Establishment and characterization of ZJUCHi003: an induced pluripotent stem cell line from a patient with Temple-Baraitser/Zimmermann-Laband syndrome carrying KCNH1 c.1070G > A (p.R357Q) variant.

Pathogenic variants of the KCNH1 gene can cause dominant-inherited Temple-Baraitser/Zimmermann-Laband syndrome with severe mental retardation, seizure, gingival hyperplasia and nail hypoplasia. This study established an induced pluripotent stem cell (iPSC) line using urinary cells from a girl with KCNH1 recurrent/hotspot pathogenic variant c.1070G > A (p.R357Q). The cell identity, pluripotency, karyotypic integrity, absence of reprogramming virus and mycoplasma contamination, and differential potential to three germ layers of the iPSC line, named as ZJUCHi003, were characterized and confirmed. Furthermore, ZJUCHi003-derived neurons manifested slower action potential repolarization process and wider action potential half-width than the normal neurons. This cell line will be useful for investigating the pathogenic mechanisms of KCNH1 variants-associated symptoms, as well as for evaluating novel therapeutic approaches.

Molecular diagnosis, clinical evaluation and phenotypic spectrum of Townes-Brocks syndrome: insights from a large Chinese hearing loss cohort.

BACKGROUND: Townes-Brocks syndrome (TBS) is a rare genetic disorder characterised by multiple malformations. Due to its phenotypic heterogeneity and rarity, diagnosis and recognition of TBS can be challenging and there has been a lack of investigation of patients with atypical TBS in large cohorts and delineation of their phenotypic characteristics. METHODS: We screened SALL1 and DACT1 variants using next-generation sequencing in the China Deafness Genetics Consortium (CDGC) cohort enrolling 20 666 unrelated hearing loss (HL) cases. Comprehensive clinical evaluations were conducted on seven members from a three-generation TBS family. Combining data from previously reported cases, we also provided a landscape of phenotypes and genotypes of patients with TBS. RESULTS: We identified five novel and two reported pathogenic/likely pathogenic (P/LP) SALL1 variants from seven families. Audiological features in patients differed in severity and binaural asymmetry. Moreover, previously undocumented malformations in the middle and inner ear were detected in one patient. By comprehensive clinical evaluations, we further provide evidence for the causal relationship between SALL1 variation and certain endocrine abnormalities. Penetrance analysis within familial contexts revealed incomplete penetrance among first-generation patients with TBS and a higher disease burden among their affected offspring. CONCLUSION: This study presents the first insight of genetic screening for patients with TBS in a large HL cohort. We broadened the phenotypic-genotypic spectrum of TBS and our results supported an underestimated prevalence of TBS. Due to the rarity and phenotypic heterogeneity of rare diseases, broader spectrum molecular tests, especially whole genome sequencing, can improve the situation of underdiagnosis and provide effective recommendations for clinical management.

Modified Bilhaut-Cloquet procedure for Wassel type III-IV polydactyly.

BACKGROUND: To investigate the functional and aesthetic results of a new modified Bilhaut-Cloquet procedure for the treatment of Wassel type III-IV thumb polydactyly. METHODS: Thirteen patients with Wassel type III-IV thumb polydactyly who visited the Department of Orthopedics of Hebei Provincial Children's Hospital from 2019 to 2022 were selected. The surgical procedure involved a modified Bilhaut-Cloquet surgery, where two-thirds of the distal part of the dominant finger was retained as the p body of the reconstructed thumb. The triangular bone block of the ablated distal thumb that did not contain the epiphysis and articular cartilage was sutured and fixed, and the neurovascular flap of the ablated distal thumb was used as an augmenting segment of the reconstructed thumb, with the nail bed and nail matrix exquisitely sutured. The evaluation performed according to the Japanese Society for Surgery of the Hand (JSSH) system. RESULTS: All 13 children showed bone healing, no wound infection, nonunion, or deformity healing. None of the children showed a significant reduction in the active and passive mobility of the thumb postoperatively compared with preoperatively. Postoperative evaluation was performed based on the JSSH score, with a mean of 17.15 points (14-19 points), with 11 children rated as excellent and two as good. No severe nail ridges, nail gaps, or nail split deformities of the thumb were observed postoperatively. Postoperative metacarpophalangeal and interphalangeal joint movements were not reduced compared with preoperative movements. All parents were satisfied with the appearance and function of the reconstructed thumb. CONCLUSION: The modified Bilhaut-Cloquet procedure designed in this study was satisfactory for Wassel type III-IV thumb polydactyly without affecting the stability of the interphalangeal joints and preserving joint mobility. The postoperative thumb has a comparable circumference and nail width and was cosmetically and functionally satisfactory, especially for the asymmetric two thumbs, which achieved favorable results.

