Expanding the clinical phenotype of patients with a ZDHHC9 mutation

In 2007, 250 families with X-linked intellectual disability (XLID) were screened for mutations in genes on the X-chromosome, and in 4 of these families, mutations in the ZDHHC9 gene were identified. The ID was either isolated or associated with a marfanoid habitus. ZDHHC9 encodes a palmitoyl transferase that catalyzes the posttranslational modification of NRAS and HRAS. Since this first description, no additional patient with a ZDHHC9 mutation has been reported in the literature. Here, we describe a large family in which we identified a novel pathogenic ZDHHC9 nonsense mutation (p.Arg298*) by parallel sequencing of all X-chromosome exons. The mutation cosegregated with the clinical phenotype in this family. An 18-year-old patient and his 40-year-old maternal uncle were evaluated. Clinical examination showed normal growth parameters, lingual fasciculation, limited extension of the elbows and metacarpophalangeal joints, and acrocyanosis. There was neither facial dysmorphism nor marfanoid habitus. Brain MRI detected a dysplastic corpus callosum. Neuropsychological testing showed mild intellectual disability. They both displayed generalized anxiety disorder, and the younger patient also suffered from significant behavior impairment that required attention or treatment. Speech evaluation detected satisfactory spoken language since both were able to provide information and to understand conversations of everyday life. Occupational therapy examination showed impaired visual-spatial and visual-motor performance with poor drawing/graphic skills. These manifestations are not specific enough to guide ZDHHC9 screening in patients with ID, and emphasize the value of next generation sequencing for making a molecular diagnosis and genetic counseling in families with XLID

Influence of the sagittal balance of the spine on the anterior pelvic plane and on the acetabular orientation

The Anterior Pelvic Plane (APP), defined by the anterior superior iliac spines and the pubic tubercle, was commonly used as reference for positioning and postoperative evaluation of the orientation of the acetabular cup in total hip arthroplasty. APP was assumed to be vertical, but was not observed always so, mostly because of associated spinal diseases inducing perturbations in the harmony of the sagittal balance of the pelvi-spinal unit. Consequently a sagittal rotation of the pelvis occurs, and so a tilt of the APP which alters directly the orientation of the cup in upright position. An analysis of the APP tilt related to the sagittal balance of the spine was provided and its implication on the cup orientation. It appeared essential for an individual adjustment of the cup positioning to avoid a functional mal-position which can lead to an increased risk of dislocation and impingement