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Gollop-Wolfgang complex is defined as the presence of a distal bifid femur and tibial hemimelia with or without hand ectrodactyly. The condition commonly presents with several skeletal abnormalities and internal organ congenital defects. We hereby report a case with a classical presentation of Gollop-Wolfgang complex.

Background Digital transfer for hand reconstruction in children with cleft hand and foot differences present unique challenges with anomalous anatomy and rare opportunities to dramatically improve function of one- or two-digit hands. Methods Medical records were reviewed for patients with cleft hand and foot treated at two pediatric institutions between 1996 and 2018. Hospital records, clinical photographs, radiographs, and alginate molds were available on all patients. Patient characteristics, indications for transfer, associated syndromes, donor and recipient anatomy, and complications were examined. Results Twenty digital transfers were identified in 16 patients. The mean age at time of transfer was 6 years (range: 3–18 years). Associated syndromes in this study included ectrodactyly ectodermal dysplasia clefting (EEC) syndrome and Goltz's syndrome. Recipient sites included the thumb (n = 17) and index ray (n = 3) in 10 hands with monodactyly, 6 hands with a two-digit ulnar syndactyly, and 3 hands with central deficiency and associated polydactyly or other anomalies. Donor sites included the great toe (n = 7), fifth toe (n = 9), great toe polydactyly (n = 2), thumb polydactyly (n = 1), and second toe (n = 1). All transfers survived. Revisions included tenolysis (n = 2), repeat fixation for nonunion or malunion (n = 2), and fusion for instability (n = 3). Conclusion Digital transfer in cleft hand and foot patients is a functional endeavor. The transferred digits provide sensation, mobility, and stability for opposition. Technically challenging due to small structures and atypical anatomy, these rare cases represent unique opportunities to improve function and appearance in the pediatric hand. This is a therapeutic study and reflects level of evidence IV.

We present the case of a male who shortly after birth developed acute respiratory distress due to bilateral choanal atresia, following which he was found to have rectal stenosis. Genetic testing for CHARGE syndrome was negative, but whole genome sequencing identified heterozygosity for a pathogenic missense variant in TP63 (c.727C > T, p.(Arg243Trp). He also has partial cutaneous syndactyly of the third and fourth fingers of the right hand, and bilateral lacrimal duct stenosis/aplasia. A later maxillofacial review identified a palpable submucousal cleft and his scalp hair is blond and slightly sparse. Choanal atresia and rectal stenosis are recognized features of ectrodactyly-ectodermal dysplasia-clefting syndrome, but we believe this is the first report of a case presenting with these features in the absence of the cardinal features.

Ectrodactyly-ectodermal dysplasia clefting syndrome is a rare genetic disorder characterized by the triad of ectrodactyly-ectodermal dysplasia and facial clefting of lip or palate or both along with some systemic manifestations. Although each defect that comprises the syndrome has been known to occur as a separate entity, the congregation of all three anomalies in a single individual appears to be an extremely rare occurrence, with incidence being approximately 1.5/100 million population. Early diagnosis and management of clinical manifestations associated with ectrodactyly-ectodermal dysplasia clefting syndrome present a unique challenge. We report a case of this rare disorder in an 11-year-old male patient along with its dental management using a multidisciplinary approach.

Limb deficiency disorders are rare, etiologically heterogeneous skeletal dysplasias that occur as an isolated anomaly or as a part of a syndrome. The term limb deficiency incorporates both absence and size reduction of any of the 120 human limb bones, with around 205 identified abnormalities. Congenital absence of tibia is a rare and severe lower limb malformation with an incidence of approximately 1:1,000,000 live births. Absence of tibia with ectrodactyly (lobster claw deformity) or tibial hemimelia with split hand/foot malformation (TH-SHFM) or Gollop-Wolfgang complex is a rarer malformation with highly variable manifestations.

Copy number variation in loss of 7q21 is a genetic disorder characterized by split hand/foot malformation, hearing loss, developmental delay, myoclonus, dystonia, joint laxity, and psychiatric disorders. Osteogenesis imperfecta caused by whole gene deletions of COL1A2 is a very rare condition. We report a Turkish girl with ectrodactyly, joint laxity, multiple bone fractures, blue sclera, early teeth decay, mild learning disability, and depression. A copy number variant in loss of 4.8 Mb at chromosome 7 (q21.2q21.3) included the 58 genes including DLX5, DLX6, DYNC1I1, SLC25A13, SGCE, and COL1A2. They were identified by chromosomal microarray analysis. We compared the findings in our patients with those previously reported. This case report highlights the importance of using microarray to identify the genetic etiology in patients with ectrodactyly and osteogenesis imperfecta.

