Finger Anomalies Research Articles

Pathogenic Copy Number Variations Involved in the Genetic Etiology of Syndromic and Non-Syndromic Intellectual Disability-Data from a Romanian Cohort.

The investigation of unexplained global developmental delay (GDD)/intellectual disability (ID) is challenging. In low resource settings, patients may not follow a standardized diagnostic process that makes use of the benefits of advanced technologies. Our study aims to explore the contribution of chromosome microarray analysis (CMA) in identifying the genetic etiology of GDD/ID. A total of 371 Romanian patients with syndromic or non-syndromic GDD/ID, without epilepsy, were routinely evaluated in tertiary clinics. A total of 234 males (63.07%) and 137 (36.93%) females, with ages ranging from 6 months to 40 years (median age of 5.5 years), were referred for genetic diagnosis between 2015 and 2022; testing options included CMA and/or karyotyping. Agilent Technologies and Oxford Gene Technology CMA workflows were used. Pathogenic/likely pathogenic copy number variations (pCNVs) were identified in 79 patients (21.29%). Diagnosis yield was comparable between mild ID (17.05%, 22/129) and moderate/severe ID 23.55% (57/242). Higher rates were found in cases where facial dysmorphism (22.97%, 71/309), autism spectrum disorder (ASD) (19.11%, 26/136) and finger anomalies (20%, 27/96) were associated with GDD/ID. GDD/ID plus multiple congenital anomalies (MCA) account for the highest detection rates at 27.42% (17/62). pCNVs represent a significant proportion of the genetic causes of GDD/ID. Our study confirms the utility of CMA in assessing GDD/ID with an uncertain etiology, especially in patients with associated comorbidities.

A chromoanagenesis-driven ultra-complex t(5;7;21)dn truncates neurodevelopmental genes in a disabled boy as revealed by whole-genome sequencing

Germline or constitutional chromoanagenesis-related complex chromosomal rearrangements (CCRs) are rare, apparently “all-at-once”, catastrophic events that occur in a single cell cycle, exhibit an unexpected complexity, and sometimes correlate with a severe abnormal phenotype. The term chromoanagenesis encompasses three distinct phenomena, namely chromothripsis, chromoanasynthesis, and chromoplexy. Herein, we found hallmarks of chromothripsis and chromoplexy in an ultra-complex t(5;7;21)dn involving several disordered breakpoint junctions (BPJs) accompanied by some microdeletions and the disruption of neurodevelopmental genes in a patient with a phenotype resembling autosomal dominant MRD44 (OMIM 617061). G-banded chromosomes and FISH showed that the CCR implied the translocation of the 5p15.2→pter segment onto 7q11.23; in turn, the fragment 7q11.23→qter of der(7) separated into two pieces: the segment q11.23→q32 translocated onto 5p15.2 and fused to 21q22.1→ter in the der(5) while the distal 7q32→qter segment translocated onto der(21) at q22.1. Subsequent whole-genome sequencing unveiled that CCT5, CMBL, RETREG1, MYO10, and TRIO from der(5), IMMP2L, TES, VPS37D, DUS4L, TYW1B, and FEZF1-AS1 from der(7), and TIAM1 and SOD1 from der(21), were disrupted by BPJs, whereas some other genes (predicted to be haplosufficient or inconsequential) were completely deleted. Although remarkably CCT5, TRIO, TES, MYO10, and TIAM1 (and even VPS37D) cooperate in key biological processes for normal neuronal development such as cell adhesion, migration, growth, and/or cytoskeleton formation, the disruption of TRIO most likely caused the patient's MRD44-like phenotype, including intellectual disability, microcephaly, finger anomalies, and facial dysmorphia. Our observation represents the first truncation of TRIO related to a chromoanagenesis event and therefore expands the mutational spectrum of this crucial gene. Moreover, our findings indicate that more than one mechanism is involved in modeling the architecture of ultra-complex rearrangements.

Accuracy of predictive equations in guiding tracheal intubation depth in children: A prospective study.

