paz et al, 1991;Titomanlio et al, 2005]. We have kept the patient reported by Guion-Almeida and Rodini [1995] separately however, as in our opinion this patient resembles the patients reported by Carnevale et al [1989] and Mingarelli et al [1996] much more than those reported as having Michels syndrome.…”

“…These syndromes include Malpuech syndrome, Michels syndrome, Carnevale syndrome, OSA syndrome, and Mingarelli syndrome, and some include Juberg-Hayward syndrome as well. Titomanlio et al [2005] have suggested that the entities are in fact part of the same entity, and have proposed to name this 3MC The proband, a 4.5 year-old boy, was referred because of a progressive torticollis. He was the second-born child of healthy, consanguineous (first cousins) parents.…”

Mannan-Binding Lectin-Associated Serine Protease (MASP)-1 Is Crucial for Lectin Pathway Activation in Human Serum, whereas neither MASP-1 nor MASP-3 Is Required for Alternative Pathway Function

“…Genetic studies recently revealed that mutations in MASP1 and COLEC11 underlie the etiology of 3MC syndrome (16), a rare autosomal recessive disorder characterized by facial dysmorphism, short stature, intellectual disability, midline defects, and caudal appendage (17,18). The common denominator of causative MASP1 gene defects is the absence of a functional form of MASP-3, but in one individual a nonsense mutation was localized to the part of MASP1 encoding the common domains of MASP-1, MASP-3, and MAp44, most likely conferring a complete deficiency of these proteins in the homozygous state ( Fig.…”

The nosology of Richieri‐Costa/Guion‐Almeida syndrome(s)

“…However, partial overlap is evident with Michels, Carnevale, Malpuech, and OSA syndromes [Michels et al, 1978;Malpuech et al, 1983;Carnevale et al, 1989;Mingarelli et al, 1996], which are now considered a single entity [Titomanlio et al, 2005]; however, not all authors agree with this hypothesis [Al Kaissi et al, 2007]. These conditions all comprise specific eyelid anomalies (i.e., blepharoptosis, blepharophimosis, and epicanthus inversus) with hypertelorism.…”