title: Novel findings of left ventricular non-compaction cardiomyopathy, microform cleft lip and poor vision in patient with SMC1A-associated Cornelia de Lange syndrome.
abstract: Relatively few patients with Cornelia de Lange syndrome (CdLS) due to SMC1A mutation have been reported, limiting understanding of the full extent of the phenotype. Compared to children with classic NIPBL-associated CdLS, patients with SMC1A-associated CdLS have a milder physical phenotype with prominent intellectual disability, high rate of cleft palate and absence of limb reductions. We present a patient with SMC1A-associated CdLS who had typical features including developmental delay, seizure disorder, feeding difficulties, hirsutism, and cleft palate. She also was found to have three novel features: (i) left ventricular non-compaction (LVNC) cardiomyopathy; (ii) microform cleft lip; and (iii) severe hyperopia and astigmatism. These features have implications regarding potential insight into the pathogenesis of the disorder, screening, and medical management. Hypertrophic cardiomyopathy has previously been reported in SMC1A-associated CdLS, but to our knowledge this is the first reported child with LVNC. Previous reports have included children with isolated clefts of the palate without involvement of the lip. When cleft palate alone is associated with a disorder, the underlying pathophysiology for clefting is sometimes secondary due to mechanical blocking of the fusion of the palatal shelves with the developing tongue. The presence of microform cleft lip in this patient suggests that the pathophysiology of clefting in SMC1A is primary rather than secondary. Few studies report ophthalmologic findings specific to SMC1A. Based on these findings, LVNC cardiomyopathy and cleft lip should be considered features of SMC1A-associated CdLS. All patients should receive echocardiogram and undergo thorough ophthalmologic evaluation as part of routine CdLS care. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Division of Craniofacial Medicine, Seattle Children's Hospital, Seattle, Washington.
authors.forename: Tara L
authors.initials: TL
authors.lastname: Wenger
authors.affiliation: Division of Genetics, Seattle Children's Hospital, Seattle, Washington.
authors.forename: Penny
authors.initials: P
authors.lastname: Chow
authors.affiliation: Division of Neurology, Seattle Children's Hospital, Seattle, Washington.
authors.forename: Stephanie C
authors.initials: SC
authors.lastname: Randle
authors.affiliation: Division of Craniofacial Medicine, Seattle Children's Hospital, Seattle, Washington.
authors.forename: Anna
authors.initials: A
authors.lastname: Rosen
authors.affiliation: Division of Craniofacial Medicine, Seattle Children's Hospital, Seattle, Washington.
authors.forename: Craig
authors.initials: C
authors.lastname: Birgfeld
authors.affiliation: Division of Neurology, Seattle Children's Hospital, Seattle, Washington.|Division of Pulmonary and Sleep Medicine, Seattle Children's Hospital, Seattle, Washington.
authors.forename: Joanna
authors.initials: J
authors.lastname: Wrede
authors.affiliation: Division of Pediatric General and Thoracic Surgery, Seattle Children's Hospital, Seattle, Washington.
authors.forename: Patrick
authors.initials: P
authors.lastname: Javid
authors.affiliation: Division of Craniofacial Medicine, Seattle Children's Hospital, Seattle, Washington.|Division of Neurodevelopmental Disabilities, Seattle Children's Hospital, Seattle, Washington.
authors.forename: Darcy
authors.initials: D
authors.lastname: King
authors.affiliation: Division of Ophthalmology, Seattle Children's Hospital, Seattle, Washington.
authors.forename: Vivian
authors.initials: V
authors.lastname: Manh
authors.affiliation: Division of Craniofacial Medicine, Seattle Children's Hospital, Seattle, Washington.
authors.forename: Anne V
authors.initials: AV
authors.lastname: Hing
authors.affiliation: Division of Cardiology, Seattle Children's Hospital, Seattle, Washington.
authors.forename: Erin
authors.initials: E
authors.lastname: Albers
mesh_terms: D018797:Cell Cycle Proteins / Q000235:genetics*; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics*; D002971:Cleft Lip / Q000175:diagnosis / Q000235:genetics*; D003635:De Lange Syndrome / Q000175:diagnosis* / Q000235:genetics*; D004452:Echocardiography; D019066:Facies; D005260:Female; D056726:Genetic Association Studies; D006330:Heart Defects, Congenital / Q000175:diagnosis / Q000235:genetics*; D006801:Humans; D007223:Infant; D010641:Phenotype; D014786:Vision Disorders / Q000175:diagnosis / Q000235:genetics*; D000098550:Structural Maintenance of Chromosome Protein 1
chemical_list: D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; D000098550:Structural Maintenance of Chromosome Protein 1
keywords: Cornelia de Lange syndrome; astigmatism; cleft palate; hyperopia; hypertrophic cardiomyopathy; microform cleft lip; non-compaction cardiomyopathy; seizures