Accurate insertion depth of endotracheal tube (ETT) in children has been predicted using the demographic variables, such as age, weight, and height. Middle finger length showed good correlation with ETT depth measurement in children aged 4-14years. The primary objective was to correlate the actual ETT insertion depth with the depth derived from middle finger length, age, weight, and height formulae in children aged 1-4years. The secondary objective was to find the most accurate formula for prediction of ETT insertion depth. This prospective parallel group study was done in 50 american society of anesthesiologists 1 or 2 children aged 1-4years undergoing elective surgery under general anesthesia. Children with difficult airway, finger anomalies, or syndromic associations were excluded. Age, weight, height, and middle finger length of all children were measured. Depth of orally inserted uncuffed ETT and tracheal length was measured by fiberoptic bronchoscopy. The actual ETT depth was correlated with the depth calculated from different formulae. The mean middle finger length was 4.42±0.50cm, age was 2.64±1.07years, weight was 12.28±2.84kg, and height was 82.89±16.23cm. The mean tracheal length was 6.42±0.96cm. The mean depth of ETT was actual depth (12.89±1.09cm), middle finger depth (13.23±1.53cm; p=.001; 95%CI 0.12-0.50), age-based depth 1(3.31±0.53cm; 95%CI 0.37-1.44; p=.001), weight-based depth (14.14±1.42cm; 95% CI 0.10-0.51; p=.004), and height-based depth (13.73±0.94cm; 95% CI 0.15-0.77; p=.004). Middle finger length and age-based formulae showed higher number of accurate placements (58% each). Weight- (74%) and height (64%)-derived formulae gave a higher number of distal ETT placements. Formulas based on the demographic variables and middle finger length showed good correlation with the actual ETT depth in children aged 1-4years. The percentage of accurate ETT depth placements was higher with middle finger length and age-based formulae.

Postoperative Bronchospasm in a Child with Coffin-Siris Syndrome Following Administration of Sugammadex

A 13-year-old boy with Coffin-Siris syndrome was scheduled to undergo dental surgery for dental treatment with general anesthesia. Mental retardation, finger anomalies and coarse facies features were recorded in preoperative assessment. Propofol, Fentanyl and Rocuronium were given for anesthesia induction. Sevoflurane was used as an inhalation anesthetic drug in anesthesia maintenance.

Alveolar capillary dysplasia without misalignment of pulmonary veins, hyperinflammation, megalocornea and overgrowth – Association with a homozygous 2bp-insertion in LTBP2?

We present a male infant with alveolar capillary dysplasia without misalignment of pulmonary veins, hyperinflammation, megalocornea and macrosomia/macrocephaly at birth. Whole-exome sequencing revealed a homozygous 2bp-insertion in the latent transforming growth factor-beta binding protein 2 (LTBP2) (c.278_279dup, p.(Ser94Glyfs*187)). So far, LTBP2-variants have been frequently reported with an eye-restricted phenotype including primary congenital glaucoma and megalocornea/microspherphakia and ectopia lentis with/without secondary glaucoma. Hitherto reported systemic phenotypes showed, among others, features as tall stature, finger anomalies, high-arched palate and cardiovascular anomalies. The main pathophysiological finding of our patient was an alveolar capillary dysplasia (with pulmonary arterial hypertension and right ventricular impairment but without misalignment of pulmonary veins) resulting in almost continuous oxygen demand and prolonged dependence on mechanical ventilation. He died of respiratory failure at the age of seven months. This patient may extend the LTBP2-related phenotype with resulting diagnostic implications.

Upper limb congenital muscular hypertrophy and aberrant muscle syndrome in children.

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'Epidemic' of hand deformities in the French Renaissance paintings of Jean and François Clouet.

This article analyses the nature of the multiple finger anomalies found in portraits by the French Renaissance artistic dynasty, the Clouets. The multiplicity of finger anomalies could be either innocent congenital variants, or pathological and traumatic deformities. In view of the presence of such `beautifying variations' in the works of other Renaissance artists, the authors decided that these features were not the result of an epidemic of deformities, but instead represented a stylistic approach in paintings of this period at the French Court.

Moebius syndrome with macular hyperpigmentation, skeletal anomalies, and hypoplasia of pectoralis major muscle in an Egyptian child

We report a 4month old female infant, 3rd in order of birth of the first cousin consanguineous parents. The patient has congenital right facial nerve palsy, with asymmetry of facial expression during crying and difficulty in swallowing. Associated anomalies include abnormal facial features, bilateral finger anomalies, bilateral talipes equinovarus, kyphoscoliosis, hypotonia, high frequency hearing loss. Bilateral macular hyperpigmentation was detected in our patient on fundus examination which was not reported previously in Moebius syndrome cases. In addition there is hypoplasia of the right pectoralis major muscle.

