LAUSR

To the Editor: We report a Hispanic female with significant delay in intellectual and motor development, microcephaly, hypotonia, deafness, congenital heart defects including a patent ductus arteriosus and a bicuspid aortic valve, and craniofacial features overlapping with oculoauriculofrontonasal syndrome (OAFNS) including hypertelorism, mandibular hypoplasia, broad bifid nose, depressed nasal bridge, widely spaced maxillary central incisors, left microtia (Grade I), right microtia/atresia (Grade III), right ear skin tag, right iris coloboma, and macrostomia (Figure 1A-C). The proband was born to non-consanguineous healthy parents after uneventful pregnancy without complications including maternal diabetes, referred to us at age 3 years. She had long slender fingers and toes with normal fingernails and toenails. Brain MRI studies at 1 year of age showed hypogenesis of the splenium of the corpus callosum. Differential diagnoses included OAFNS based on her craniofacial dysmorphic features although severe intellectual disability was atypical for OAFNS. Single-nucleotide polymorphism (SNP) microarray study was normal. Whole exome sequencing was performed at age 10 years in comparison with her parents and a healthy younger brother. A novel de novo SMARCE1 missense alteration c.752G > A, p.Arg251Gln (ENST00000348513 NM_003079), was identified and confirmed by Sanger sequencing in the patient