Recognizable facial features in patients with alternating hemiplegia of childhood.
Alternating hemiplegia of childhood is an early onset neurodevelopmental disorder characterized by paroxystic episodes of alternating hemiplegia, variable degrees of intellectual disability, and dystonic movements. The main causative gene, ATP1A3, is also responsible for other neurodevelopmental disorders. While the neurological profile of this condition is well defined, the question whether a recognizable pattern of physical anomalies does exist in this condition is still open. We performed a morphological evaluation of 30 patients at different ages. All patients were evaluated independently by each author and evaluation sheets were compared, discussed, and agreed afterwards. This study started before the identification of ATP1A3 as the causative gene, and the patients were selected upon their neurological picture. Four of these 30 patients tested negative for ATP1A3 mutations and were excluded from the present work. On physical ground, almost all patients shared a similar physical phenotype consisting of hypotonia, long face, thin eyebrows, strabismus, hypertelorism, long palpebral fissures, downturned mouth, and slender habitus. Such phenotype is sufficiently typical to generate a recognizable gestalt. We also evaluated patients photographs taken from the parents in early childhood (6-20 months) to delineate a clinical profile possibly recognizable before the neurological signs suggest the diagnosis. Our data suggest that the typical early gestalt is sufficient to advise the molecular analysis of ATP1A3, even in absence of the pathognomonic neurological signs. Finally, since a number of patients is now adult, some information can be drawn on the phenotypic evolution of the facial appearance of patients with alternating hemiplegia of childhood. © 2016 Wiley Periodicals, Inc.
Istituto di Medicina Genomica, Università Cattolica del S. Cuore Roma, Roma, Lazio, Italy. fiorella.gurrieri@unicatt.it.
Fiorella
F
Gurrieri
Istituto di Medicina Genomica, Università Cattolica del S. Cuore Roma, Roma, Lazio, Italy.
Francesco Danilo
FD
Tiziano
Istituto di Clinica Pediatrica, Università Cattolica del S. Cuore Roma, Roma, Lazio, Italy.
Giuseppe
G
Zampino
Istituto di Medicina Genomica, Università Cattolica del S. Cuore Roma, Roma, Lazio, Italy.
Giovanni
G
Neri
D019943:Amino Acid Substitution; D002675:Child, Preschool; D003062:Codon; D019066:Facies; D005260:Female; D006429:Hemiplegia / Q000175:diagnosis* / Q000235:genetics; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D009154:Mutation; D010641:Phenotype; D011296:Prenatal Diagnosis; D000254:Sodium-Potassium-Exchanging ATPase / Q000235:genetics
C488756:ATP1A3 protein, human; D003062:Codon; D000254:Sodium-Potassium-Exchanging ATPase
alternating hemiplegia of childhood; phenotype