Medical tactic in hand polydactyly in children

Untimely correction of anomalies of fingers and hands or inefficiently performed reconstructive operations may affect the processes of adaptation of children to life. Objective: To improve outcomes in children with polydactyly by optimizing the methods of surgical correction of congenital hand pathology. Methods: During the period from 2000 to 2012 in 118 patients (70 boys, 48 girls, age to 6 years) with polydactyly there were performed 141 operations on 136 hands. There were 68 children with radial form of polydactyly, 17 with ulnar form, and 3 with central one. For establishment of the nature of the pathology examination with using of radiological, CT, and ultrasound dopplerography mapping was done. Results: In the case of the main finger deformity after removal of additional finger we performed corrective osteotomies, modeling resections of articular surfaces, and restored capsular-ligamentous apparatus. In cases of ulnar polydactyly with thickening of V metacarpal bone on the wide head of which there are two claw like little fingers we removed less developed one, cut off the abductor digiti minimi, restored lateral metacarpophalangeal ligament, fixed the muscle to the proximal phalanx, angular deformity of the V finger we eliminated by wedge osteotomy with K-wire fixation. In cases of central polydactyly after removal of extra finger we used created from a remote segment reserve of skin for closing the skin defect on lateral surfaces of the fingers with simultaneous correction of axial deformities. Long-term outcomes were followed up during the period of 1 to 10 years in 78 children: good results were obtained in 44 cases, satisfactory — in 27, and unsatisfactory — in 7 cases. Errors and complications: deviation of the main finger, nonunion of bone surfaces, scar deformities, limitation of movement. Conclusions: While choosing the method of surgery and duration of its execution one should establish the primary and the secondary fingers in cases of radial polydactyly. Zigzag incisions, rational skin, bone and tendon plasty allow to prevent the formation of scar contractures and secondary deformities of fingers and contribute to the restoration of the hand function.

Nasoalveolar Molding Treatment for a Patient With Amniotic Band Syndrome: A Case Report

ABSTRACT Amniotic band syndrome (ABS) is an uncommon congenital malformation characterized by clubfoot deformity, hand and finger anomalies, and cleft lip and palate. In this study, the literature about ABS—possible etiology, treatment protocols, and medical procedures—is discussed. The aim of this study was to evaluate efficiency of nasoalveolar molding therapy for a patient with cleft lip and palate and ABS. Changes were evaluated before, during, and after the treatment period using a three-dimensional surface imaging system.

A familial case with brachydactyly type C with a GDF5 mutation

A 54-year-old Korean man visited the genetics clinic because of bilateral finger anomalies. On both his hands, the second and third fingers were short, with ulnar deviation. The first, fourth, and fifth fingers were normal, and the fourth finger was the longest. The range of motion was normal in all the fingers. Otherwise, his upper and lower arms, lower extremities, and feet were normal. No facial dysmorphism was observed. Intellectual performance was normal. Neither of his parents were affected. He had two sons, one of whom had shortened the second and A familial case with brachydactyly type C with a GDF5 mutation

Fluid ascent during the 2004–2005 unrest at Mt. Spurr inferred from seismic tomography

We present a seismic model of the crust beneath Mt. Spurr Volcano in Alaska based on tomographic inversion of local earthquake data recorded by temporary seismic network during the unrest of Mt. Spurr in 2004–2005. Beneath the northern vent of Mt. Spurr, where the most intensive fumarolic activity was observed during the last unrest, we observe a finger‐shaped anomaly with a higher P and lower S velocity, which corresponds to high Vp/Vs ratio. Another anomaly is located to the south of Crater Peak approximately beneath the same location where an explosive eruption occurred in 1992. We propose that these two finger anomalies represent separated conduits of magma and volatiles. The NE conduit extends to the surface and enables free volatile flux. The SE conduit seems to be blocked at a ca. 20 km depth and in case of continuous pressure build up may become a source of an explosive eruption.

