Craniotubular Dysplasia Ikegawa Type: Further Delineation of the Phenotype

Craniotubular Dysplasia Ikegawa type is a sclerosing bone disorder recently identified in five patients from four independent Indian families. It is caused by homozygous or compound heterozygous mutations in TMEM53. Deficient TMEM53 leads to overactive BMP signaling which promotes bone formation. Here, we present another three siblings with intronic mutations in TMEM53, identified by exome sequencing, from a Caucasian family. All three siblings displayed skeletal and radiographic features, similar to the earlier described individuals. All our patients had additional features such as cardiac and urogenital anomalies. Our results confirm the phenotype of CTDI. We discuss whether the additional features in our patients are separate from CTDI or reflect a broader spectrum of the syndrome.