TY - JOUR
T1 - Significant overlap and possible identity of macrocephaly capillary malformation and megalencephaly polymicrogyria-polydactyly hydrocephalus syndromes
AU - Gripp, Karen W.
AU - Hopkins, Elizabeth
AU - Vinkler, Chana
AU - Lev, Dorit
AU - Malinger, Gustavo
AU - Lerman-Sagie, Tally
AU - Dobyns, William B.
PY - 2009/5
Y1 - 2009/5
N2 - We report on three patients with macrocephaly and polymicro- gyria, and additional anomalies seen in megalencephaly polymicrogyria-polydactyly hydrocephalus (MPPH) and macrocephaly capillary malformation (MCM) syndromes. Based on their characteristic brain malformations they were originally diagnosed with MPPH. In one patient the phenotype evolved during early infancy, and ultimately resulted in a diagnosis of MCM. A second was prenatally diagnosed with MPPH, but postnatally visualized capillarymalformations led to a diagnosis of MCM. In a third, the original MPPH diagnosis was reconsidered after a critical review revealed additional subtle findings suggestive of MCM. Characteristic brain malformations are thought to distinguish between MPPH with perisylvian polymicrogyria, and MCM with megalencephaly with Chiari 1 malformation. However, polymicrogyria was reported in a significant number of patients with MCM. Conversely, upon review of imaging studies of patients with MPPH, we noted progressive crowding of the posterior fossa and acquired tonsil- lar herniation, a process deemed characteristic for MCM. Thus, neither polymicrogyria nor acquired tonsillar herniation are distinguishing features, and occur in both disorders. In addition to brain abnormalities, shared findings include cognitive impairment, coarse facial features and postaxial polydactyly. Facial nevus flammeus and cutis marmorata are most noticeable in infancy, and ligamentous laxity and redundant soft tissue are somewhat subjective findings. While asymmetric overgrowth is considered typical for MCM, it is not universally present. These variable and subtle findings can be identified in patients with MPPH. We propose that MPPH and MCM may not represent distinct entities and that the term MPPH-CM syndrome be used to describe this spectrum.
AB - We report on three patients with macrocephaly and polymicro- gyria, and additional anomalies seen in megalencephaly polymicrogyria-polydactyly hydrocephalus (MPPH) and macrocephaly capillary malformation (MCM) syndromes. Based on their characteristic brain malformations they were originally diagnosed with MPPH. In one patient the phenotype evolved during early infancy, and ultimately resulted in a diagnosis of MCM. A second was prenatally diagnosed with MPPH, but postnatally visualized capillarymalformations led to a diagnosis of MCM. In a third, the original MPPH diagnosis was reconsidered after a critical review revealed additional subtle findings suggestive of MCM. Characteristic brain malformations are thought to distinguish between MPPH with perisylvian polymicrogyria, and MCM with megalencephaly with Chiari 1 malformation. However, polymicrogyria was reported in a significant number of patients with MCM. Conversely, upon review of imaging studies of patients with MPPH, we noted progressive crowding of the posterior fossa and acquired tonsil- lar herniation, a process deemed characteristic for MCM. Thus, neither polymicrogyria nor acquired tonsillar herniation are distinguishing features, and occur in both disorders. In addition to brain abnormalities, shared findings include cognitive impairment, coarse facial features and postaxial polydactyly. Facial nevus flammeus and cutis marmorata are most noticeable in infancy, and ligamentous laxity and redundant soft tissue are somewhat subjective findings. While asymmetric overgrowth is considered typical for MCM, it is not universally present. These variable and subtle findings can be identified in patients with MPPH. We propose that MPPH and MCM may not represent distinct entities and that the term MPPH-CM syndrome be used to describe this spectrum.
KW - Congenital heart disease
KW - Hemangiomata
KW - Syndactyly
UR - http://www.scopus.com/inward/record.url?scp=66849115642&partnerID=8YFLogxK
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U2 - 10.1002/ajmg.a.32732
DO - 10.1002/ajmg.a.32732
M3 - Article
C2 - 19353582
AN - SCOPUS:66849115642
SN - 1552-4825
VL - 149
SP - 868
EP - 876
JO - American Journal of Medical Genetics, Part A
JF - American Journal of Medical Genetics, Part A
IS - 5
ER -