CASK aberrations in male patients with Ohtahara syndrome and cerebellar hypoplasia

Ohtahara syndrome (OS) is one of the most severe and earliest forms of epilepsy. STXBP1 and ARX mutations have been reported in patients with OS. In this study, we aimed to identify new genes involved in OS by copy number analysis and whole exome sequencing. Copy number analysis and whole exome sequencing were performed in 34 and 12 patients with OS, respectively. Fluorescence in situ hybridization, quantitative polymerase chain reaction (PCR), and breakpoint-specific and reverse-transcriptase PCR analyses were performed to characterize a deletion. Immunoblotting using lymphoblastoid cells was done to examine expression of CASK protein. Genomic microarray analysis revealed a 111-kb deletion involving exon 2 of CASK at Xp11.4 in a male patient. The deletion was inherited from his mother, who was somatic mosaic for the deletion. Sequencing of the mutant transcript expressed in lymphoblastoid cell lines derived from the patient confirmed the deletion of exon 2 in the mutant transcript with a premature stop codon. Whole exome sequencing identified another male patient who was harboring a c.1A>G mutation in CASK, which occurred de novo. Both patients showed severe cerebellar hypoplasia along with other congenital anomalies such as micrognathia, a high arched palate, and finger anomalies. No CASK protein was detected by immunoblotting in lymphoblastoid cells derived from two patients. The detected mutations are highly likely to cause the loss of function of the CASK protein in male individuals. CASK mutations have been reported in patients with intellectual disability with microcephaly and pontocerebellar hypoplasia or congenital nystagmus, and those with FG syndrome. Our data expand the clinical spectrum of CASK mutations to include OS with cerebellar hypoplasia and congenital anomalies at the most severe end.

4q34.1–q35.2 deletion in a boy with phenotype resembling 22q11.2 deletion syndrome

Small terminal or interstitial deletions involving bands 4q34 and 4q35 have been described in several patients with a relatively mild phenotype such as mild to moderate intellectual disability and minor dysmorphic features. We present a boy born from unrelated parents with a de novo 4q34.1-q35.2 deletion and clinical features resembling 22q11.2 deletion syndrome. To the best of our knowledge, this is the first reported patient with 4q34-q35 deletion and phenotype resembling 22q11.2 deletion syndrome without fifth finger anomalies as a specific feature of 4q- syndrome. G-banding karyotyping disclosed the deletion, which was further delineated by microarray comparative genomic hybridization. Fluorescence in situ hybridization and multiplex ligation-dependent probe amplification analyses did not reveal rearrangements of 22q11.2 region. MLPA confirmed the deletion within the 4q35.2 region. Given the considerable clinical overlaps between the 22q11.2 deletion syndrome and clinical manifestation of the patient described in this study, we propose that region 4q34.1-q35.2 should be considered as another region associated with phenotype resembling 22q11.2 deletion syndrome. We also propose that distal 4q deletions should be considered in the evaluation of patients with phenotypic manifestations resembling 22q11.2 deletion syndrome in whom no 22q11.2 microdeletion was detected, even in the absence of distinctive fifth finger anomalies. Additionally, we underline the importance of applying array CGH that enables simultaneous genome-wide detection and delineation of copy number changes (e.g., deletions and duplications).

Duplication at chromosome 2q31.1-q31.2 in a family presenting syndactyly and nystagmus

HOXD genes encode transcription factors involved in the antero-posterior patterning of the limb bud and in the specification of fingers. During the embryo development, HOXD genes are expressed, following a spatio-temporal colinearity that involves at least three regions, centrometric and telomeric to this cluster. Here, we describe a father and a daughter presenting a 3-4 hand bilateral syndactyly associated with a nystagmus. Array-comparative genomic hybridisation showed a 3.8 Mb duplication at 2q31.1-q31.2, comprising 27 genes including the entire HOXD cluster. We performed expression studies in lymphoblasts by reverse transcription-PCR and observed an HOXD13 and HOXD10 overexpression, whereas the HOXD12 expression was decreased. HOXD13 and HOXD10 overexpression, associated with a misregulation of at least HOXD12, may therefore induce the syndactyly. Deletions of the HOXD cluster and its regulatory sequences induce hand malformations and, particularly, finger anomalies. Recently, smaller duplications of the same region have been reported in association with a mesomelic dysplasia, type Kantaputra. We discuss the variable phenotypes associated with such 2q duplications.

The face of Ulnar Mammary syndrome?

