Ectrodactyly Research Articles

Myocysticercosis Presenting as Incomplete Claw Hand: A Rare Presentation of Cysticercus

Human cysticercosis is an infection with the larval form of Taenia solium that commonly involves the central nervous system. Due to the infection, isolated muscular involvement is rare, and very few cases have been reported in the literature. Hereby, the authors present a rare instance of isolated muscular cysticercosis in a 15-year-old girl, resulting in an incomplete claw hand due to the compression of both the ulnar and median nerves. The patient had been experiencing swelling on the anterior aspect of her left forearm for eight months, with recent aggravation. The swelling was gradually followed by an inability to fully extend the middle and ring fingers for the past six months. The patient’s laboratory results were within normal limits, and ultrasound and Magnetic Resonance Imaging (MRI) of the forearm confirmed the presence of cysticercosis. The treatment plan included a course of oral steroids and antihelminthic drugs, along with physiotherapy. In present case, the patient’s condition significantly improved with conservative management. The present case illustrates the diagnostic challenges due to the vague clinical presentation and unfamiliarity of clinicians with present entity, making it difficult to diagnose when seen as an isolated cyst. The unique manifestations of muscular cysticercosis emphasise the importance of early detection and proper management

Cobb Syndrome, A Rare Disease – Case Report

Cobb syndrome is a rare genetic disorder characterized by dermatomal pattern, with corresponding muscular, osseous, paraspinal, and/or spinal vascular lesions occurring at the same body somite (metamere). It is also known as spinal arteriovenous metameric syndrome (SAMS) and cutaneous meningospinal angiomatosis. We present a case of a 36 years old male presented to OPD with Complain of progressive weakness of Right upper limb for 5 years. On examination, Patient had large cutaneous port wine stain on the right side of the chest, nape of neck, and along the whole right upper limb in a dermatomal distribution with ulnar claw hand wasting of thenar muscles on right side. MRI cervical spine with contrast showed aggressive vertebral hemangioma involving anterior and posterior arch of C1 vertebra, vertebral body of C2 to C5, right half of vertebral body of C2 and C6 and right pedicle of C2 to C5 vertebra. Abnormal thickened and T2WI /STIR hyperintense skin and subcutaneous tissue involving right half of scalp and right half of neck which showing post contrast enhancement, possibility of subcutaneous hemangioma. Cobb syndrome was diagnosed based on the dermatomal distribution of the cutaneous vascular lesions and the corresponding vertebral, epidural, and paraspinal vascular lesions occurring at the same metamere. Treatment decision is guided by the patient’s symptoms and imaging features.

Acrorenal Syndrome: Case Series

Acral (limb) and renal anomalies occur together as a single developmental field defect or as components of several malformation syndromes. The embryogenesis of that defect was studied experimentally by Lash and the developmental relationship between kidneys and limbs has been reviewed by Buchta and Gilbert. The acral anomalies consist of split hand/ split foot, varying combination of oligodactyly, ectrodactyly, syndactyly, brachydactyly, polydactyly or fusion of carpal, tarsal, metatarsal bones of hands and feet. Urinary tract dysplasias are renal agenesis, duplication, ureteral hypoplasia, polycystic kidneys, hydronephrosis and bladder neck obstruction. The authors report three cases of acrorenal syndrome and discuss its clinical and laboratory findings.