Background/aim Bone tissue engineering is an emerging field of regenerative medicine that holds promise for the restoration of bones affected by trauma, neoplastic diseases, and congenital deformity. During the past decade, bone tissue engineering has evolved from the use of biomaterials that can only replace small areas of damaged bone, to the use of scaffolds in which grafts can be seeded before implantation. This case report proposes an alternative option for a veterinary patient suffering from ectrodactyly, which is one of several congenital deformities in dogs. A 2-month-old male toy poodle dog with ectrodactyly was treated using several stages of surgery involving pancarpal arthrodesis, limb lengthening, and bone tissue engineering techniques. Results and conclusion Over a period of 2 years, the operated limb gained almost the same function as the contralateral limb. Bone tissue engineering techniques can be used for the treatment of congenital deformities in dogs.

Klippel–Trenaunay syndrome is a rare disease with a classic triad of port wine stains, varicose veins, and bony and soft tissue hypertrophy of an extremity. The quality of life in these patients is significantly affected, making the prenatal diagnosis of Klippel–Trenaunay syndrome important. We present four prenatally diagnosed cases of this anomaly with a unique case of ectrodactyly of the hand in foetus with Klippel–Trenaunay syndrome. Such a combination has not been previously reported prenatally. A review of the literature for similar cases is also presented.

Background. Evaluation of the result of functional prosthetics in patients with different upper limb defects is a topical problem of modern prosthetics. Providing patients with non-functional hand stumps with functional prostheses is not wide-scale and refers to atypical and experimental prosthetics. While new functional prosthetic hands appear, there is no algorithm for evaluating the results of prosthetics. Aim. This study aimed to evaluate the result of functional prosthetics in children with congenital defects of the hand and fingers by active prostheses. Materials and methods. We observed 67 children with congenital hand defects, of which 22 were included in the experimental prosthetics group. Bench test station was used for an objective assessment of the residual function of the hand. The booth imitated the tasks of an international competition for the users of Cybathlon rehabilitation equipment and allowed users to perform a series of tests, for each of which a certain number of evaluation points were awarded. Samples at the stand were supplemented with a subjective assessment of the function of the hand using the DASH questionnaire validated in Russia. Results. The best subjective assessment of the supply of an active prosthetic hand was determined in the patients with underdeveloped hand similar to the truncation of the hand proximal to the metacarpophalangeal joints. The lowest functionality score of the active prosthetic hand was obtained in cases of ectrodactyly and hypoplasia of 1–5 fingers, which was associated with a high residual functionality of the hand. Conclusions. In addition to training functions, the developed bench test station serves a diagnostic function as it evaluates the results of functional prosthetics in patients with upper limb defects in different levels, including defects on the hand and fingers. The results of the study on the station correlate with the results of the DASH questionnaire.

Purpose Glaucoma is the leading cause of vision loss in eyes with Boston Keratoprosthesis (KPro). Glaucoma drainage devices (GDDs) have been shown to be effective in controlling glaucoma with KPro. Cicatricial conjunctival disease with forniceal shortening is a major challenge and limitation to the use of GDD. In our series, we report the success of fornix reconstruction in cicatricial ocular surface disease as a staged procedure prior to a combined KPro/GDD surgery. Methods Retrospective case series involving 4 eyes with surface cicatricization. Three patients with chemical burns and one patient with Ectrodactyly Ectodermal Dysplasia-Clefting syndrome. Preoperative data, surgical interventions, and clinical outcomes were reviewed. Conclusion This series represents the first report of fornix reconstruction for combined KPro/GDD surgery. Fornix reconstruction with the aid of AMT with or without OMM grafting is a relatively safe and effective way to manage complex cicatricial surface disease associated with corneal scarring and glaucoma, allowing for subsequent successful implantation of GDD and KPro in cases that were otherwise poor surgical candidates.