Complications after radial polydactyly surgery: analysis, prevention and management.

Long-term follow-up after surgical correction of patients with radial polydactyly might reveal unexpected or undesired outcomes that are accentuated by growth. It should be stressed that assessment of outcomes differs considerably by the system used. Preoperative examination can elucidate the underlying pathological anatomy of these anomalies and consequently, these anatomical differences should be corrected as much as possible during the first operation to prevent worse outcomes at long-term follow-up. In various long-term studies, the reoperation rate was in the range of 7%-28%, with the most common reasons being deviation, instability, nail deformity and suboptimal appearance. Most unfavourable results occur during growth and are frequently revealed only at longer-term follow-up. Concentration of care to a few centres is advised since these malformations occur in small numbers and experienced surgeons tend to have better results. Consensus on the used assessment system and multicentred studies are essential in future to better understand how we can prevent reoperations.

An alternative method to reconstruct grade-3 hypoplastic thumb by hemi-metacarpal transfer.

We designed a new method using hemi-longitudinal second metacarpal bone to reconstruct grade-3 hypoplastic thumbs. Seven patients were treated in two stages. In the first stage, the second metacarpal was split longitudinally and transferred to reconstruct the first metacarpal. In the second stage, opponensplasty was performed by transferring the FDS tendon. Bone union was achieved in all cases. All patients could oppose to their middle finger at least. They managed to do daily activities such as writing, eating, using smartphones and so on. This is a useful procedure to preserve a 5-digit hand with good function in treating grade-3 hypoplastic thumbs, with no harm to the foot and no need for vascular anastomosis. LEVEL OF EVIDENCE: IV.

Transverse snuffbox perforator flap for a first-web contracture: an anatomical study and case report.

This cadaveric study describes a dorsal wrist transverse elliptical cutaneous flap, based on radial artery cutaneous perforators in the region of the snuffbox. The flap was then successfully used in a child with thumb hypoplasia and severe first-web contracture.

Clinical evidence of the association between radial longitudinal deficiency and radial polydactyly: a case series.

Radial longitudinal deficiency (RLD) is commonly associated with thumb hypoplasia. The association between RLD and radial polydactyly (RP) is uncommon, but case reports or case series have been reported. We report our experience of managing patients with this association. A total of 97 patients with RLD were seen in our department, of which six were children with concomitant RLD and RP. Four children had both RLD and RP in the same limb; of them, three also had RLD in the contralateral limb. The mean age at presentation was 11.6 months. Awareness of this association alerts the clinician to look for RLD in the presence of RP and vice versa. This case series supports recent experimental and clinical evidence that RP and RLD may be part of the same developmental spectrum. Further studies may guide its inclusion as a possible new category in the Oberg-Manske-Tonkin (OMT) classification of congenital upper-limb anomalies.Level of evidence: IV.

Reconstruction of Type IIIB Thumb Hypoplasia Using a Vascularized Hemi-Metatarsal Composite Tissue Flap.

