Consensus based recommendations for diagnosis and medical management of Poland syndrome (sequence).

BACKGROUND: Poland syndrome (OMIM: 173800) is a disorder in which affected individuals are born with missing or underdeveloped muscles on one side of the body, resulting in abnormalities that can affect the chest, breast, shoulder, arm, and hand. The extent and severity of the abnormalities vary among affected individuals. MAIN BODY: The aim of this work is to provide recommendations for the diagnosis and management of people affected by Poland syndrome based on evidence from literature and experience of health professionals from different medical backgrounds who have followed for several years affected subjects. The literature search was performed in the second half of 2019. Original papers, meta-analyses, reviews, books and guidelines were reviewed and final recommendations were reached by consensus. CONCLUSION: Being Poland syndrome a rare syndrome most recommendations here presented are good clinical practice based on the consensus of the participant experts.

Pseudomonas aeruginosa severe skin infection in a toddler with X-linked agammaglobulinemia due to a novel BTK mutation.

Agammaglobulinemia is a congenital deficit of humoral immunity characterized by a decreased level or complete absence of immunoglobulins and profound reduction of B-lymphocytes associated with an increased risk of life-threatening bacterial infection. We report a case of invasive Pseudomonas aeruginosa severe skin and soft tissue infection treated with vacuum-assisted closure and antibiotics in a toddler with a previously unreported mutation of the Bruton tyrosin kinase gene.

Poland syndrome: A proposed classification system and perspectives on diagnosis and treatment.

Poland Syndrome (PS) is a rare condition, with an estimated incidence of approximately 1 per 30,000 births and encompasses a wide range of severities of chest and upper arm anomalies. The etiology remains unknown, but genetic involvement is suspected. Few radiological investigations have proven useful in the study PS phenotypes and we propose a reference algorithm for guiding pediatricians. Our experience with 245 PS patients in the last 10 years stimulated a phenotypical classification of PS. The management of the different PS types and a therapeutic algorithm according to the phenotypical features of each PS patient are also proposed.

Assessment of copy number variations in 120 patients with Poland syndrome.

BACKGROUND: Poland Syndrome (PS) is a rare congenital disorder presenting with agenesis/hypoplasia of the pectoralis major muscle variably associated with thoracic and/or upper limb anomalies. Most cases are sporadic, but familial recurrence, with different inheritance patterns, has been observed. The genetic etiology of PS remains unknown. Karyotyping and array-comparative genomic hybridization (CGH) analyses can identify genomic imbalances that can clarify the genetic etiology of congenital and neurodevelopmental disorders. We previously reported a chromosome 11 deletion in twin girls with pectoralis muscle hypoplasia and skeletal anomalies, and a chromosome six deletion in a patient presenting a complex phenotype that included pectoralis muscle hypoplasia. However, the contribution of genomic imbalances to PS remains largely unknown. METHODS: To investigate the prevalence of chromosomal imbalances in PS, standard cytogenetic and array-CGH analyses were performed in 120 PS patients. RESULTS: Following the application of stringent filter criteria, 14 rare copy number variations (CNVs) were identified in 14 PS patients in different regions outside known common copy number variations: seven genomic duplications and seven genomic deletions, enclosing the two previously reported PS associated chromosomal deletions. These CNVs ranged from 0.04 to 4.71 Mb in size. Bioinformatic analysis of array-CGH data indicated gene enrichment in pathways involved in cell-cell adhesion, DNA binding and apoptosis processes. The analysis also provided a number of candidate genes possibly causing the developmental defects observed in PS patients, among others REV3L, a gene coding for an error-prone DNA polymerase previously associated with Möbius Syndrome with variable phenotypes including pectoralis muscle agenesis. CONCLUSIONS: A number of rare CNVs were identified in PS patients, and these involve genes that represent candidates for further evaluation. Rare inherited CNVs may contribute to, or represent risk factors of PS in a multifactorial mode of inheritance.

