A de novo 1.1 Mb microdeletion of chromosome 19p13.11 provides indirect evidence for EPS15L1 to be a strong candidate for split hand split foot malformation

Abstract

We describe a 3.5 year old girl presenting with short stature, developmental delay, marked muscular hypotonia with ataxia, premature pubarche, and dysmorphic features. A 1.07–1.12 Mb-sized de novo microdeletion of chromosome 19p13.11 is most likely the cause for the clinical phenotype. The patient did not show any abnormalities of the extremities which contrasts with the finding of one previously reported patient with an overlapping deletion presenting with split hand and foot malformation (SHFM). The remarkable difference is that in the previously described patient but not in the patient reported herein the genes EPS15L1 and CALR3 were deleted. As EPS15L1 has been associated with limb development previously, the presented case provides indirect evidence that this may be a new candidate gene for SHFM. A possible genotype–phenotype correlation is provided based on literature review and comparison of our patient to the previously reported patients with overlapping or partly overlapping copy number variations in 19p13.11.