BACKGROUND: The aim of this study was to determine the clinical outcomes of vascularized hemi-metatarsal composite tissue transfer for the reconstruction of type IIIB hypoplastic thumbs. METHODS: Twenty-eight patients with type IIIB hypoplastic thumbs treated with vascularized hemi-metatarsal composite tissue transfer were included in this retrospective study with a mean follow-up of 2.4 years. Preoperative digital subtraction angiography was performed to examine the vessel variance. Clinical measures included grip and pinch strength, scar status, and Kapandji thumb opposition score. Subjective Pediatric Outcomes Data Collection Instrument scores and parent satisfaction were also evaluated. RESULTS: Radial arteries were hypoplastic in 82.1% of the cases, and the common palmar digital artery was chosen as the recipient vessel for the tissue transfer. There was no neurovascular complication. The only donor-site complication was a metatarsal fracture that healed with casting. Key pinch and tripod pinch were 29.5% and 45.8% of the normal side, respectively. The mean grip strength was 51.7% of the unaffected side. The mean Kapandji score was 6. The Pediatric Outcomes Data Collection Instrument scores were high for global function; upper extremity function; transfer; and basic mobility, happiness, and comfort. The Vancouver Scar Scale showed an average score of 2.1. All parents were satisfied with the clinical outcomes. CONCLUSION: Vascularized hemi-metatarsal composite tissue transfer for type IIIB thumb hypoplasia can provide improved subjective outcomes and is a feasible method for the attainment of a five-digit hand. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Chromosomal Microarray Analysis Identifies a Novel SALL1 Deletion, Supporting the Association of Haploinsufficiency with a Mild Phenotype of Townes-Brocks Syndrome.

SALL1 heterozygous pathogenic variants cause Townes-Brocks syndrome (TBS), a condition with variable clinical presentation. The main features are a stenotic or imperforate anus, dysplastic ears, and thumb malformations, and other common concerns are hearing impairments, foot malformations, and renal and heart defects. Most of the pathogenic SALL1 variants are nonsense and frameshift, likely escaping nonsense-mediated mRNA decay and causing disease via a dominant-negative mechanism. Haploinsufficiency may result in mild phenotypes, but only four families with distinct SALL1 deletions have been reported to date, with a few more being of larger size and also affecting neighboring genes. We report on a family with autosomal dominant hearing impairment and mild anal and skeletal anomalies, in whom a novel 350 kb SALL1 deletion, spanning exon 1 and the upstream region, was identified by array comparative genomic hybridization. We review the clinical findings of known individuals with SALL1 deletions and point out that the overall phenotype is milder, especially when compared with individuals who carry the recurrent p.Arg276Ter mutation, but with a possible higher risk of developmental delay. Chromosomal microarray analysis is still a valuable tool in the identification of atypical/mild TBS cases, which are likely underestimated.

Surgical Results of Ulnar Component Excision and Radial Component Reconstruction in Patients With Preaxial Polydactyly of the Hand.

PURPOSE: Resection of the underdeveloped digit and reconstruction of the robust digit is the standard treatment option for preaxial polydactyly of the hand. As an underdeveloped digit, the radial component is usually excised, whereas the ulnar component excision is rarely needed. This study aimed to evaluate the surgical results of ulnar component excision and radial component reconstruction in patients with preaxial polydactyly of the hand. METHODS: We retrospectively reviewed the medical records and radiographs of 809 patients (861 thumbs) who underwent surgery for preaxial polydactyly of the hand from November 2006 to June 2018. Among these, 22 (2.6%) thumbs in which the ulnar component was more hypoplastic or had more severe deformities than the radial component were treated with ulnar component excision and radial component reconstruction. The mean follow-up duration was 49 months (range, 12-142 months). We evaluated the Japanese Society for Surgery of the Hand scores and whether the patients were satisfied with the thumb function and appearance at the final follow-up. We also recorded any complications, such as reoperation. RESULTS: The mean Japanese Society for Surgery of the Hand score was 12.8 (range, 5-17). Six patients had poor results, 7 had fair results, and 2 had good results; however, none of the patients had an excellent result. Satisfaction with thumb function and appearance was reported in 11 (50%) and 6 (27%) cases, respectively. Thirteen of 22 (59.1%) cases involved reoperations, and the most common reason for reoperation was interphalangeal joint deviation of the remaining thumb. CONCLUSIONS: Ulnar component excision and radial component reconstruction are rare operative choices in preaxial polydactyly of the hand. Surgeons and patients should be aware that a considerable number of patients treated with this method required reoperations and had low clinical outcome scores. TYPE OF STUDY/ LEVEL OF EVIDENCE: Prognostic IV.