Spilt Hand/Foot Malformation with Long-bone Deficiency (SHFMLD) is a rare heterogeneous group of limb malformations characterised by absence/hypoplasia and/or median cleft of hands and/or feet associated with long bone abnormalities, most frequently tibia. This case report described two sisters with congenital limb defects born to healthy consanguineous parents. The six-year-old girl did not had both radii and the left fibula. There was a cleft in the left hand and the right foot. She had one digit in her right upper limb, but did not have the left foot. The four-year-old girl had short four limbs, bilateral tibial aplasia with single digit in all limbs. Both parents were normal, and no other similar cases was reported in the family. According to the authors' best knowledge, these two cases are the first published cases in Yemen with the SHFMLD, but they need a genetic study to determine their genetic profile.

Our findings expand the known clinical features of trisomy 13 by including ectrodactyly as a possible Trisomy 13‐associated limb malformation. We highlight the importance of performing antenatal genetic test to establish more specific treatment plan.

Simple Summary Congenital limb defects are sporadically encountered in dogs during normal clinical practice. Literature concerning their diagnosis and management in canine species is poor. Sometimes, the diagnosis and description of congenital limb abnormalities are complicated by the concurrent presence of different malformations in the same limb and the lack of widely accepted classification schemes. In order to improve the knowledge about congenital limb anomalies in dogs, this report describes the clinical and radiographic findings in four dogs affected by unusual congenital forelimb defects, underlying also the importance of reviewing current terminology. Abstract Four dogs were presented with thoracic limb deformity. After clinical and radiographic examinations, a diagnosis of congenital malformations was performed for each of them. In one case, a deformity involving both the radial and ulnar side of the distal limb was observed. Based on clinical and radiological evaluations, a diagnosis of postaxial terminal longitudinal ulnar hemimelia was performed. The term ectrodactyly was used to refer different malformations characterized by skin and soft tissue separation of the distal forelimb observed in two dogs. Simple complete uncomplicated syndactyly of the right forelimb, and complex incomplete uncomplicated syndactyly of the left forelimb were diagnosed in the fourth case. To the authors’ knowledge, ectrodactyly and simple complete uncomplicated syndactyly are very uncommon anomalies in companion animals and have been rarely documented. Moreover, postaxial terminal longitudinal ulnar hemimelia has still not been reported in dogs.

Introduction There are various genes that affect craniofacial development and among the important genes that affect jaw development is distal-less homeobox (DLX) 6 genes. The present study was carried out to determine the role of DLX6 gene variations in mandibular deficiency. Methods Thirty subjects having retrognathic mandible were evaluated by clinical examination and assessed using lateral cephalometric radiographs based on cephalometrics for orthognathic surgery (COGS) analysis of hard tissue with N-Pog parameters being less than -13 mm. For the same subjects, saliva samples were taken and sent to biotechnology labs for genetic evaluation. DNA was isolated from salivary samples using a DNA extraction kit and was subjected to polymerase chain reaction (PCR) amplification and sequencing. Single nucleotide polymorphisms (SNP) analysis was done to assess the role of DLX6 gene in these study subjects. Results All 30 subjects showed N-POG parameters of COGS analysis for hard tissue to be less than -13mm, confirming retrognathic mandible. SNP analysis of subjects showed no SNPs in any EXON of the DLX6 gene for all 30 study samples. Conclusion No variations in DLX6 gene were found in the present study. Further studies are required to investigate other genes that could be involved in the cause of retrognathic mandible with a larger sample size and to include subjects in the sample having features other than mandibular retrognathia like hearing loss, abnormal pinnae, ectrodactyly, cleft palate, developmental delay and abnormal teeth to determine the contribution of DLX6 gene variations in mandibular deficiency.

In 2020, we had reported one of the few cases of trisomy 13 with ectrodactyly, a rare form of limb deformity. Herein, we report another newborn who suffered from trisomy 13 and ectrodactyly. The patient also possessed another unusual manifestation of trisomy 13, congenital diaphragmatic hernia, a life- threatening pathology.

