Monoallelic missense mutations in HIST1H4C in three individuals were associated with a syndrome of growth delay, microcephaly and intellectual disability. The patients also presented with characteristic facial features and foot ray anomalies.
A family presented with a distinct syndrome of global developmental delay and hypotonia. Whole genome genotyping and exome sequencing mapped the disease locus to the chromosome 21q22.11 and identified a homozygous missense variant in PAXBP1.
In a Chinese Han family, novel compound heterozygous mutations were identified in KARS. The patients segregated with a newly defined subtype of leukoencephalopathy associated with sensorineural hearing impairment.
Loss of function ROBO1 variants were identified in three families. Each proband had a ventricular septal defect, and one proband had tetralogy of Fallot. Additionally, a microdeletion in an individual with congenital heart disease was found in the medical literature. Mouse models showed perturbation of the Slit-Robo signalling pathway, causing septation and outflow tract defects and craniofacial anomalies. Two probands had variable facial features consistent with the mouse model.
The authors clinically ascertained a cohort of 124 individuals referred for frontonasal dysplasia. They identified six individuals with a similar phenotype, including one discordant monozygous twin. Facial features were remarkable by nasal deformity with creased ridge and depressed or absent tip, widely spaced eyes, almond-shaped palpebral fissures, and downturned corners of the mouth. All had apparently normal psychomotor development. In addition, upper limb anomalies, frontonasal encephalocele, corpus callosum agenesis, choanal atresia, and congenital heart defect were observed. The authors identified five reports in the literature of patients presenting with the same phenotype. Exome sequencing was performed on DNA extracted from blood of two individuals, no candidate gene was identified.
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