Hypoplastic Digits Research Articles

Surgical Reconstruction of Unstable, Hypoplastic Fingertips With Allograft and BMP-2 Augmentation: Surgical Technique and Case Series

Objective: Unstable hypoplastic digits can lead to poor function due to instability with pinch and manipulation of objects. The primary goals of surgical reconstruction in these patients are to create 2 stable digits for pinch and improve finger opposition, pinch strength, and digit mobility. In this paper, we present a surgical technique and case series of pediatric patients who underwent surgical reconstruction of unstable/telescoping hypoplastic fingertips using bony allograft augmented with BMP-2. Materials and Methods: A surgical technique for reconstruction of unstable, hypoplastic fingertips was performed using a bony allograft augmented with BMP-2. The series included pediatric patients with hypoplastic digits with instability affecting grip-pinch strength and hand prehension. Results: Ten patients between the ages of 2 and 4 years were included, with 8 thumbs and 2 index fingers being reconstructed. All 10 patients developed clinically stable digits with parent-reported improvements in pinch-grip function including using a switch, opening a bag, and putting on clothes. Postoperative radiographic outcomes did not show any cases of bony overgrowth; 2 patients had evidence of bony resorption though this did not correspond to a significant change in finger length postoperatively. Conclusion: Hypoplastic fingertip reconstruction using bony allograft augmented with BMP-2 is a surgical option for the stabilization of unstable hypoplastic fingertips in congenital hand anomalies. The use of allograft augmented with BMP-2 eliminates donor site morbidity seen with autograft reconstructive options and may limit the concerns with healing/incorporation traditionally reported with allograft use in the literature.

Donor Foot Morbidity Following Nonvascularized Toe Phalanx Transfer Utilizing a New Reconstruction Technique.

Nonvascularized toe phalanx transfer is an accepted surgical option for short and hypoplastic digits in congenital hand abnormalities. However, one of the criticisms of this technique is the donor site morbidity. The purpose of this study was to evaluate donor foot morbidity after nonvascularized toe phalanx transfer using a new donor site reconstruction technique. We retrospectively reviewed 116 nonvascularized toe phalanx transfers in 69 children between 2001 and 2020 in whom the donor foot was reconstructed with a new technique using iliac osteochondral bone graft with periosteum. Feet treated with an isolated donor proximal phalanx of the fourth toe were selected and morbidity was assessed both subjectively and objectively at a minimum of 2 years after surgery. Motion, stability, and alignment of the metatarsophalangeal joint were clinically evaluated. The relative length of the fourth toe to the third toe was measured on a roentgenogram. The satisfaction of the parents for overall function and appearance was evaluated using a visual analog scale. Ninety-four operated feet in 65 patients, including 43 boys and 22 girls, were included. The right foot was evaluated in 52 patients and the left foot in 42 patients. The mean age at operation was 2 years and the mean follow-up period was 7.6 years. Motion at the metatarsophalangeal joint was good at 69% with an average extension of 45 degrees and flexion of 25 degrees. Stability and alignment were good at 95% and 84%, respectively. Only 4 toes had gross instability and 4 toes with poor alignment required revision surgery. Sixty-two toes (66%) maintained proportional length and 9 toes were graded as short. Parental satisfaction was high for appearance as well as function. This newly described technique of using iliac osteochondral bone graft with periosteum to reconstruct toe phalanx donors provided satisfactory results. The function and appearance of the donor foot after a nonvascularized toe phalanx transfer was well preserved. Level IV; therapeutic.

A p53-dependent translational program directs tissue-selective phenotypes in a model of ribosomopathies.

