Early activating somatic PIK3CA mutations promote ectopic muscle development and upper limb overgrowth.

PIK3CA-related overgrowth spectrum is a group of rare genetic disorders with asymmetric overgrowth caused by somatic mosaic PIK3CA mutations. Here, we report clinical data and molecular findings from two patients with congenital muscular upper limb overgrowth and aberrant anatomy. During debulking surgery, numerous ectopic muscles were found in the upper limbs of the patients. DNA sequencing, followed by digital polymerase chain reaction, was performed on DNA extracted from biopsies from hypertrophic ectopic muscles and identified the somatic mosaic PIK3CA hotspot mutations c.3140A > G, p.(His1047Arg) and c.1624G > A, p.(Glu542Lys) in a male (patient 1) and a female (patient 2) patient, respectively. Patient 1 had four ectopic muscles and unilateral isolated muscular overgrowth while patient 2 had 13 ectopic muscles and bilateral isolated muscular overgrowth of both upper limbs, indicating that her mutation occurred at early pre-somitic mesoderm state. The finding of PIK3CA mutations in ectopic muscles highlights the importance of PIK3CA in cell fate in early human embryonic development. Moreover, our findings provide evidence that the disease phenotype depends on the timing of PIK3CA mutagenesis during embryogenesis and confirm the diagnostic entity PIK3CA-related muscular overgrowth with ectopic accessory muscles.

Chlorido(1,2-dimethyl-1H-imidazole-κN){2-[(diphen-oxy-phosphan-yl)-oxy]phenyl-κC,P}palladium(II).

The Pd atom in the title compound, [Pd(C(18)H(14)O(3)P)Cl(C(5)H(8)N(2))], adopts a slightly distorted square-planar coordination geometry, with the metallated carbon positioned trans to the Cl atom. The crystal structure is stabilized by several weak C-H⋯O and C-H⋯Cl hydrogen-bond inter-actions. One of the phenyl rings is disordered over two almost equally occupied sites.

cis-Dichloridobis[tris-(2-methyl-phen-oxy)phosphane-κP]palladium(II).

In the title compound, [PdCl(2)(C(21)H(21)O(3)P)(2)], the Pd atom adopts a slightly distorted square-planar coordination geometry, with pairs of the equivalent ligands in cis positions. Adjacent mol-ecules are linked by weak C-H⋯Cl hydrogen bonds. The crystal structure is additionally stabilized by π-π stacking inter-actions between the aromatic rings [shortest centroid-centroid distance = 3.758 (4) Å].

Upper-extremity Spasticity-reducing Treatment in Adjunct to Movement Training and Orthoses in Children with Cerebral Palsy at Gross Motor Function- and Manual Ability Classification System Levels IV-V: A Descriptive Study.

Covering a 20-year period of work with children with severe cerebral palsy (CP) within a Swedish habilitation service, changes in passive wrist extension with fingers extended (PWE-FE) and current hand function are described and compared between children receiving systematic upper-extremity treatment with botulinum neurotoxin type A and intervention programs from before 7 years of age (Group 1, n = 7), those whom for various reasons did not undergo this treatment (Group 2, n = 10), and those not having the option to receive treatment until later during childhood/adolescence (Group 3, n = 8). Group 3 showed more critical and less normal PWE-FE values for both wrists, and poorer hand function scores, particularly compared with Group 1. Findings cautiously suggest that repeated upper-extremity spasticity-reducing treatment and movement training/orthoses from an early age may help prevent critical loss of passive range of motion of the wrist joint flexion/extension and promote hand function development in children with severe CP.

Denervation of the infraspinatus and release of the posterior deltoid muscles in the management of dyskinetic external shoulder rotation in cerebral palsy.

OBJECT: The dyskinetic subtype of cerebral palsy is difficult to manage, and there is no established gold standard for treatment. External rotation of the shoulder(s) is often managed nonsurgically using injections of botulinum toxin A into the external rotator muscles. This article reports a new surgical technique for managing external rotation when botulinum toxin A treatment is not sufficient or possible. METHODS: Six patients with dyskinetic cerebral palsy underwent denervation of the infraspinatus muscle and release of the posterior part of the deltoid muscle. Postoperative questionnaires were given to the patients/caregivers, and video recordings were made both pre- and postoperatively. Preoperative and postoperative Assisting Hand Assessment was possible in only 1 case. RESULTS: Five patients were very satisfied with their outcome. Four patients' video recordings showed improvement in their condition. One patient developed postoperative complications. CONCLUSIONS: The results indicate that denervation of the infraspinatus muscle and posterior deltoid release can be an option for patients with dyskinetic cerebral palsy to manage external rotation of the shoulder when other treatment alternatives are insufficient.

Questionnaire about the adverse events and side effects following botulinum toxin A treatment in patients with cerebral palsy.

Botulinum toxin A (BoNT-A) injections for treatment of spasticity in patients with cerebral palsy (CP) have been used for about two decades. The treatment is considered safe but a low frequency of adverse events (AE) has been reported. A good method to report AEs is necessary to verify the safety of the treatment. We decided to use an active surveillance of treatment-induced harm using a questionnaire we created. We studied the incidence of reported AEs and side effects in patients with CP treated with BoNT-A. We investigated the relationship between the incidence of AEs or side effects and gender, age, weight, total dose, dose per body weight, Gross Motor Function Classification System (GMFCS) and number of treated body parts. Seventy-four patients with CP participated in our study. In 54 (51%) of 105 BoNT-A treatments performed in 45 (61%) patients, there were 95 AEs and side effects reported, out of which 50 were generalized and/or focal distant. Severe AEs occurred in three patients (4%), and their BoNT-A treatment was discontinued. Consecutive collection of the AE and side-effect incidence using our questionnaire can increase the safety of BoNT-A treatment in patients with CP.