Surgical Technique and Outcomes of Reconstruction for Blauth Type III Thumb Hypoplasia.

BACKGROUND: Historically, amputation and pollicization has been the recommended surgical treatment for Blauth type III hypoplastic thumbs. However, due to aesthetic objections or cultural preferences, some parents seek out alternative surgical options. The present study describes a nontraditional technique that preserves and augments the hypoplastic thumb. METHODS: Patient charts were retrospectively reviewed to identify patients with Blauth type III hypoplastic thumbs who underwent thumb reconstruction at our institution from 2008 to 2018. The reconstruction procedure involved toe phalanx transfer, staged tendon transfers, and lengthening as needed. Motion was assessed categorically as ability to flex, extend, or oppose the thumb. Functionality was assessed as ability to pinch and grasp with the surgical hand. Patient- or parent-reported improvement in thumb function was also recorded. RESULTS: Of the 13 patients, 100% could flex, extend, and oppose the thumb to some degree. Eleven patients (85%) had functional one-handed grasp, and 9 (69%) had a functional pinch. Eleven patients (85%) reported no functional limitations of the operative hand. Thirteen patients (100%) reported improvement in hand function after surgery as compared to pre-operatively. There were 2 minor complications (15%), both of which resolved after intervention. No patients experienced donor-site morbidity. CONCLUSIONS: Reconstruction of Blauth III thumbs is a nontraditional technique that allows for digit retention by salvaging the hypoplastic thumb. In the present study, the majority of patients had functional thumbs and all reported postoperative improvement. Overall, our results suggest that reconstruction is a viable surgical option for Blauth III hypoplastic thumbs.

Nonvascularized Iliac Crest Bone Graft for Reconstruction of the First Metacarpal in Type IIIB Thumb Hypoplasia: A Radiographic Follow-Up Study.

PURPOSE: To present a radiographic follow-up study of the use of a nonvascularized iliac crest bone graft as a treatment for modified Blauth type IIIB thumb hypoplasia. METHODS: From January 2015 to December 2019, nonvascularized iliac crest bone grafts were used to reconstruct the first metacarpal in 23 cases with type IIIB thumbs. The average follow-up duration was 1.9 years (range 1.0-3.9 years). We evaluated the patients' serial x-rays and measured the width and length changes of the reconstructed first metacarpals. RESULTS: Survival of the graft, judged radiographically, was achieved in 20 cases (20/23, 87%), with an average reduction of 33% in the width of the graft. Shortening of the graft (average 2.3 mm, range 0.1-5.6 mm) was noted in 11 of the 20 cases, and an increase in the length of the graft (average 4.2 mm, range 0.7-8.6 mm) was observed in the other 9. Bone graft failure (3/23, 13%) occurred in 3 cases because of significant bone resorption. CONCLUSIONS: For type IIIB thumb hypoplasia, a nonvascularized iliac crest bone graft was a feasible method to reconstruct the first metacarpal, with a 13% risk of graft failure, 33% average reduction in graft width, and 55% reduction in graft length. However, in cultures that value the preservation of a 5-digit hand, this technique may provide an alternative to excision with index pollicization. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

A fully capable pianist with a congenital bilateral agenesis of extensor pollicis brevis muscle.

