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The chromatin remodeling AT-Rich interaction domain containing 1B protein (ARID1B) also known as BAF-associated factor, 250-KD, B (BAF250B) codified by the ARID1B gene (MIM#614556), is a small subunit of the mammalian SWI/SNF or BAF complex, an ATP-dependent protein machinery which is able to activate or repress gene transcription, allowing protein access to histones through DNA relaxed conformation. ARID1B gene mutations have been associated with two hereditary syndromic conditions, namely Coffin-Siris (CSS, MIM#135900) and Nicolaides-Baraitser syndromes (NCBRS, MIM#601358), characterized by neurodevelopment delay, craniofacial dysmorphisms and skeletal anomalies. Furthermore, intellectual impairment and central nervous system (CNS) alterations, comprising abnormal corpus callosum, have been associated with mutations in this gene. Moreover, ARID1B anomalies resulted to be involved in neoplastic events and Hirschprung disease. Here we report on two monozygotic male twins, displaying clinical appearance strikingly resembling NCBRS and CSS phenotype, who resulted carriers of a novel 6q25.3 microdeletion, encompassing only part of the ARID1B gene. The deleted segment was not inherited from the only parent tested and afflicted the first exons of the gene, coding for protein disordered region. We also provide, for the first time, a review of previously published ARID1B mutated patients with NCBRS and CSS phenotype and a computer-assisted dysmorphology analysis of NCBRS and ARID1B related CSS individuals, through the Face2Gene suite, confirming the existence of highly overlapping facial gestalt of both conditions. The present findings indicate that ARID1B could be considered a contributing gene not only in CSS but also in NCBRS phenotype, although the main gene related to this latter condition is the SMARCA2 gene (MIM#600014), another component of the BAF complex. So, ARID1B study should be considered in such individuals., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)

Purpose: This study was designed to evaluate thumb growth after surgical management of a duplicate thumb and investigate its developmental pattern., Methods: We compared the thumbs and index fingers of 486 normal children (aged 1-18 y) (group A) with 15 children showing radial polydactyly (group B). All duplicate thumbs were treated with excision of the radial thumb and reconstruction of the ulnar thumb. Radiographs of groups A and B were used to compute the thumb-to-index finger length ratio and width ratio, and the thumb-to-index finger phalanx length ratio and phalanx width ratio., Results: In group A, the length ratio, width ratio, phalanx length ratio, and phalanx width ratio did not change with age, and remained constant in males and females. In group B, after an average follow-up period of 41.0 months, the original findings were also similar to the final ratios. In group B, only the phalanx width ratio was obviously smaller than normal., Conclusions: A permanent developmental stability exists between the thumb and the index finger, even in patients with radial polydactyly. The development of the retained digit is not influenced by the ablation of the extra digit., Type of Study/level of Evidence: Therapeutic IV., (Copyright © 2016 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.)

Purpose: To evaluate outcome and function of the reconstructed basilar thumb joint after index finger pollicization in patients presenting congenital thumb deficiency., Methods: Plain radiographs and 4-dimensional dynamic volume computed tomography scan were used to evaluate the outcome of 23 pollicizations performed on 14 children between 1996 and 2009. The mean follow-up was 8 years. Patients performed continuous movements of thumb opposition during the imaging studies. Four-dimensional scan images made it possible to visualize mobility within the reconstructed joint., Results: In 14 cases, union occurred in the metacarpal head/metacarpal base interface. In the 9 other cases, there was a nonunion at this interface. The reconstructed joint was mobile in 20 cases, including 3 in which there was also mobility at the site of the nonunion. In 3 cases in our series, mobility was present only at the site of the nonunion, between the base and the head of the second metacarpal. Remodeling and flattening out of the metacarpal head occurred in 16 of 23 cases. The transposed metacarpal head remained spherical in 7 cases., Conclusions: The reconstructed joint adapts, both morphologically and functionally, allowing movement on all 3 spatial planes. Existing mechanical constraints on the reconstructed joint may explain its remodeled appearance., Type of Study/level of Evidence: Therapeutic IV., (Copyright © 2016 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.)