Ectrodactyly is a rare anomaly seen in the appendicular skeleton and characterized by a cleft or split between bone and soft tissue in the distal regions of the extremities. Ectrodactyly may be associated with the absence and hypoplasia of several carpal-metacarpal bones, phalanx duplication, or metacarpal synostosis. In this case report, a 2-years-old mixed breed male dog was presented withhold up the left forelimb and inspectional abnormality with a cleft. In the radiographic images, it was observed that the fourth phalanx and the fourth distal carpal bone were absent in the related extremity, the cleft extended up to the carpal joint and there was an incongruity between the radius and ulna. The cleft between the metacarpal bones was stabilized using 2 lag screws and corticocancellous bone graft. The incongruity between the carpal joints was eliminated by pancarpal arthrodesis and ulna ostectomy was performed for the incongruity between radius and ulna. It has been observed that postoperative physical therapy exercises with correlated methods have positive long-term results in the related extremity., Ektrodaktili, apendiküler iskelette görülen nadir bir anomali olup, ektremitelerin distal bölgelerinde kemik ve yumuşak doku arasında şekillenen yarık ya da bölünme ile karakterizedir. Ektrodaktili birkaç karpal-metacarpal kemiğin yokluğu/hipoplazisi, phalanks duplikasyonu ya da metacarpal sinostos ile ilişkili olabilir. Bu olgu sunumunda 2 yaşında, melez ırk, erkek bir köpek, sol ön ekstremitesini yukarıda tutma ve dış bakıda gözlenebilen bir yarık şikayeti ile getirildi. Alınan radyografik görüntülerde ilgili ekstremitede dördüncü phalanx’ın ve dördüncü distal carpal kemiğin olmadığı, yarığın carpal ekleme kadar uzandığı ve radius ile ulna arasında uyumsuzluk olduğu görüldü. Metacarpal kemikler arasındaki yarık 2 adet lag vidası ve kortikokansellöz kemik grefti kullanılarak stabilize edildi. Carpal eklemler arasındaki uyumsuzluk pancarpal artrodez yöntemi ile giderildi ve radius ile ulna arasındaki uyumsuzluk için ulna ostektomisi uygulandı. Uygulanan korrektif yöntemler ile operasyon sonrası uygulanan fizik tedavi egzersizlerinin, ilgili ekstremitedeki uzun dönem sonuçlarının olumlu olduğu gözlenmiştir.

There is growing evidence that TP63 is associated with isolated as well as syndromic premature ovarian insufficiency (POI). We report two adolescent sisters diagnosed with undetectable ovaries, uterine hypoplasia, and mammary gland hypoplasia. A novel paternally inherited nonsense variant in TP63 [NM_003722.4 c.1927C > T,p.(Arg643*)] in exon 14 was identified by exome sequencing. One of the syndromes linked to TP63 is limb mammary syndrome (LMS), an autosomal dominant inherited disorder characterized by ectrodactyly, hypoplasia of mammary-gland and nipple, lacrimal duct stenosis, nail dysplasia, dental anomalies, cleft palate and/or cleft lip and absence of skin and hair defects. The TP63 variant segregated with symptoms of LMS in the family, however, no affected individual had limb defects. The phenotype reported here represents a novel syndromic phenotype associated with TP63. Reported cases with TP63 associated POI are reviewed.

Split-hand/foot malformation (SHFM) is a genetic limb anomaly disturbing the central rays of the autopod. SHFM is a genetically heterogeneous disorder with variable expressivity inherited as syndromic and nonsyndromic forms. We provide an update of the clinical and molecular aspects of nonsyndromic SHFM. This rare condition is highly complex due to the clinical variability and irregular genetic inheritance observed in the affected individuals. Nonsyndromic SHFM types have been reviewed in terms of major molecular genetic alterations reported to date. This updated overview will assist researchers, scientists, and clinicians in making an appropriate molecular diagnosis, providing an accurate recurrence risk assessment, and developing a management plan.

Hartsfield syndrome (HS: OMIM 615465) is a rare congenital disease associated with a mutation of the fibroblast growth factor receptor 1 gene (FGFR1) with the main features of holoprosencephaly and ectrodactyly. Patients with HS also present with endocrinological deficits, such as isolated hypogonadotropic hypogonadism and central diabetes insipidus. Although there are several studies on infancy/childhood history, there is no study of infant/childhood/adolescent/young adult HS natural history and endocrinological findings. Here, we report a male patient with HS associated with a novel de novo FGFR1 mutation (c. 1868A > C). The endocrinological profile was evaluated at ages 1 and 31 years. This long-term follow-up study highlights functional changes in the posterior pituitary gland and features of bone metabolism disorder. We also describe the anterior pituitary function. To our knowledge this is the first description of the natural history of an HS patient through birth to young adult age. Although the HS infants reported in the literature develop central diabetes insipidus, little is known about the serial changes in pituitary gland function during growth in HS patients. In this study we describe an adult patient with HS who showed improvement of hypernatremia during early adulthood. In addition, we emphasize the importance of prevention and treatment of osteoporosis in HS.