Median and Ulnar Nerve Repair Using Sural Nerve Graft: A Case Report

Abstract: Most peripheral nerve injuries (PNI) are caused by trauma. Upper extrimities are most likely to get injured, and the radial nerve is the most common part in upper extrimites to be affected. There are different surgical options available to repair PNI. We reported a 48-years-old male consulted to the Neurosurgery Department for right upper limb weakness and numbness. He had history of laceration due to iron sheeting in the right arm. There was an irregular scar, weakness on right lower arm with hypesthesia, but no neurovascular distal (NVD) abnormalities were found. Further examination showed claw hand. EMG examination revealed total lesion of the right median and ulnar nerve, partial lesion of the right radial nerve with the lesion at wrist level, possibly neurotmesis according to Seddon Classification. Initial debridement, suturing, and repairing of radial artery and flexor carpi ulnar tendon were performed. The patient was then diagnosed as total lesion of the right median and ulnar nerve, partial lesion of the right radial nerve, post repair right ulnar and radial artery and flexor carpi ulnar tendon repair with the planning of nerve graft with no complication under monitoring. The patient was scheduled for sural nerve graft procedure. Early nerve repair or reconstruction is needed even though it only results in incomplete recovery for months to years. The sural nerve is great either in diameter or length which can be a huge source for the grafting of nerve and revealed good outcomes. Recent study showed incomplete recovery especially seen when the patient could not fully clench his hand and his thumb did not move properly during the movement. In conclusion, sural nerve graft is an appropriate choice for peripheral nerve injuries with more benefits included. Prognosis depends on how early the treatment performed and how severe the lesion is. Keywords: median nerve; sural nerve; peripheral nerve injury; nerve repair; nerve grafting

Utility of split hand index with different motor unit number estimation techniques in ALS

ObjectiveUtility of the split hand index (SI) in amyotrophic lateral sclerosis (ALS) has been reported when using the compound muscle action potential (CMAP) amplitude method (SICMAP amp). A motor unit number index (MUNIX) based SI method (SIMUNIX) was purported to exhibit higher sensitivity. The present study assessed the clinical utility of SI, derived by CMAP amplitude, MUNIX and MScan-MUNE (SIMScanFit-MUNE) methods, in ALS. MethodsSixty-two consecutive patients with neuromuscular symptoms (36 ALS and 26 ALS-mimics) were prospectively recruited. The SI was derived by dividing the product of the CMAP amplitude, MUNIX and MScan-MUNE values recorded over first dorsal interosseous and abductor pollicis brevis by values recorded over abductor digit minimi. ResultsSICMAP amp, SIMUNIX and SIMScanFit-MUNE were significantly reduced in ALS, with SICMAP amp (area under curve (AUC) = 0.801) and SIMScanFit-MUNE (AUC = 0.805) exhibiting greater diagnostic utility than SIMUNIX (AUC = 0.713). SICMAP amp and SIMScanFit-MUNE exhibited significant correlations with clinical measures of functional disability and weakness of intrinsic hand muscles. ConclusionsSI differentiated ALS from mimic disorders, with SICMAP amp and SIMScanFit-MUNE exhibiting greater utility. SignificanceThe split hand index represents could serve as a potential diagnostic biomarker in ALS.

Split Hand-Foot and Deafness in a Patient with 7q21.13-q21.3 Deletion Not Including the DLX5/6 Genes.

Split Hand-Foot Malformation (SHFM) is a congenital limb defect characterized by a median cleft of the hands and/or feet due to the absence/hypoplasia of the central rays. It may occur as part of a syndromic condition or as an isolated malformation. The most common of the six genetic loci identified for this condition is correlated to SHFM1 and maps in the 7q21q22 region. SHFM1 is characterized by autosomal dominant transmission, incomplete penetrance and variable expressivity. Associated features often include hearing loss, intellectual disability/developmental delay and craniofacial abnormalities. Disruption of the DLX5/DLX6 genes, mapping within the SHFM1 locus, is now known to be responsible for the phenotype. Through SNP array, we analyzed a patient affected by SHFM1 associated with deafness and an abnormality of the inner ear (incomplete partition type I); we identified a deletion in 7q21, not involving the DLX5/6 genes, but including exons 15 and 17 of DYNC1I1, known to act as exonic enhancers (eExons) of the DLX5/6 genes. We further demonstrated the role of DYNC1I1 eExons in regulating DLX5/6 expression by means of showing a reduced expression of the DLX5/6 genes through RT-PCR in a patient-derived lymphoblastoid cell line. Furthermore, our data and a review of published cases do not support the hypothesis that DLX5/6 are imprinted in humans. This work is an example of how the disruption of regulatory elements can be responsible for congenital malformations.

A complex structural variant near SOX3 causes X-linked split-hand/foot malformation.