A 28-year-old male musical student has been presented with visible inability of active abduction and extension of the thumbs in both hands beyond the neutral position. The student has not been previously diagnosed and claimed no history of trauma or surgical procedures in the area of hands and no family history of such disabilities. The student remained capable of playing on keyboard instruments on high level due to compensation by hyperextension of the interphalangeal joint of both thumbs and showed no increased frequency of the injuries or playing-related disorders. The ultrasound and magnetic resonance imaging showed complete bilateral agenesis of extensor pollicis brevis muscles and was classified as isolated congenital clasped thumb syndrome. Due to the age of the student and the agenesis of the muscles the conservative treatment was deemed inadequate and due to high functionality of the student as a musician and unforeseeable results it might have on a musician's career, surgical treatment has been disadvised.

Update of surgical treatment of polydactyly.

PURPOSE OF REVIEW: Polydactyly presents with variable extent of duplication and may involve preaxial/radial (hand)/medial (foot), postaxial/ulnar (hand)/lateral (foot) or central duplication. This review will summarize recent advancements in the surgical management of this common entity. RECENT FINDINGS: Modifications to classification systems aim to help guide surgical management of polydactyly. Attempts have been made at quantifying preoperative angulation of the duplicated digits to minimize the chance of residual or recurrent deformity after surgical reconstruction. As a result, consideration should be given to the need for soft tissue correction vs. osteotomy to optimize the clinical outcome. On-top plasty is an option that may be beneficial in 'unequal' preaxial polydactyly, where neither duplicate is preferred on its own. SUMMARY: Polydactyly is one of the most common congenital anomalies in the hands and feet. Determination of surgical intervention often begins with classification systems that exist, which primarily separate these into preaxial, postaxial, and central. Referral for surgical consideration is indicated, given the management is often surgical.

Triphalangeal thump, thumb duplication, and syndactyly: The first case report in the literature.

RATIONALE: Triphalangeal thumb (TPT) is a rare congenital malformation where the thumb has three phalanges instead of two. Syndactyly is a condition in which children are born with fused or webbed fingers. The combination of TPT, Syndactyly, and thumb duplication is extremely rare, especially when these deformities are combined in one hand. PATIENT CONCERNS: Hand abnormalities and polydactyl have been reported in a 1-year-old boy. DIAGNOSIS: A clinical examination reveals two thumb duplications, finger fusion (Syndactyly), and a thumb with three phalanges (TPT). The diagnosis was based on clinical findings and an X-ray image of the hand. INTERVENTIONS: The Z-plasty method was used to remove the adhesion between the thumb and forefinger, as well as the removal of the medial and distal phalanx of the thumb's medial tip. OUTCOMES: The patient was followed for 2 months and found him in good health. To authors' knowledge, we described an unusual case from Syria, considered the first in medical history. LESSONS LEARNED: General and plastic surgeons should be aware about this unusual mix of the three abnormalities. The family history must also be carefully investigated to explore the occurrence of hereditary illnesses.

Congenital difference of the hand and foot: Pediatric macrodactyly.

BACKGROUND: Macrodactyly is a very rare congenital difference that affects hands and feet with significant developmental and psychological implications. Macrodactyly is attributed to a somatic mutation in PIK3CA, a component of the mTOR pathway-related overgrowth disorders. Other medical conditions have been associated with macrodactyly (e.g., neurofibromatosis and Proteus syndrome). A thorough investigation of the presence of these conditions should be undertaken by the multidisciplinary team. The aim of this study is to summarize the main clinical characteristics and associated conditions, with an emphasis on diagnosis and surgical treatment options. MATERIALS AND METHODS: We present several clinical cases after a retrospective chart review of macrodactyly cases and a comprehensive literature review. RESULTS: The indications for surgery include peripheral compressive neuropathies (e.g., carpal tunnel syndrome), grotesque enlargement interfering with function, psychosocial distress due to the deformity, and macrodystrophic lipomatosis with proximal upper limb involvement. The main surgical treatment options are categorized as follows: digit reduction (e.g., soft tissue debulking, skeletal shortening/ terminalization, Barsky procedure, and Tsuge technique), limitation of growth (digital nerve stripping and epiphysiodesis), and correction of deviation (wedge or angulation osteotomy, arthrodesis, Millesi procedure for thumb macrodactyly correction, toe-to-hand transfer, ray resection, and combination of bony reduction and soft tissue debulking). CONCLUSIONS: Macrodactyly correction requires surgical experience and an individualized approach. Treatment is primarily surgical; however, efforts are being made to delineate the root cause of macrodactyly and provide nonoperative management.

