Adams-Oliver syndrome induced by dedicator of cytokinesis 6 gene mutation: a case report and literature review / 中华神经科杂志

ABSTRACT

Objective To analyze the clinical manifestation and genetic testing in a patient with Adams-Oliver syndrome (AOS) and summarize clinical and genetic characteristics of the dedicator of cytokinesis (DOCK) 6 gene related AOS through reviewing related references.Methods Information of the proband who was hospitalized in Affiliated Children Hospital of Capital Institute of Pediatrics in October 2016 and her family members as well as their DNA samples were collected.The gene sequencing was performed using next generation sequencing technology.Using "Adams-Oliver syndrome"and "DOCK6" as key words,the relevant articles were searched from the Pubmed,China National Knowledge Internet and Wanfang databases and reports of 19 cases were reviewed.Results The proband is an eight months old girl.She presented with severe developmental delay,terminal transverse limb defects and visual loss after birth,and then suffered from tonic seizures and myoclonic seizures at two months old.By physical examination she was found to have esotropia and visual loss.The distal phalanx and nail of the right second-fourth fingers were absent,while the phalangette of the left second-fourth fingers and bilateral distal phalanges of toes were short with small nails attachment.Thyroid function test showed hypothyroidism.The ocular fundus examination showed the residual vitreous artery in the left eye and the retinal pigment degeneration in the right eye.CT scan showed multiple bilateral periventricular calcification and cranial magnetic resonance imaging showed bilateral periventricular lesion.Two heterozygous mutations were identified in DOCK6 geneone was a known pathogenic mutation (p.L1064Vfs*60),and the other was a novel splice site mutation (c.873+ 1G＞A).By analyzing this case and reported 19 cases,the common performances of DOCK6 gene related AOS included terminal transverse limb defects (20/20),aplasia cutis congenita (18/20),ocular abnormalities (13/20),seizures (12/20),mental retardation (12/20),microcephaly (10/20),cardiovascular malformations (10/20),intrauterine growth retardation (6/20).The mutation of the DOCK6 gene was found to be dominated by frameshift mutation and splice site mutation.Conclusions If either terminal transverse limb defects or aplasia cutis congenita was detected in a patient,AOS should be under consideration.In addition,autosomal recessive inheritance,nervous system and eyes involvement will further indicate DOCK6 gene related AOS.