A 16p13.3 duplication syndrome has been recently suggested to be a novel recognizable syndrome as a reciprocal microduplication disease of Rubinstein-Taybi syndrome. The CREBBP gene is believed to be the dosage-sensitive critical gene responsible for the reciprocal duplication and deletion syndrome. Descriptions so far have been de novo. Here, we report a very rare case of a maternally inherited a -1 Mb sized duplication on 16p13.3 identified by SNP array testing. The patient showed moderate intellectual disability, normal growth, and characteristic facial features. The patient's mother also had mild intellectual disability, normal growth, camptodactyly, proximally implanted small thumbs, and distinctive facial features. The study provides additional information that furthers the understanding and delineation of 16p13.3 duplication syndrome., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

Purpose: To measure and compare hand function for children with normal hand development, congenital hand differences (CHD), and neuromuscular disease (NMD) using a function test with touch screen technology designed as an iPhone application., Methods: We measured touch screen hand function in 201 children including 113 with normal hand formation, 43 with CHD, and 45 with NMD. The touch screen test was developed on the iOS platform using an Apple iPhone 4. We measured 4 tasks: touching dots on a 3 × 4 grid, dragging shapes, use of the touch screen camera, and typing a line of text. The test takes 60 to 120 seconds and includes a pretest to familiarize the subject with the format. Each task is timed independently and the overall time is recorded., Results: Children with normal hand development took less time to complete all 4 subtests with increasing age. When comparing children with normal hand development with those with CHD or NMD, in children aged less than 5 years we saw minimal differences; those aged 5 to 6 years with CHD took significantly longer total time; those aged 7 to 8 years with NMD took significantly longer total time; those aged 9 to 11 years with CHD took significantly longer total time; and those aged 12 years and older with NMD took significantly longer total time., Conclusions: Touch screen technology has becoming increasingly relevant to hand function in modern society. This study provides standardized age norms and shows that our test discriminates between normal hand development and that in children with CHD or NMD., Type of Study/level of Evidence: Diagnostic III., (Copyright © 2015 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.)

Purpose: To obtain epidemiologic data on the Linburg-Comstock anomaly in Malaysia and to study the effect of the anomaly on key pinch strength., Methods: We examined 292 healthy subjects (162 female and 130 male) bilaterally for the presence of the Linburg-Comstock anomaly. Each subject's key pinch strength was measured bilaterally using a pinch meter., Results: The Linburg-Comstock anomaly was present in 101 of the 292 subjects (35%). Sixty-five subjects (22%) had it unilaterally, and 36 subjects (6%) had it bilaterally. The anomaly was associated with superior key pinch strength., Conclusions: The study provides epidemiologic data of this anomaly in Malaysia and considers its anatomical influence on key pinch strength., Type of Study/level of Evidence: Prognostic IV., (Copyright © 2012 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.)

The pathogenesis of hypertension is multi-factorial, involving many of the systems contributing to blood pressure homeostasis including the vasculature, kidneys, central, and sympathetic nervous systems, along with various hormonal regulators. However, over the years, many studies have indicated a predominant importance of the kidney in blood pressure homeostasis and hypertension. This work has established the notion that the kidney is a key determinant of the chronic level of intra-arterial pressure playing a major role in the pathogenesis of hypertension. Therefore, this review will focus on recent work using genetically modified mouse models addressing the role of the kidney in hypertension. In particular, human genetic studies of Mendelian disorders with major impact on blood pressure homeostasis have provided powerful evidence for a role of the kidney in hypertension. Of the approximately 20 genes identified as causal in these disorders, virtually all have an effect on the control of solute transport in the kidney. As such, we have especially focused on generation of mouse models addressing the nature of these specific molecular defects in nephron function that produce an alteration in blood pressure., (Copyright © 2012 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Salt-sensitive forms of hypertension have received considerable renewed attention in recent years. This article focuses on 2 main forms of salt-sensitive hypertension (familial or genetic primary aldosteronism [PA] and Gordon syndrome) and the current state of knowledge regarding their genetic bases. The glucocorticoid-remediable form of familial PA (familial hyperaldosteronism type I) is dealt with only briefly because it is covered in depth elsewhere., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Embryonic heart and limb development are closely related with >100 known inherited disorders affecting both. Common limb defects include duplication, deficiencies, and hypoplasia. Ventricular septal defects and atrial septal defects are the commonest associated cardiac conditions. A positive association exists between heart defects and limb disorders when these disorders are analyzed separately. Closer associations exist between heart defects and upper limb defects compared with lower limb defects. The majority of limb defects occur in the more distal parts of the affected limb. Genes expressed in both the heart and limb development include TGF-beta, BMP4, Msx transcription factor, HAND gene, retinoic acid receptor, and sonic hedgehog gene. Radial ray-heart syndromes are better described than ulnar ray-hand syndromes. There is significant variability of malformations. Partial phenocopies that are not genetically linked are well documented. An appreciation of ulnar anomalies should always provoke an evaluation of the heart for potential abnormalities. Although heart-hand syndromes are rare, valvular abnormalities and aortic aneurysms can lead to significant complications unless identified in time. The presence of radial or ulnar ray anomalies merit a detailed cardiac examination and a low threshold for cardiac imaging.