In ribosomopathies, perturbed expression of ribosome components leads to tissue-specific phenotypes. What accounts for such tissue-selective manifestations as a result of mutations in the ribosome, a ubiquitous cellular machine, has remained a mystery. Combining mouse genetics and invivo ribosome profiling, we observe limb-patterning phenotypes in ribosomal protein (RP) haploinsufficient embryos, and we uncover selective translational changes of transcripts that controlling limb development. Surprisingly, both loss of p53, which is activated by RP haploinsufficiency, and augmented protein synthesis rescue these phenotypes. These findings are explained by the finding that p53 functions as a master regulator of protein synthesis, at least in part, through transcriptional activation of 4E-BP1. 4E-BP1, a key translational regulator, in turn, facilitates selective changes in the translatome downstream of p53, and this thereby explains how RP haploinsufficiency may elicit specificity to gene expression. These results provide an integrative model to help understand how invivo tissue-specific phenotypes emerge in ribosomopathies.

Biallelic truncating variants in MAPKAPK5 cause a new developmental disorder involving neurological, cardiac, and facial anomalies combined with synpolydactyly

This study aimed to identify the genetic cause of a new multiple congenital anomalies syndrome observed in three individuals from two unrelated families. Clinical assessment was conducted prenatally and at different postnatal stages. Genetic studies included exome sequencing (ES) combined with single-nucleotide polymorphism (SNP) array based homozygosity mapping and trio ES. Dermal fibroblasts were used for functional assays. A clinically recognizable syndrome characterized by severe developmental delay, variable brain anomalies, congenital heart defects, dysmorphic facial features, and a distinctive type of synpolydactyly with an additional hypoplastic digit between the fourth and fifth digits of hands and/or feet was identified. Additional features included eye abnormalities, hearing impairment, and electroencephalogram anomalies. ES detected different homozygous truncating variants in MAPKAPK5 in both families. Patient-derived cells showed no expression of MAPKAPK5 protein isoforms and reduced levels of the MAPKAPK5-interacting protein ERK3. F-actin recovery after latrunculin B treatment was found to be less efficient in patient-derived fibroblasts than in control cells, supporting a role of MAPKAPK5 in F-actin polymerization. Our data indicate that loss-of-function variants in MAPKAPK5 result in a severe developmental disorder and reveal a major role of this gene in human brain, heart, and limb development.

Collodion newborn with dehydration fever: A rare case report

Ichthyosis is a rare congenital disorder of the skin characterized by the presence of extra covering of tough film-like membrane over the skin leading to fissure formation on stretching. Clinically, newborns present with a membrane with fissures, ectropion, eclabium, and hypoplastic digits. Breakdown of the membrane makes newborns more prone to fluid loss, dehydration, electrolyte imbalance, body temperature instability, and infections leading to high mortality. Here, we report the case of a newborn with this condition presenting with fever, dyselectrolytemia, and dehydration after 48 h of birth managed as dehydration fever after excluding sepsis.

Restoration of Five Digit Hand in Type III B & C Thumb Hypoplasia-A Game Changer in Surgical Management.

Background Hypoplasia of thumb is the second common congenital difference of the thumb, next only to duplication. It may occur as an isolated hand difference or as a part of radial longitudinal deficiency. In approximately 60% of these children, the radius shows hypoplasia. The incidence of thumb hypoplasia is one in 100,000 live births. In 50% of these children, the other hand will also have similar deficiency, although variable in severity. Hypoplasia of thumb has been classified into five major categories, according to the increasing severity of hypoplasia. Type III hypoplasia of thumb is characterized by skeletal hypoplasia involving the first metacarpal and carpometacarpal joint, absent intrinsic muscles and rudimentary extrinsic muscles. It was further subclassified into types A, B & C. Type III B, described by Manske and McCarroll, involves extensive deficiency of extrinsic and intrinsic musculature with aplasia of the metacarpal base. Type III C, described by Buck-Gramcko, has hypoplastic metacarpal head. Methods It is widely believed that reconstruction of Type III B & C hypoplastic thumb will not be functionally useful, and they are often included in the indications for pollicization in thumb hypoplasia. In India, we frequently come across parents, who are not willing to remove the hypoplastic digit. This forced us to find out a way to reconstruct the hypoplastic thumb into a functionally useful digit. We describe our surgical technique of reconstruction of hypoplastic thumbs and our experience in utilization of the technique in five children with Type III B & C hypoplasia of thumb. Carpometacarpal joint of thumb was reconstructed and stabilized with a toe phalangeal transfer in the first stage and an opponensplasty was done in the second stage to improve movement. Results In all the five operated children, our surgical technique yielded a stable thumb which was functional. The donor site morbidity was acceptable. The parents were satisfied with the appearance and functional improvement. Conclusion Surgical reconstruction of hypoplastic thumbs of Type III B & C is possible, and conversion of these poorly developed remnants into a useful digit by our surgical technique is a gamechanger in the management of thumb hypoplasia.