Proposal of the TBN Classification of Thoracic Anomalies and Treatment Algorithm for Poland Syndrome.

BACKGROUND: Poland syndrome is a congenital deformity characterized by unilateral anomalies of pectoralis muscles, breast, nipple, axillary fold, subcutaneous tissue, ribs, and upper limb. The thoracic anomaly, which is the pathognomonic malformation of Poland syndrome, presents a wide phenotype variability and has been classified by different authors. However, these classifications do not include all the possible phenotypes of Poland syndrome. The aim of this study is to propose a simple classification of the whole spectrum of thoracic anomalies and a treatment algorithm that could have a practical value for determining the surgical approach. METHODS: Since 2008, 100 patients have been evaluated by the same plastic surgical team at San Martino Hospital-IST and Istituto Gaslini of Genoa, Italy, using the thorax, breast, nipple-areola complex (TBN) classification. Thoracic anomalies were classified as follows: thorax (T), from T1 (muscle defect only) to T4 (complex deformity with rib and sternal involvement); breast (B), in B1 (hypoplasia) or B2 (amastia); and nipple-areola complex (N), from N1 (dislocation <2 cm) to N3 (athelia). RESULTS: The most frequent thoracic anomalies were T1 (47 percent) and N2 (74 percent), whereas in female patients, B1 was more frequent than B2. The surgical approach to breast and pectoral reconstruction was based not only on the patient's age and sex, but also on the type of anomaly according to the TBN classification. In particular, a two-step approach with tissue expanders was required in N2 and N3 cases, whereas in N1 patients a single step was sufficient. CONCLUSION: The TBN classification can be a useful tool for surgical decision-making according to each specific thoracic anomaly. CLINICAL QUESTION/LEVEL OF EVIDENCE: Diagnostic, IV.

De novo deletion of chromosome 11q12.3 in monozygotic twins affected by Poland Syndrome.

BACKGROUND: Poland Syndrome (PS) is a rare disorder characterized by hypoplasia/aplasia of the pectoralis major muscle, variably associated with thoracic and upper limb anomalies. Familial recurrence has been reported indicating that PS could have a genetic basis, though the genetic mechanisms underlying PS development are still unknown. CASE PRESENTATION: Here we describe a couple of monozygotic (MZ) twin girls, both presenting with Poland Syndrome. They carry a de novo heterozygous 126 Kbp deletion at chromosome 11q12.3 involving 5 genes, four of which, namely HRASLS5, RARRES3, HRASLS2, and PLA2G16, encode proteins that regulate cellular growth, differentiation, and apoptosis, mainly through Ras-mediated signaling pathways. CONCLUSIONS: Phenotype concordance between the monozygotic twin probands provides evidence supporting the genetic control of PS. As genes controlling cell growth and differentiation may be related to morphological defects originating during development, we postulate that the observed chromosome deletion could be causative of the phenotype observed in the twin girls and the deleted genes could play a role in PS development.

The use of propranolol for complicated infantile hemangiomas.

OBJECTIVE: To assess propranolol efficacy and safety in complicated infantile hemangiomas in two different age groups. PATIENTS AND METHODS: We report on 68 infants with infantile hemangiomas treated with oral propranolol at the lowest effective dose at different ages for a period of six months. Inclusion criteria were life-threatening hemangiomas, function-threatening hemangiomas, facial hemangiomas with risk for disfigurement, and extensive and ulcerated hemangiomas. A previously designed safety protocol was applied to all patients. The evolution of all hemangiomas since baseline (pre-therapy) until the end of follow-up was assessed on the basis of clinical features (color, palpable softening, size, and volume) and taken at follow-up visits. RESULTS: Our results showed that propranolol was effective in arresting the proliferative phase and in accelerating the involution of infantile hemangiomas in 92.6% of cases. Propranolol efficacy was clear even when it was started after 12 months of life at low dose; after discontinuation of therapy there was a moderate-to-severe regrowth in 9.3% of cases and a mild regrowth in 22.5%. No adverse events were observed. CONCLUSIONS: Propranolol should be used as first-line medical treatment in all cases of complicated infantile hemangiomas.

