The “megalencephaly-capillary malformation” (MCAP) syndrome: The nomenclature of a highly recognizable multiple congenital anomaly syndrome

Authors


  • Editor's Note
  • The preceding Letter by Collins and the ensuing Response by Mirzaa and Dobyns raise the long-standing, never-ending issue regarding the naming of genetic syndromes. Collins (and her parent associates) objects to the recent proposal by Mirzaa et al. [2012] to rename the macrocephaly-capillary malformation syndrome because this change is potentially confusing to families, their care providers, and anyone searching for information on the condition. As Collins points out, this represents the third name change for this entity. Mirzaa et al. proposed using the designation MCAP because megalencephaly (not simply macrocephaly) is a “striking” feature of the condition. This suggestion is compelling because megalencephaly is a more accurate description of this manifestation that occurs consistently in the syndrome.
  • The naming of genetic syndromes is clearly an age old challenge. Simply peruse most syndrome entries in OMIM to witness the various names for many conditions. The naming of a syndrome by its component features has many limitations (as pointed out in the Letter), most importantly, that one or two of the features rarely captures the essence or clinical spectrum of the entity, oversimplifies designation, and overemphasizes selected manifestations.
  • However, at the time of original observation and description of a condition, indicating by selected component manifestations is the simplest option. (The use of eponyms in this setting is another important topic but for a future dialogue.) This discourse underscores the need for an international committee that makes consensus recommendations regarding the naming of a syndrome.
    • John C. Carey

    • Editor-in-Chief

Correspondence to:

Ghayda M. Mirzaa and William B. Dobyns, Seattle Children's Research Institute, Ctr for Integrative Brain Research, 1900 Ninth Avenue, Mailstop C9S-10, Seattle, WA 98101.

E-mail: gmirzaa@u.washington.edu, wbd@uw.edu

To the Editor

We acknowledge and appreciate the concerns raised by Ms. Collins in the above letter to the Journal. Indeed, this unique syndrome been renamed several times, primarily as understanding of its' distinguishing features evolved. Originally termed the macrocephaly-cutis marmorata telangiectatica congenita (M-CMTC) syndrome [Moore et al., 1997], the name was later shortened to “macrocephaly-cutis marmorata” (M-CM) syndrome as the former name was considered “unwieldy” [Cohen, 2003]. Soon after, experts in dermatology, dysmorphology, and vascular surgery recognized that both terms are misnomers for the characteristic cutaneous vascular anomalies, which are predominantly simple capillary malformations, and proposed the term “macrocephaly-capillary malformation” syndrome [Toriello and Mulliken, 2007]. In our recent study of this syndrome, we sought to further correct the remaining inaccuracy in its' name [Mirzaa et al., 2012]. Arguably the most striking feature of this syndrome is brain overgrowth or megalencephaly, which is most often congenital and appears to be universally progressive, despite neurosurgical intervention for associated ventriculomegaly or hydrocephalus [Conway et al., 2007; Mirzaa et al., 2012]. True megalencephaly is a specific feature seen in a small group of syndromes, much smaller than the heterogeneous group of disorders with large head size overall.

We plan to continue to use the term “megalencephaly-capillary malformation” syndrome (MCAP) in our ongoing studies for several very clear reasons. First, we propose that “megalencephaly” is the correct medical and biological term. It implies a specific increased risk for accompanying medical problems such as hydrocephalus, Chiari malformation type 1 (and less severe cerebellar tonsilar ectopia), and the cortical malformation polymicrogyria. These risks are not characteristic of most forms of simple large head size or macrocephaly. Second, this minor change brings megalencephaly-capillary malformation syndrome into line with other syndromes with brain overgrowth, all of which have or will have the term “megalencephaly” in the name. Third, while we readily acknowledge a long history of diagnostic difficulties, the underlying gene (PIK3CA) has proven to be a central player in a very important biological pathway in the cell [Rivière et al., 2012]. Furthermore, the literature suggests that MCAP (or M-CM) is not rare. We have now identified more than 100 children with this syndrome, which, in our opinion, is rapidly becoming one of the very well known syndromes in the field; so diagnostic confusion should hopefully no longer be a problem.

Indeed, our new understanding of the spectrum of features and the molecular basis of this syndrome and overlapping disorders will undoubtedly lead to improved diagnosis and hopefully specific treatments.

We thank Ms. Collins and the journal for the opportunity to better explain our reasons for the minor name change.

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