Free Non-vascularized Toe Phalangeal Transfers in Symbrachydactyly: Outcome Analysis

AbstractIntroduction Free nonvascularized toe phalangeal transfer is an established surgical option for the reconstruction of hypoplastic digits. The purpose of the present study was to evaluate our experience with this procedure and to assess bone growth and digit function as well foot morbidity.Material and Methods We retrospectively evaluated the clinical records for all children with symbrachydactyly submitted to free nonvascularized toe phalangeal transfer between 2002 and 2017. A total of 8 patients were included. We summoned the patients to an appointment to clinically assess the range of motion, the stability, and the alignment of the neo-joint. We radiographically measured the final length and the expected percentage of growth of the transferred phalanx. We also evaluated the foot for comorbidities.Results The mean age at the time of the first surgery was 19 months (range: 8–42 months). A total of 20 phalanges were harvested: 16 total proximal phalanges, 2 middle phalanges, 1 subtotal proximal phalanx, and 1 accessory thumb phalanx. The distal part of one proximal phalanx was trimmed because the skin pocket was too tight. Two patients underwent a secondary procedure to release the syndactyly. One transfer required revision surgery due to distal tip necrosis and exposition of the transferred phalanx. In the present series, the overall clinical and radiographic outcomes were compatible to those reported in other studies.Discussion The main limitation of the nonvascularized toe phalanx transfer is the preexisting soft tissue envelope of the finger and the limited growth potential of the transferred bone.Conclusion Irrespective of the amount of growth achieved in the transferred phalanx, the actual transfer and growth attained should not be viewed as the end result, but rather as a means of providing a stable and functional joint.

Long-Term Donor-Site Morbidity After Free, Nonvascularized Toe Phalanx Transfer for Congenital Differences of the Hand

Toe phalanx transplantation is a well-established technique for addressing bony deficiency in the reconstruction of hypoplastic digits in patients with congenital differences of the hand. Prior studies have commented on varying degrees of donor-site morbidity, although assessment of morbidity with validated outcome scores is lacking. This study seeks to evaluate donor-site morbidity after toe phalanx harvest using validated outcome measures. We identified all children who underwent free, nonvascularized toe phalanx transfer to the hand at our institution from 2001 to 2011. We administered the Oxford Ankle Foot Questionnaire for Children (OXAFQ-C) and the Foot and Ankle Ability Measure (FAAM) to all patients, scaling results according to published scoring instructions. Thirty-six patients with 83 toe phalanx transfers were able to be contacted, with a mean follow-up of 5.3 years (range, 18 months-11.2 years). The results of the OXAFQ-C showed mean scores of 99.96% (Physical), 100% (School and Play), and 96.01% (Emotional). The FAAM mean scores were 99.08% (Sports) and 99.17% (Activities of Daily Living). There were no lower extremity complications during the study period. In contrast to varying degrees of donor-site morbidity reported in the current literature, this study demonstrates that toe phalanx harvest causes almost no measurable lower extremity morbidity or dysfunction over the mid- to long-term. Therapeutic IV.

