SHANK2 Mutations Result in Dysregulation of the ERK1/2 Pathway in Human Induced Pluripotent Stem Cells-Derived Neurons and Shank2(−/−) Mice

SHANK2 (ProSAP1) is a postsynaptic scaffolding protein of excitatory synapses in the central nervous system and implicated in the development of autism spectrum disorders (ASD). Patients with mutations in SHANK2 show autism-like behaviors, developmental delay, and intellectual disability. We generated human induced pluripotent stem cells (hiPSC) from a patient carrying a heterozygous deletion of SHANK2 and from the unaffected parents. In patient hiPSCs and derived neurons SHANK2 mRNA and protein expression was reduced. During neuronal maturation, a reduction in growth cone size and a transient increase in neuronal soma size were observed. Neuronal proliferation was increased, and apoptosis was decreased in young and mature neurons. Additionally, mature patient hiPSC-derived neurons showed dysregulated excitatory signaling and a decrease of a broad range of signaling molecules of the ERK-MAP kinase pathway. These findings could be confirmed in brain samples from Shank2(−/−) mice, which also showed decreased mGluR5 and phospho-ERK1/2 expression. Our study broadens the current knowledge of SHANK2-related ASD. We highlight the importance of excitatory-inhibitory balance and mGluR5 dysregulation with disturbed downstream ERK1/2 signaling in ASD, which provides possible future therapeutic strategies for SHANK2-related ASD.

Bilateral anterior superior iliac spine apophysis avulsion fractures in a skeletally mature patient: case report and literature review

We present a case of bilateral anterior superior iliac spine avulsion fractures in an adult patient who was involved in a road traffic collision. Her injuries were managed conservatively and she has had an uncomplicated recovery with a good outcome. This is, to our knowledge, the only reported case of bilateral simultaneous anterior superior iliac spine apophyseal avulsion fractures in an adult.

Surgical Reconstruction Methods following Radical Excision of Distal Ulna Osteosarcoma in Both Skeletally Mature and Immature Patients

The distal ulna has always been considered to be expendable and its removal has been advocated for a variety of post-traumatic degenerative and oncological conditions but recent studies showed that the distal radioulnar joint allows supination and protonation of the forearm and is important to one’s grip strength and lifting ability. Several prosthesis models have already been made to replace the mechanical functionality of the distal radioulnar joint. We present two cases of females aged 22 and 12 years, respectively, who presented with wrist pain and swelling without any history of trauma and with terminal degree limitation in wrist movements due to tenderness and swelling. Both of them did not have any distant metastasis upon radiographic staging. The skeletally mature patient underwent radical excision of the distal ulnar osteosarcoma and received a distal radioulnar joint replacement prosthesis (Scheker prosthesis). The other skeletally immature patient underwent radical excision of the involved distal ulnar osteosarcoma with stabilization of the residual ulnar stump using the extensor carpi ulnaris sling in a modified version of the Goldner and Hayes technique. Both of our patients were treated according to the protocols of our multidisciplinary clinic sarcoma team by starting with neoadjuvant chemotherapy, followed by surgery and adjuvant chemotherapy. Both registered an almost complete restoration of the normal wrist and hand function and were in complete remission for 26 and 24 months, respectively. Based on our literature review, these are some of the extremely rare cases in which the osteosarcoma affected an unusual site (the distal ulna where they underwent a rare type of reconstruction status following radical excision of a malignant tumor).

Asymptomatic Dysplasia Epiphysealis Hemimelica of the Shoulder in a Skeletally Mature Patient with Normal Function

Dysplasia epiphysealis hemimelica is a rare osteocartilaginous overgrowth syndrome of bone epiphysis, mostly encountered in the lower limbs of immature skeleton patients. We report a case of proximal humerus presentation in an adult male, with neither articular involvement nor clinical dysfunction. This case highlights the importance of stratification into intra- and extra-articular lesions, as this distinction ultimately influences both symptoms and treatment outcome. In addition, the case highlights the importance of specific imaging modalities, such as CT and MR images, which provide excellent anatomic location of the lesion, adequate extension of cartilaginous components, exact status of articular cartilage, and accurate assessment of neighboring structures, such as vessels, nerves, ligaments, tendons, and muscles. The imaging features are described, the relevant literature is reviewed, and salient features are discussed.