Split-hand/foot malformation (SHFM) is a congenital limb defect most typically presenting with median clefts in hands and/or feet, that can occur in a syndromic context as well as in isolated form. SHFM is caused by failure to maintain normal apical ectodermal ridge function during limb development. Although several genes and contiguous gene syndromes are implicated in the monogenic etiology of isolated SHFM, the disorder remains genetically unexplained for many families and associated genetic loci. We describe a family with isolated X-linked SHFM, for which the causative variant could be detected after a diagnostic journey of 20 years. We combined well-established approaches including microarray-based copy number variant analysis and fluorescence in situ hybridization coupled with optical genome mapping and whole genome sequencing. This strategy identified a complex structural variant (SV) comprising a 165-kb gain of 15q26.3 material ([GRCh37/hg19] chr15:99795320-99960362dup) inserted in inverted position at the site of a 38-kb deletion on Xq27.1 ([GRCh37/hg19] chrX:139481061-139518989del). In silico analysis suggested that the SV disrupts the regulatory framework on the X chromosome and may lead to SOX3 misexpression. We hypothesize that SOX3 dysregulation in the developing limb disturbed the fine balance between morphogens required for maintaining AER function, resulting in SHFM in this family.

Cubital Tunnel Syndrome: Does a Consensus Exist for Diagnosis?

Cubital tunnel syndrome (CuTS) is the second most common compressive neuropathy of the upper extremity. We aimed to determine a consensus among experts using the Delphi method for clinical criteria that could be validated further for the diagnosis of CuTS. The Delphi method was used for establishing a consensus among a group of expert panelists, comprising 12 hand and upper-extremity surgeons, who ranked the diagnostic clinical importance of 55 items related to CuTS on a scale from 1 (least important) to 10 (most important). The average and SDs of each item were calculated, and Cronbach α was used to assess homogeneity among the panelist-ranked items. All panelists answered the 55-item questionnaire. A Cronbach α value of 0.963 was obtained on the first iteration. The top criteria that were considered most clinically relevant to the diagnosis of CuTS among the group were determined based on the most highly ranked and correlated items among the expert panelist group. The criteria based on which there was agreement were as follows: (1) paresthesias in ulnar nerve distribution, (2) symptoms precipitated by increased elbow flexion/positive elbow flexion tests, (3) positive Tinel sign at the medial elbow, (4) atrophy/weakness/ late findings (eg, claw hand of the ring/small finger and Wartenberg or Froment sign) of ulnar nerve-innervated muscles of the hand, (5) loss of two-point discrimination in ulnar nerve distribution, and (6) similar symptoms on the involved side after successful treatment on the contralateral side. Our study demonstrated a consensus among an expert panelist group of hand and upper-extremity surgeons on potential diagnostic criteria for CuTS. This consensus on diagnostic criteria may help clinicians readily diagnose CuTS in a standardized form; however, further weighting and validation are necessary prior to the development of a formal diagnostic scale. This study is the first step in producing a consensus on how to diagnose CuTS.

Abductor Pollicis Brevis/Abductor Digiti Minimi Compound Muscle Action Potential Ratio as a Diagnostic Marker for Amyotrophic Lateral Sclerosis

Background: We aimed to assess the diagnostic utility of abductor pollicis brevis/abductor digiti minimi compound muscle action potentials (APB/ADM CMAP) ratio as an indicator of split hand phenomenon in the differentiation of amyotrophic lateral sclerosis (ALS) patients from healthy controls. Objectives: To assess diagnostic utility of APB/ADM CMAP ratio as an indicator split hand phenomenon in differentiation of ALS patients from healthy controls. Materials & Methods: This cross-sectional retrospective study was conducted at Alzahra and Kashani hospitals of Isfahan, Iran, in 2021. The study population consisted of all patients with definite diagnoses of ALS who had undergone electrophysiological studies within the previous 5 years. APB/ADM CMAP ratio was calculated in both groups based on right/left hand and below/ over 50 years of age. The statistical analysis also evaluated the diagnostic accuracy of the APB/ ADM amplitude ratio. Results: A total of 200 ALS patients and 200 healthy controls were evaluated. APB/ADM ratios of the right hand in the controls and patients were 1.27±0.71 and 1.27±1.69 (P=0.961), while in the left hand, these figures were 1.30±0.54 and 1.11±0.97, respectively (P=0.018). Analysis based on age group revealed a significant difference in the APB/ADM amplitude ratio in the left hand of individuals younger than 50. The cut-off points of 0.81 (sensitivity=86.2% and specificity=58.7%) and 1.03 (sensitivity=72.5% and specificity=58.5%) were calculated for right and left hands, respectively. Conclusion: APB/ADM CMAP ratio is a relatively highly sensitive but moderately specific diagnostic marker for differentiating ALS patients from healthy controls with higher diagnostic utility in patients younger than 50.