GATAD2B Gene Microdeletion Causing Intellectual Disability Autosomal Dominant Type 18: Case Report and Review of the Literature

Pathogenic variants of the GATAD2B gene (1q21.3) are linked to intellectual disability autosomal dominant type 18 (MRD18; MIM 615074), characterized by dysmorphic features, psychomotor and language delay. We present an 11-year-old female patient with intellectual disability and typical clinical characteristics of MRD18. Chromosomal microarray analysis (CMA) revealed a novel CNV, approximately 200 kb in size and showed that the INTS3 and SLC27A3 genes are completely deleted along with the first 10 exons of the GATAD2B gene. INTS3 encodes the integrator complex subunit 3 and is part of the complex that maintains genome stability; SLC27A3 encodes a fatty acid transporter and has been associated with autism spectrum disorder. GATAD2B haploinsufficiency is associated with the phenotype. Furthermore, the girl had other clinical characteristics not previously described, such as emotional instability, calf hypotrophy, hypoplastic digit pads, tapered thumbs, and anterior earlobe crease. This study highlights the importance of the phenotype-genotype correlation using molecular diagnostic techniques, such as CMA, and its impact on precise diagnosis, treatment, prognosis, and genetic counseling for patients and their families.

Collodion baby treated at a tertiary hospital in Tanzania: a case report

BackgroundThe term “collodion baby” is used to describe a newborn covered with a translucent, parchment-like skin sheet. It is an extremely rare condition with an estimated incidence of 1 in 300,000 live births. Clinically, the baby will present with a collodion membrane with fissures, ectropium, eclabium, and hypoplastic digits. Shedding of the membrane increases risk of dehydration and infection.Case presentationWe present the case of an African baby girl, who died when she was 7-months old, who presented with features of collodion membrane at birth. She later developed hypernatremic dehydration and a constricted band on her lower limb that required urgent surgical release. She stayed in our hospital for 35 days; she was then discharged home after improvement for 6 months of follow-up clinics at Muhimbili National Hospital: neonatal; dermatology; ear, nose, and throat; and physiotherapy units. She died at 7 months of age.ConclusionDespite limited resources, the early survival of these babies can be improved by providing basic care.

MG-102 Coffin-siris syndrome caused by a missense mutation in arid1a

Coffin-Siris syndrome (CSS; OMIM # 135900) is caused by mutations in genes encoding components of the BRMassociated factor (BAF) complex, also known as the mammalian SWItch/sucrose nonfermentable (mSWI/SNF)-like complex. Clinical features are variable and may include hypoplasia of the distal phalanx of the fifth digit, developmental delay, dysmorphic or coarse facial features, growth restriction, and malformations of the brain, heart, and other organs. No widely accepted diagnostic criteria yet exist. Mutations in the ARID1A gene account for approximately 13% of CSS cases with eight patients reported to date. 1 Here we describe a 20-month-old boy with clinical features consistent with CSS, including feeding difficulties, hypotonia, speech delay, CNS anomalies, hypoplastic 5th digits, thick lower lip vermillion, and hypertrichosis. Our patient was found to have a de novo missense mutation (p. Leu1713Pro) in a highly conserved amino acid residue located in one of the leucine-rich motifs of ARID1A . All reported mutations of ARID1A associated with CSS thus far have been truncating, and are believed to be mosaic in lymphocytes. ARID1A heterozygous knock out mice are embryonic lethal, suggesting a vital role in embryonic development. Notably, while mutations in ARID1A noted in cancer are typically nonsense or frameshift, missense mutations in this same leucine-rich motif have been reported. These findings suggest several possibilities including: 1. This mutation resides in a critical position key to the function of ARID1A in human development; 2. This effect may be mild or specific enough to be tolerated and not cause lethality; or 3. This mutation causes moderate instability of the protein leading to a milder clinical presentation. Studies are underway to determine the functional consequences of this missense mutation on ARID1A mRNA and protein production. Reference Kosho T, Okamoto N, Coffin-Siris Syndrome InternationalCollaborators. Genotype-phenotype correlation of Coffin-Siris syndrome causedby mutations in SMARCB1, SMARCA4, SMARCE1, and ARID1A. Am J Med Genet C Semin Med Genet . 2014; 166C (3):262–75