Background Cleft foot is a very rare congenital anomaly, which is characterized by central rays deficiency of the foot. It is also known as split foot or ectrodactyly of the foot, and it is very often combined with splitting of the hands. The defect develops due to insufficient activity of the median apical ectodermal ridge, which leads to an increase in cell death or a decrease in cell proliferation. Due to the rarity of the pathology, there are few papers on the surgical treatment of this congenital foot disease, and publications to date concern the treatment of children. Case summary We present a clinical case of congenital splitting of the feet and hands in a 31-year-old woman and a long-term result of foot treatment using the minimal arrangement of the Ilizarov apparatus. The patient had paternal inheritance of the trait. After the surgical treatment, cosmetic view and functional condition of the foot were improved and persisted two years after intervention. There were no complications in the treatment process. Conclusion The possibility of dosed control and stable fixation of the foot rays made it possible to create favorable conditions for the healing of the central wound and the closure of the segment splitting without complications. The long-term outcome of the treatment of foot congenital splitting using the proposed Ilizarov apparatus arrangement has shown its effectiveness. Our approach should be considered as an option of treatment in similar cases.

Background: Trisomy 18 is one of the most prevalent chromosomal aberrations in newborns, with characteristic features of internal organs such as heart and kidney abnormalities, as well as craniofacial and musculoskeletal anomalies. We present a rare case of trisomy 18 with atypical features of split-hand/split-foot malformation (SHFM).Case Presentation: A four-months-old baby was brought to hospital with dyspnea and history of multiple congenital anomalies (MCA). Abnormalities found including brachycephaly, facial dysmorphisms, split hands and split feet. Other anomalies were atrial and ventricular septal defects, umbilical hernia, and right lung atelectasis. Based on physical examination and additional workups, SHFM was suspected. Genome-wide array analysis revealed gain on entire chromosome 18. Only few cases of trisomy 18 with SHFM have been reported, with split feet as the most findings. Conclusion: This case represents SHFM as a unique limb involvement in patient with trisomy 18, a valuable finding to be taken into account in trisomy 18 features. Careful examination and diagnosis as well as subsequent genetic counseling are granted, and routine cytogenetic analysis is vital as a first-tier diagnostic workup on patient with MCA.

OBJECTIVE To review an institutional experience with the surgical and clinical management of acquired middle ear cholesteatoma in patients with ectrodactyly, ectodermal dysplasia, cleft lip/palate (EEC) syndrome. STUDY DESIGN Retrospective chart review. SETTING Tertiary referral center. PATIENTS Eight patients with medical history significant for EEC syndrome who underwent surgery for acquired middle ear cholesteatoma between 1996 and 2016. INTERVENTION(S) Appropriate surgical interventions at the time of admission. MAIN OUTCOME MEASURE(S) History of ventilation tube insertion, status of the contralateral ear, surgical technique, cholesteatoma recidivism, presence of postoperative external auditory canal stenosis, pre and postoperative audiograms. RESULTS Cholesteatoma was diagnosed in all patients, 3 (37.5%) unilateral and 5 (62.5%) bilateral, totalizing 13 ears. Six ears (46.2%) underwent a canal wall up mastoidectomy but required conversion to a canal wall down technique in a second procedure due to recurrent cholesteatoma. In the remaining seven ears (53.8%) a canal wall down mastoidectomy was performed. Of all meatoplasty performed, seven (53.8%) evolved with stenosis of the external auditory canal. CONCLUSIONS Our results suggest that most patients with EEC syndrome and middle ear cholesteatoma should be considered for a canal wall down mastoidectomy due to extensive disease and a high rate of recidivism. In addition, a high percentage of postoperative stenosis of the external auditory canal was found in this group.

Key Clinical Message We report a patient who was followed for a long time under an ectrodactyly ectodermal dysplasia‐clefting (EEC) syndrome and was subsequently diagnosed with a 19q13.11 microdeletion. After a review of the related literature, we suggest testing patients with EEC for 19q13.11 microdeletion and include WTIP and UBA2 to a minimal overlapping region.

