Keywords:
Genetic defects, Congenital, Medico-legal issues, Conventional radiography, Paediatric, Extremities, Bones
Authors:
L. H. L. De Beuckeleer, K. Carpentier, M. Pouillon; Antwerp/BE
DOI:
10.1594/essr2014/P-0042
Results
On MR imaging of the brain,
a large skull defect is seen at the right posterolateral aspect on sagittal T1-WI (Figs.
1 & 2),
together with a hypoplastic corpus callosum.
On axial FLAIR and T2-weighted images, a bilateral 'closed lip' schizencephaly (Figs.
3 & 4) is noted.
The sagittal T1-weighted images show periventricular nodules (Fig.
1),
corresponding to calcifications as shown on a non-enhanced CT scan of the head,
performed afterwards (Fig.5).
Plain radiographs of the hands and forearms show a normal aspect of the right metacarpal bones,
but only one single ossification center in the first finger,
corresponding to the proximal phalangeal bone.
The right hand has a "lobster-like"appearance and fingers are rudimentary,
corresponding to a so-called brachydactyly type E (Fig.6).
At the left side,
the metacarpals are normal and the proximal phalangeal bones show normal ossification centers (Fig.7).
The radius and ulna are normal at both sides.
Sequential DNA analysis shows a homozygous c.2520dupT (p.Arg841Serfs*6) in exon 21 of the DOCK6 gene,
thereby confirming the clinically presumed diagnosis of AOS2.
This gene encodes a member of the dedicator of cytokinesis (DOCK) family of atypical guanine nucleotide exchange factors,
which interact with small GTPase enzymes and are components of intracellular signaling networks.
The encoded protein is a group C DOCK protein and plays a role in actin cytoskeletal reorganization by activating the Rho GTPases Cdc42 and Rac1.
Mutations in this gene are associated with Adams-Oliver syndrome 2.
[4,5].
Both parents turned out to be heterozygous carrier of the abovementioned mutation in the DOCK6 gene.
The inheritance of the gene defect happened in an autosomal recessive pattern.