The nuss procedure after breast augmentation for female pectus excavatum.

Pectus excavatum, the most common congenital chest wall malformation, has a higher incidence among men. Since 1987, when Donald Nuss performed his technique for the first time, the minimally invasive approach has become the most widely used technique for treating pectus excavatum. Few reported studies have focused on the repair of female pectus excavatum. Women with pectus excavatum often present with breast asymmetry that may require breast augmentation, either before or after pectus excavatum repair. To the authors' knowledge, no reports on the Nuss procedure after breast implant surgery have been published. This report describes the case of a 26-year-old woman who underwent minimally invasive repair after breast implant surgery. The authors believe that for women with severe pectus excavatum, the Nuss procedure should be the first choice for surgical correction. Moreover, for breast implant patients, this technique is absolutely feasible without major complications.

Bilateral endoclose approach for the stabilization of the bar in pectus repair.

BACKGROUND: Mini-invasive repair of pectus excavatum with Nuss technique is the preferred technique in most centers. One of the most important technical points for the final result is the stabilization of the bar, usually obtained by one or more stabilizers and few stitches fixing the bar to some ribs. Our aim is to show how to get the bar more stable by passing bilaterally some stitches around the bar and the ribs close to it. By a right thoracoscopy and a 30-degree optic, we are able to pass the stitches bilaterally by using an Endoclose needle (Covidien Ltd., Hamilton HM, Bermuda). The left hemithorax is visualized from the right side, pushing the optic through the mediastinum following the bar and staying just below it. MATERIALS AND METHODS: We have operated on 230 patients in two centers. We have used only one stabilizer in more than 90% of the patients. In all patients, we have passed four absorbable stitches on the right side, using an Endoclose needle. In the last 45 cases, we have adopted bilateral fixation of the bar by the Endoclose needle. RESULTS: The maneuver takes only around 10 minutes. We did not have complications related to that maneuver. We did not observe destabilization of the bar in those cases. The overall destabilization rate was 1.3%. CONCLUSIONS: We suggest this technique to give the bar more stability on both sides. We think the use of a bilateral stabilizer can be avoided.

A modified technique of ureteroplasty for megaureter in children.

PURPOSE: Excisional ureteroplasty carries the risks of jeopardizing the ureteral vasculature and leakage from the suture. The folding techniques are theoretically less prone to these risks, although they have other disadvantages due to the bulky ureter. According to the literature, these 2 approaches have similar complication rates of 4% to 25%, to include stenosis, reflux and leakage. We introduce a modified ureteroplasty technique with the aim of ensuring effective reduction of the ureteral diameter with minor risks to the vasculature. MATERIALS AND METHODS: A total of 42 consecutive patients underwent ureteroplasty and reimplantation (Cohen 16, Politano-Leadbetter 3, psoas hitch 23) between 1994 and 2004, and were followed for 1 to 9 years. The ureter was opened longitudinally on its less vascularized area. Two parallel longitudinal incisions were made from the luminal side up to the musculature layer, leaving the adventitia untouched. The mucosal aspects lateral to these lines were discarded. The inner layer was closed with a running suture. The adventitial layer was closed with single stitches. RESULTS: No leakage, stenosis or reflux was observed. In 3 ureters persistent dilatation was observed, without obstruction or reflux. CONCLUSIONS: Our modification combines some principles of the 2 classic techniques, with the purpose of decreasing the risks and disadvantages of both. We believe that our approach affords better preservation of the ureteral vasculature because the adventitia is preserved untouched, as well as effective caliber reduction so that the bulking problem is avoided. In addition, the technique is associated with a minor risk of leakage. Our results show that this approach is a valid option for megaureter correction in children.