Abstract
Cranioectodermal dysplasia (CED) or Sensenbrenner syndrome is a very rare autosomal-recessive disease that is characterized by craniofacial, skeletal and ectodermal abnormalities. The proteins encoded by six CED-associated genes are members of the intraflagelline transport (IFT) system, which serves an essential role in the assembly, maintenance and function of primary cilia. The current study identified compound novel heterozygous IFT122 (NM_052985.3) variants in a male Chinese infant with CED. The latter variant changes the length of the protein and may result in the partial loss-of-function of IFT122. With the simultaneous presence of frameshift and stop-loss variants, the patient manifested typical CED with fine and sparse hair, macrocephaly, dysmorphic facial features and upper limb phocomelia. A number of unusual phenotypic characteristics were additionally observed and included postaxial polydactyly of both hands and feet. The molecular confirmation of CED in this patient expands the CED-associated variant spectrum of IFT122 in CED, while the manifestation of CED in this patient provides additional clinical information regarding this syndrome. Moreover, the two variants identified in the proband provide a novel perspective into the phenotypes caused by different combinations of variants.