Syndactyly and polydactyly in a mixed-breed dog

Polydactyly is the congenital presence of one or more extra digits. The extra digit often does not contain a full complement of bones. Unilateral syndactyly and polydactyl mixed-breed dog was used as a case study. A three-month old unvaccinated intact female mixed breed dog weighing 8 kg, presented with a deformity of the left forepaw was used for this study. The deformity had been present since birth according to the owner. During physical examination the dog was given a lameness score of 0/5 for the affected limb. A complete blood count, and serum biochemistry did not reveal any abnormalities. Radiographs of both distal forelimbs were obtained. These showed Fused 2nd and 3rd metacarpal bones, a rudimentary metacarpi and a hypoplastic digit located on the axial side of the distal end of the left forelimb. As a result of the lameness score of 0/5 and the owner’s lack of interest, a decision was made to monitor the condition and consider surgery once the dog had grown larger. It seems this is the first case of polydactyly associated with syndactyly and the rudimentary metacarpal bone.

Outcome Measures of Microsurgical Toe Transfers for Reconstruction of Congenital and Traumatic Hand Anomalies

Outcomes data for children undergoing surgical reconstruction of their congenital hand anomalies has been used infrequently or not at all. Some surgeons even contend that children with total absence of digits or hands function perfectly well. Therefore, the purpose of this study was to evaluate and compare the functional outcomes of children who have undergone microsurgical toe-to-hand transfers for reconstruction of congenital and traumatic hand anomalies with the normal pediatric population. A total of 10 adolescents and 15 parents of pediatric and adolescent patients who underwent microsurgical toe-to-hand transfers were assessed using the Pediatric Outcomes Data Collection Instrument (PODCI) survey. Surveys were distributed during routine clinic visits or by mail. Indication and diagnosis were analyzed in relation to the functional outcomes obtained from the survey. Scores of the toe transfer patients group were compared with the scores of the normal pediatric population as well as the effect of patient and parent reporting. Of the 3 survey groups and 6 functional dimensions, there was no statistically significant difference in function between the toe transfer children and the normal pediatric population in 13 of the 18 groups (72%). Adolescent toe transfer patients reported decreased upper extremity function and transfer/basic mobility and parents of adolescents reported decreased upper extremity function, sports/physical function, and global function. Parents significantly underestimated their adolescent children's function in terms of sports/physical function and happiness. Scores did not significantly differ between the congenital or traumatic indications for toe-to-hand transfers. Children with congenital or traumatic missing or hypoplastic digits who undergo reconstruction by microsurgical toe-to-hand transfer can achieve remarkable gains in function, sensation and ability to perform daily activities. This study confirms that a significant percentage of children undergoing reconstruction by microsurgical toe-to-hand transfers have similar functional outcomes assessments when compared with the normal pediatric population. Level III-Therapeutic study.

A Palmar Approach for Insertion of a Free, Nonvascularized Phalangeal Transfer

Free nonvascularized phalangeal transfer from a toe to congenitally hypoplastic digits, is an established procedure in the repertoire of digit reconstruction. The hypoplastic digit is frequently flexed, due to shortage of palmar soft tissues. The phalanx must be transferred intact, with a complete periosteal covering. A new technique of incision and dissection is described utilizing a palmar V approach, closed after skin advancement, as a Y. This permits ample visualization of the digital envelope to receive the phalanx, protection under direct vision of the digital bundles, and simultaneous correction of the deficient palmar skin, without tension.

Long-term Donor Site Morbidity After Free Nonvascularized Toe Phalangeal Transfer

Free nonvascularized toe phalangeal transfer is an established surgical option for the reconstruction of hypoplastic digits. This study assessed long-term morbidity in the feet using this technique. We reviewed 40 children treated between 1991 and 2007 by free nonvascularized toe phalangeal transfer. The diagnosis was digital hypoplasia resulting from symbrachydactyly in 33 cases, constriction ring syndrome in 3 cases, thumb hypoplasia in 3 cases, and perinatal subclavian venous thrombosis in 1 case. The patients were followed up after surgery for a mean of 10 years (range, 3-19 y). The Oxford Ankle Foot Questionnaire was administered to patients and families to assess patient symptoms and patient and parental satisfaction. We assessed toe length ratio, the presence of visible deformity, and distal hypoplasia of the donor toes clinically and radiographically. Emotional problems related to foot appearance were common. We also found functional problems with footwear in some patients. All patients had floppy unstable toes with visible deformity. Increasing foot deformity was seen with growth, which led to deterioration in foot aesthetics, particularly where multiple donor toes had been harvested. We identified distal and middle phalangeal and metatarsal hypoplasia in the donor toes. Donor site morbidity for free toe phalangeal transfer is greater than previously documented. This should be considered during surgical decision making for reconstruction of hypoplastic digits. Preoperative counseling should include discussion regarding possible consequences of phalangeal harvest on donor toes and options for donor site reconstruction. Long-term follow-up of the donor site is essential to accurately assess results. Therapeutic III.