Satisfaction with hand appearance in children with index pollicization for thumb hypoplasia.

Although the primary aim of pollicization is to augment function, aesthetic improvement is an important secondary aim. Satisfaction with hand appearance in children with index pollicization for thumb hypoplasia was evaluated in 18 patients at an average of 7.5 years after surgery. Patients and their parents rated the appearance of their operated hand using a 10-point visual analogue scale (VAS). Four independent surgeons and 16 non-surgeon observers also rated the hands after reviewing standardized photographs of each child. The median patient-reported and parent-reported scores were 9 for both groups (IQR: 7-10) with a trend for children 12 years and older, to report lower satisfaction with appearance. The non-surgeon group assessments varied more for a given hand than the surgeons' assessments, though when scores were averaged within these groups for each hand, there was a high degree of correlation between the two groups. Surprisingly, the patient's own assessment showed a trend towards negative correlation when compared with the average rating of the non-surgeon assessors, suggesting that patients' own assessment of their hand's appearance is more affected by subjective factors than the objective physical outcome.

Mid-term to Long-term Follow-up Results of Reconstruction for Thumb Radial Polydactyly.

BACKGROUND: Preaxial or radial polydactyly is one of the most common hand congenital anomalies in newborns. Contemporary reconstruction methods include ligament reconstruction, excision of the polydactylous thumb, osteotomy, and other surgical techniques according to the type of polydactyly. The purpose of this study was to report mid-term to long-term reconstruction results for thumb (radial) polydactyly. METHODS: We retrospectively reviewed the medical records of patients who underwent reconstruction surgery for preaxial polydactyly. Clinical outcomes, including the range of motion (ROM), pain, and complications, were evaluated. We assessed the final radiographs of the reconstructed thumb to identify the potential development of arthritis or other remaining deformities. After excluding cases without a simple radiograph and cases with a short follow-up period of fewer than 5 years, 26 thumbs were included. The surgical technique followed including excision of polydactylout thumb was tailored to the type of polydactyly. If the nail size of the thumbs was similar, the Bilhaut-Cloquet method was preferred. RESULTS: The mean age of the patients at the surgery and final follow-up was 14.9 months (range: 8 to 30 mo) and 11.9 years (range: 5.8 to 19.3 y), respectively. The mean follow-up was 128.8 months years (range: 60 to 219 mo), and the mean ROM of the thumb was 32.7 and 57.5 degrees in the distal interphalangeal joint (DIP) and metacarpophalangeal (MP) joint, respectively. Ulnar or radial side instability was prominent in 7 patients in the involved joints (26.9%). One patient underwent interphalangeal (IP) fusion for extension lag with pain. The radiologic evaluation revealed that 2 patients developed radiographic evidence of IP joint arthritis (7.7%). Radial deviation of the MP or IP joint existed in 13 cases (range: 5 to 40 degrees) (50.0%), and ulnar deviation of the MP or IP joint existed in 2 cases (range: 19 to 20 degrees) (7.7%). CONCLUSIONS: In mid-term to long-term experience, sequelae such as joint instability, joint stiffness, and remaining deformity cannot be neglected. An unstable MP joint may result if the DIP joint remains stiff or has a lower ROM. LEVEL OF EVIDENCE: Level IV-therapeutic studies.