Although toe-to-hand transfer has a defined role in the management of congenital hand deformities, it remains unclear how well children integrate the transferred digits into physiological grasping. We analysed fingertip forces in the precision grip of 13 patients when lifting a test object more than three years after free toe transfer for absent or hypoplastic digits. Clinically, most patients showed normal sensibility of transferred digits, but active motion and pinch strength were limited as compared to the normal hand. For the control of fingertip forces, two key features of the normal two-digit opposition grip were seen in all operated hands: adaptation of grip force to object weight and parallel coordination of lift and grip forces. These physiological grasping strategies developed independently of the patients' age at the time of operation, which ranged from one to 13 years. In four patients, we observed increased tangential load forces with the operated hand due to misalignments in the application of fingertips on the grasp surfaces. Such forces lead to increased grip force requirements on both fingers that may overload transferred digits with limited motor function. The need for optimal alignment of the grip axis during toe-transfer surgery is emphasised.

Congenital swan neck deformity is a rare condition, secondary to congenital laxity of the palmar plate of the proximal interphalangeal joint. Here, we describe a new surgical method which is based on the palmar plate reinforcement using the Mitek mini anchor system (Mitek Surgical Products Inc., Norwood, MA, USA). Four fingers of a patient with congenital swan neck deformities were corrected with this technique at two stages. First, the anchor was inserted into the volar surface of the proximal phalanx. The two sutures of the anchor system were then crossed the PIP joint in a V fashion. Two holes, 5mm apart from each other, were created through the middle phalanx distal to both insertion points of superficial flexor tendon. The suture ends of the anchor were passed through these holes from the volar to the dorsal side of the middle phalanx and then turned around the edges of the bone to the volar surface. They were tied to each other as the PIP joint was stabilised at 20 degrees flexion by use of a K-wire. The K-wire was removed 21 days later and a rehabilitation program was then initiated. A second operation for the two fingers of the opposite hand was performed 2 months after the first operation. No postoperative complications were encountered. At 2 years follow-up, the active range of motion was within normal limits at PIP and DIP joints of all four fingers without any recurrence of hyperextension or hyperflexion. The final result was satisfactory regarding both the functional and cosmetic aspects. The Mitek mini anchor offers a practical, reliable and functional reconstruction of the volar plate in the management of congenital swan neck deformities. We believe that it may also be used for the acquired deformities.

Sign language is the fourth most commonly used language in the United States. Despite the frequent need for this unique upper limb function, little is known regarding the demands and consequences of signing. This article (1) reviews 15 signers with upper limb abnormalities to determine how the abnormalities affect their signing, and (2) explores overuse syndromes in six sign language interpreters. Because of the way the sign language is constructed, only the most severe, bilateral limb abnormalities affect signing, and no extraordinary measures beyond standard, high quality hand care is required to improve function. To treat overuse syndromes in sign language interpreters, customary conservative treatments have generally been useful, but prevention is greatly preferable to treatment.

A personal technique is described for reconstruction of the first web-space in congenital hand deformities with severe adduction of the thumb. The technique is based on the use of two local rotation flaps, one designed on the thenar area and the other on the radial half of the back of the hand. Seven patients were treated with such a technique and followed up for an average of 32 months. Excellent results were obtained in five cases.