Sequence Variants in the WNT10B Underlying Non-Syndromic Split-Hand/Foot Malformation

Introduction: Split hand and foot malformation (SHFM) or ectrodactyly is a rare limb deformity characterized by median cleft of the hand and foot with impaired or missing central rays. It can occur as an isolated anomaly or in association with abnormalities of other body parts. Methods: After delineating the clinical features of two families (A–B), with non-syndromic SHFM, exome and Sanger sequencing were employed to search for the disease-causing variants. Results: Analysis of exome and Sanger sequencing data revealed two causative variants in the WNT10B gene in affected members of the two families. This included a novel missense change [c.338G>C; p.(Gly113Ala)] in family A and a previously reported frameshift variant [c.884-896delTCCAGCCCCGTCT; p.(Phe295Cysfs*87)] in family B. Conclusion: Our findings add a novel variant in WNT10B gene as the underlying cause of SHFM. The finding adds to the growing body of knowledge about the genetic basis of developmental disorders and provides valuable insights into the molecular mechanisms that regulate limb development.

Cervical Spine Magnetic Resonance Imaging Findings in Hirayama Disease.

Background Hirayama disease is an uncommon type of cervical cord myelopathy seen typically in young males due to trauma from flexion movements. This study aims to assess the clinical presentations and classify the extent of various cervical spine MRI findings for the local population. Methodology A retrospective study of 13 patients diagnosed with Hirayama disease oncervical MRI was performed from January 2017 to December 2022 at Dr. D. Y. Patil Medical College, Hospital and Research Center, Pune. Results Of the 13 patients, 12 (92%) were male, and one (8%) was female. Nine (69%) patients were in the 16-25-year age group, two (15%) were in the 26-35-year age group, and one (8%) each was in the 6-15-year and 66-75-year age groups. Upper limb weakness was the most common clinical symptom seen in 12 (92%) patients, followed by distal muscle atrophy in seven (54%) patients. Tremors in the hand were a rare symptom seen in two patients. Claw hand was an atypical symptom seen in one patient. On cervical MRI, all patients showed excessive forward shifting of the posterior dura on flexion, with resultant cord compression due to tightness of the dural sac. One (8%) patient had no signs of myelopathy, while 12 (92%) patients had developed chronic myelomalacia and showed abnormal cord hyperintensity and atrophy in the lower cervical cord. All 13 (100%) patients showed increased laminodural space on flexion; the mean thickness was 4.08 mm, with the minimum and maximum thickness being 2.4 mm and 6.7 mm, respectively. Classifying by length of the anterior bulging dura, one (8%) patient showed involvement of less than two vertebral body segments, eight (62%) patients showed involvement of two to four vertebral body segments, and four (30%) patients showed involvement of more than four vertebral body segments. Crescent-shaped post-contrast enhancement on flexion was seen in all eight (100%) patients who underwent a contrast study. Prominent epidural flow voids on flexion were seen in six (46%) patients. Conclusions Hirayama disease is an uncommon type of cervical myelopathy seen typically in juvenile males. The occult onset of distal upper limb weakness and atrophy during puberty, typical MRI features of lower cervical cord atrophy, and the presence of a crescent-shaped enhancing mass in the posterior epidural space are pathognomonic of the condition. A few atypical cases can also occur. Early diagnosis and treatment are crucial to avoiding serious dysfunction.

A novel frameshift variant in UBA2 causing split-hand/foot malformations in a Pakistani family

Split-hand/foot malformation (SHFM) shows diverse heterogeneity and manifests with reduced penetrance and variable expressivity. This study investigated the underlying genetic cause of a family segregating SHFM. Exome sequencing followed by Sanger sequencing identified a novel single nucleotide heterozygous variant (NC_000019.9 (NM_005499.3):c.1118del) in UBA2 cosegregating in the family in an autosomal dominant manner. Our findings conclude that reduced penetrance and variable expressivity are the two remarkable and unusual features of SHFM.

