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.