Radial Longitudinal Deficiencies With Hypoplastic/Absent Thumbs and Cutaneous Syndactyly of the Most Radial Digits

To describe radial longitudinal deficiency with hypoplastic or absent thumb and cutaneous syndactyly between the most radial digits. In addition, to discuss the clinical relevance and unique treatment decisions involved in optimizing functional outcomes in these patients. A total of 163 extremities of 122 patients with radial longitudinal deficiencies were reviewed. We reviewed radiographs and clinical images that were available, with most radial hypoplastic digit and cutaneous syndactyly to the adjacent finger. There were 7 hands with this type of deformity. Four cases had a hypoplastic thumb associated with cutaneous syndactyly between the thumb and index finger. Three cases had a deformity in which the thumb was absent and the hypoplastic index finger was syndactylized to the long finger. Proximal and distal radioulnar synostoses were associated with these deformities in 3 patients. Because the most radial digit is severely hypoplastic in this type of deformity, pollicization is usually indicated. However, the pollicization procedure must be modified due to associated syndactyly with different degrees of hypoplasia or absence of the intrinsic muscles. This type of deformity should be distinguished from hypoplastic thumb without syndactyly. Therapeutic IV.

Four limb syndactyly, constriction rings and skin tags; amniotic bands or disorganization-like syndrome

We present a female infant with a combination of finger duplication, amniotic band-like constrictions and extensive syndactyly affecting all four limbs with skin tags. No facial dysmorphic features nor associated malformations were present. Growth and development was normal and there was no family history of congenital abnormalities. The presence of constriction band-like regions on the hands and absent or hypoplastic digits suggests the amniotic deformity, adhesion and mutilation complex. Mutations in the human homologue of the mouse gene disorganization gene may also be the mechanism for the combination of constriction/duplication abnormalities with distant skin tags seen in this patient.

Precision grip function after free toe transfer in children with hypoplastic digits

Precision grip function after free toe transfer in children with hypoplastic digits

Precision grip function after free toe transfer in children with hypoplastic digits

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.

A morpho-etiological description of congenital limb anomalies

BACKGROUNDLimb anomalies rank behind congenital heart disease as the most common birth defects observed in infants. More than 50 classifications for limb anomalies based on morphology and osseous anatomy have been drafted over the past 150 years. The present work aims to provide a concise summary of the most common congenital limb anomalies on a morpho-etiological basis.PATIENTS AND METHODSIn a retrospective study, 70 newborns with anomalies of the upper and/or lower limbs were ascertained through clinical examination, chromosomal analysis, skeletal surveys and other relevant investigations.RESULTSFetal causes of limb anomalies represented 55.8% of the cases in the form of 9 cases (12.9%) with chromosomal aberrations (trisomy 13, 18 and 21, duplication 13q and deletion 22q) and 30 cases (42.9%) with single gene disorders. An environmental etiology for limb anomalies was diagnosed in 11 cases (15.7%) as amniotic band disruption, monozygotic twin with abnormal circulation, vascular disruption (Poland sequence, sirenomelia and general vascular disruption) and an infant with a diabetic mother. Twenty cases (28.5%) had limb anomalies as part of sporadic syndromes of unknown etiology.CONCLUSIONSThe morpho-etiological work-up of limb anomalies adopted in the present study is valuable for detecting the cause of the anomaly and is crucial for its prevention. Prevention can be achieved by proper genetic counseling, which includes recurrence risk estimation and prenatal diagnosis.