Exploring the split hand phenomenon with the neurophysiological index

In 164 subjects of different age groups, we studied the neurophysiological index (NI) ([CMAP amplitude/Distal motor latency] *[F-wave frequency]; CMAP=compound muscle action potential) for three hand muscles (APB= abductor pollicis brevis; FDI= first dorsal interosseous; ADM= abductor digiti minimi). A split hand index based on CMAP amplitude (SHI_CMAP) and NI (SHI_NI) were calculated ([APB CMAP amplitude or NI * FDI CMAP amplitude or NI]/[ADM CMAP amplitude or NI]). All these neurophysiological measurements differed between age groups (p<0.001). Hand muscle NIs, as well as SHI_NI and SHI_CMAP were age dependent. This may be relevant for diagnostic purposes in motor neuron diseases.

New cases of childhood leprosy in two male siblings in low endemic province: an iceberg phenomenon?

Children are the leprosy population most at risk; multibacillary infections are common. We reported pediatric cases with WHO-multibacillary lepromatous type morbus Hansen. We discovered several hypopigmented patches on the right upper arm, anesthesia-filled claw hands, and infiltrates in the ears in one 17- year-old child. In the other case (13-year-old), we discovered reduced sensory sensitivity in nearly every area of the body, infiltrates on the ear, and numerous irregular hypopigmented plaques on the belly, lumbar, and gluteus. Both patients had positive acidfast bacteria. After three months of treatment, multibacillary leprosy patients began to show improvement. Low socioeconomic and environmental conditions, as well as a history of intimate contact with leprosy patients, have been identified as risk factors.

N°199 – Reverse split hand sign in Spinal Muscular Atrophy and Hirayama disease: A comparative clinico-electrophysiological study

N°199 – Reverse split hand sign in Spinal Muscular Atrophy and Hirayama disease: A comparative clinico-electrophysiological study

Characteristic and management motor neuron disease in the largest tertiary hospital in the Philippines: A one-year period cross sectional analytic study

BackgroundMotor neuron disease (MND) is largely understudied in many underdeveloped and developing countries, including the Philippines. The practice and management of MND is generally insufficient, and thus, the quality of life of these patients are consequently compromised. ObjectivesThe aim of this study is to determine the clinical profile and describe the management of MND patients seen in the largest tertiary hospital in the Philippines for one year. MethodsThis is a cross-sectional study of MND patients diagnosed clinically and via electromyogram-nerve conduction study (EMG NCS) in the Philippine General Hospital (PGH) from January to December 2022. Clinical characteristics, diagnostics and management information were obtained and summarized. ResultsThe incidence of MND in our neurophysiology unit was 4.3% (28/648), with amyotrophic lateral sclerosis (ALS) being the most common variant (67.9%, n = 19). Male to Female ratio was 1:1, with the median age of onset of 55 (36–72) years old and median onset duration to diagnosis of 1.5 (0.25–8) years. Limb onset was more prevalent (82.14%, n = 23) with upper limbs initially involved (79.1%, n = 18). Split hand syndrome was found in almost half (53.6%) of the patients. The median ALS functional rating score-revised (ALSFRS-R) and medical research council (MRC) scores were 34 (8–47) and 42(16–60) respectively while the median King’s clinical stage was 3 (1–4). Only half of the patients were able to undergo magnetic resonance imaging (MRI) and only one had neuromuscular ultrasound. Only one of the 28 patients was able to take riluzole, and only one was on oxygen support. None had gastrostomy and none used non-invasive ventilation. ConclusionThis study showed that the management of MND in the Philippines is largely inadequate and further improvement in the health care system in handling rare neurologic cases must be implemented to enhance their quality of life.