Ulnar Mammary syndrome (UMS) is an autosomal disorder caused by haploinsufficiency of the TBX3 gene. There is marked intrafamilial variation in expression of the syndrome. We present one three generation family in which the proband has absence of the right ulna and third, fourth and fifth rays in her right hand. Her mother and maternal grandmother have more subtle anomalies while all have a similar facial appearance with a broad nasal tip, a broad jaw, a prominent chin and a tongue frenulum. They have a single base pair insertion (c. 992dup) in TBX3. We compare faces from the handful of published UMS patients which include photographs, this family and four other cases with TBX3 mutations. All have similarities in appearance which we suggest could alert clinicians to the possibility of a TBX3 mutation if individuals present with more subtle features of UMS such as postaxial polydactyly, isolated 5th finger anomalies, delayed puberty in males, breast hypoplasia or short stature with or without growth hormone deficiency.

Amniotic band disruption sequence

A disruption of limb vasculature after the period of embryonic development can result in structural anomalies. This disruption can be due to tangled strands of amnion that encircle embryonic structures, placental emboli or death of a monozygotic twin [1]. Up to 50% of cases have other congenital anomalies including cleft lip, cleft palate, and clubfoot deformity [2]. Hand and finger anomalies occur in up to 80%. Other abnormalities found with amniotic band syndrome include clubhands, cleft lip and/or cleft palate, and haemangioma. The incidence varies from 1 in 10000 to 1 in 15000 live births.

Congenital ocular motor apraxia: Clinical and neuroradiological findings, and long-term intellectual prognosis

The severity of intellectual sequelae and prognosis varies in patients with congenital ocular motor apraxia (COMA). Here, we explored this phenomenon with regard to the accompanying oculomotor signs and gross motor development, as well as the subtentorial structure defects. Ten patients diagnosed with COMA (M:F = 4:6, 4–37 years old) were reviewed. Four individuals who gained the ability to walk at 2 years or earlier showed normal intellect and social skills. Those who walked later often showed accompanying intellectual (5/6) and speech (6/6) disabilities. In this latter group, atypical oculomotor signs for COMA (presence of nystagmus, mild limitation of vertical gaze, slower head thrust, and marked improvement of lateral saccade during early childhood) were often noted (4/6). Minor anomalies of fingers and toes were also common in this group. Neuroimaging was conduced in nine patients (pneumoencepharography 1; computed tomography: 8, magnetic resonance imaging: 2). Dilatation of the fourth ventricle, mainly at the level of the midbrain or upper pons ( n = 7), and hypoplastic cerebellar vermis ( n = 6) were commonly observed in both the early- and late-walking groups. ‘Molar tooth’ signs ( n = 3) were exclusively noted in the late-walking group, and often accompanied by atypical oculomotor signs (3/3) and intellectual disabilities (2/3). Vermian hypoplasia and dilatation of the fourth ventricle at the upper brainstem level in COMA patients, with or without intellectual disabilities, suggested that the cardinal lesion for OMA may exist in these areas. The presence of a subset of ‘atypical’ COMA patients may suggest that COMA with subtle infratentorial abnormality represents a heterogeneous disease category, showing similar oculomotor disturbance. This review indicated that clinical and neuroradiological inspection might be valuable for prediction of long-term intellectual prognosis in COMA patients.

Cytogenetic analysis of partial trisomy 9p resulting from a reciprocal balanced 9/21 translocation

In this study, a four-generation Chinese family in Nanyang, Henan Province was identified with partial trisomy 9p syndrome. Of the 23 family members studied, six were characterized with mental retardation and mild facial and little finger anomalies. All affected family members demonstrated significant intrafamilial homogeneous phenotype except concomitance epilepsy in proband. On the basis of G-banding, the proband showed a translocation between chromosomes of 9p and 21q and partial 9p trisomy. The karyotype was 46, XY, der (21) t (9; 21) (9p22.2; 21q22.3) pat. Further karyotyping of other affected members and their patients in this family revealed translocation of chromosomes of 9p and 21q, with partial 9p trisomy in all affected members. The partial 9p trisomy was the direct result of abnormal segregation of a balanced translocation cell between chromosome 9 and 21 in one of the parents. The extra distal half of the short arm of chromosome, 9pter-->9p21, is responsible for the major clinical features such as mental retardation and mild facial anomaly. The cause of epilepsy in proband was discussed.

Breakpoints around the HOXD cluster result in various limb malformations

Background: Characterisation of disease associated balanced chromosome rearrangements is a promising starting point in the search for candidate genes and regulatory elements. Methods: We have identified and investigated three patients...