Distal Nerve Exploration in the Palm Avoids Nerve Transfer in a Posttraumatic Ulnar Nerve Injury with a Claw Hand

AbstractPosttraumatic low ulnar nerve injuries develop claw hand and poor hand function. Transferring the opponens pollicis branch of the thenar branch at the palm to the terminal division of the deep branch of the ulnar nerve is an effective distal nerve transfer to restore pinch in low ulnar nerve injuries. The author describes the surgical technique for a 4-month-old low ulnar nerve injury in a 25-year-old man with inconclusive electrodiagnostic findings and no clinical findings of distal nerve recovery. The intraoperative electrical stimulation of the nerve in the palm is a simple method to ensure the reinnervation of the ulnar nerve in a claw hand and muscle wasting. Therefore, all postcut injuries with a low ulnar nerve palsy with claw hands may not need a distal nerve transfer. However, performing distal nerve exploration in the palm is vital in cases of doubtful nerve recovery in a low ulnar nerve palsy with a claw hand.

PRDM1 DNA-binding zinc finger domain is required for normal limb development and is disrupted in split hand/foot malformation.

Split hand/foot malformation (SHFM) is a rare limb abnormality with clefting of the fingers and/or toes. For many individuals, the genetic etiology is unknown. Through whole-exome and targeted sequencing, we detected three novel variants in a gene encoding a transcription factor, PRDM1, that arose de novo in families with SHFM or segregated with the phenotype. PRDM1 is required for limb development; however, its role is not well understood and it is unclear how the PRDM1 variants affect protein function. Using transient and stable overexpression rescue experiments in zebrafish, we show that the variants disrupt the proline/serine-rich and DNA-binding zinc finger domains, resulting in a dominant-negative effect. Through gene expression assays, RNA sequencing, and CUT&RUN in isolated pectoral fin cells, we demonstrate that Prdm1a directly binds to and regulates genes required for fin induction, outgrowth and anterior/posterior patterning, such as fgfr1a, dlx5a, dlx6a and smo. Taken together, these results improve our understanding of the role of PRDM1 in the limb gene regulatory network and identified novel PRDM1 variants that link to SHFM in humans.

Inducing Ulnar Nerve Function while Eliminating Claw Hand and Reducing Chronic Neuropathic Pain

Ulnar nerve injury induces chronic neuropathic pain and is frequently devastating due to loss of cupping the hand around objects (finger clawing) and diminished grip strength. There is little chance of restoring good function, eliminating finger clawing, or reducing the pain. A novel technique was tested for its efficacy in promoting ulnar nerve function and reducing finger clawing and chronic neuropathic pain. A 25-year-old subject presented 5.7 months after a wrist gunshot that created three nerve gaps proximal to the deep ulnar nerve branch. He sought restoration of function due to developing ulnar nerve injury-induced claw hand and increasingly severe chronic neuropathic pain. After resection of the scarred nerve tissue, each gap was 10 cm long. The gaps were bridged with two nonreversed sural nerve grafts within a PRP-filled NeuroMend collagen tube (Collagen Matrix, Oakland, N.J.). Some axons regenerated entirely across all three 10-cm-long repaired nerve gaps, restoring excellent topographically correct sensitivity of S4, including two-point discrimination of 4 mm, good M4 motor function, and full ROM. The ulnar nerve injury-induced finger clawing was eliminated, and the chronic neuropathic pain of 7 was reduced to 0 on a 0-10 validated scale and did not return over the following 3.75 years. Thus, this novel technique induces good sensory and motor function, despite repairing three 10-cm-long nerve gaps while eliminating ulnar nerve injury-induced hand clawing and chronic neuropathic pain. Further studies are required to determine whether the effects were due to PRP.

Congenital hand anomalies and rare syndromes in children

Congenital hand anomalies and associated rare syndromes in children are commonly seen in clinical practice and require complete clinical, radiological and genetic evaluation. The purpose of this case series is to describe four rare syndromic children with varied hand anomalies and differences. Three of the children are female and one is a male. Distal limb defects from simple polydactyly, clinodactyly to cleft hand were identified including preaxial anomalies. Significant clinical problems noted were chiefly cosmetic and altered self-image was also noted in one child. The orofacial clefting noted in the child with ectrodactyly ectodermal dysplasia (EEC) syndrome required repeated surgery though the child had minimal feeding difficulty and significant speech delay. Multidisciplinary management is necessary with the early involvement of clinical geneticist.