BACKGROUND: Robinow Syndrome is an extremely rare genetic disorder characterised by abnormalities in head, face and external genitalia. This disorder exists in dominant pattern with moderate symptoms and recessive pattern with more physical and skeletal abnormalities. It was first introduced by Menihard Robinow in 1969. It was related to chromosome 9q22 ROR2 gene related to bone and cartilage growth aspects.CASE PRESENTATION: A 17-year-old Egyptian male presented to National Research Centre Orodental genetics Clinic with typical features of short stature and facial dysmorphism weighted 50 Kg and measured 150 cm height complaining of facial disfigurement. There was no significant prenatal history, and family history was negative for congenital disabilities and genetic disorders. Clinical examination revealed macrocephaly and special facial features as prominent forehead, deformed ear pinna, hypertelorism, flat nasal tongue tie, deficient malar bone, bow-shaped upper and lower lips and dimpled chin. Orally the patient suffered from tonetie, gingival hypertrophy and dental malalignment. The orthopantomogram showed multiple impacted teeth. The physical examination revealed that the patient had deformed spine, short limbs with ectrodactyly, micropenis & hypospadias. Surgical management included correction of midface deficiency with zygomatic augmentation, closed rhinoplasty for the broad nose, lips muscles release and tongue tie relief. The patient is currently undergoing orthodontic treatment for his teeth.CONCLUSION: Improvement of facial features and a good psychological impact on the patient and his family.

Congenital anomalies of the upper limbs are rare and etiologically heterogeneous. Herein, we report a male infant with non-syndromic bilateral Type Vb ulnar longitudinal dysplasia with radiohumeral synostosis (apparent humeral bifurcation), and bilateral oligo-ectro-syndactyly who was born following an uncomplicated pregnancy, with no maternal use of prescription or illicit medication. Array CGH (60,000 probes) and chromosomal breakage analysis (DEB) were normal. Similar appearances have been reported in children exposed to thalidomide or cocaine, but sporadic patients have also been reported without a prior history of exposure to known teratogens.

Objective: The aim of the report is to highlight importance of careful ultrasound examination and genetic counsel in case of split hand/foot prenatal diagnosis. Evaluation of the accompanying long bone deficiency indicates that array comparative genomic hybridization (aCGH) should be used. Case report: We present a prenatal diagnosis of split hand/foot malformation with long bone deficiency type 3 (SHFLD3) in a patient suffering from congenital limb anomalies but without previous molecular diagnosis. Genetic consultation and prenatal testing were offered. While karyotype was normal, aCGH revealed microduplication in locus 17p33.3. Microarray analysis was carried out also in pregnant patient and her asymptomatic mother and gave positive results on both. Conclusion: Prenatal diagnosis of SHFLD3 either imaging or cytogenetic is possible. Both methods should be used to make a correct diagnosis. Due to reduced penetrance of SHFLD3 not all individuals carrying microduplication present clinical findings. Therefore, pedigree analysis and genetic counsel is important for whole family and not only for affected members. Advances in genetics may allow to establish exact diagnosis in previously undiagnosed patients. Keywords: Ectrodactyly, Genetic counsel, Microduplication, Split hand/foot, Tibial aplasia

Based on the analysis of literature sources, an attempt to summairze existing information concerning malformations of the foot skeleton is made and their classification and interpretation in alphabetical order are suggested. Congenital malformations of the foot can be divided into typical (independent nosological forms) and atypical (combined with other abnormalities or diseases). The most common congenital malformations of the foot skeleton are: clubfoot, platypodia, polydactyly, syndactyly and ectrodactyly.

RESUMO Objetivo: EEC é um acrônimo para uma síndrome autossômica dominante caracterizada clinicamente por ectrodactilia (E), displasia ectodérmica efissura labiopalatal (C). Nosso objetivo foi relatar um caso raro de irmãos afetados pela síndrome de ectrodactilia, displasia ectodérmica efissura labiopalatal (EEC) com pais hígidos. Descrição do caso: O paciente era o terceiro filho de pais jovens e hígidos, os quais não apresentavam nenhuma anomalia menor ou maior de mãos e pés ou anomalias de pele, cabelos e dentes. O casal tinha história prévia de duas crianças com malformação de mãos e pés, similar à do paciente. O primeiro foi natimorto e o segundo, prematuro, falecendo nos primeiros dias de vida, pelas consequências da prematuridade. Após o nascimento, o paciente apresentou desconforto respiratório, com necessidade de intubação orotraqueal e ventilação mecânica. No exame físico, verificaram-se a presença de fissura labiopalatal e ectrodactilia de mãos e pés, com ausência do segundo e terceiro dedos em ambas as mãos e defeitos de redução acometendo principalmente o segundo dedo dos pés. A criança apresentou pneumotórax e parada cardiorrespiratória, morrendo com 1 mês e 26 dias de vida. Comentários: Descrevemos aqui um caso de irmãos com síndrome EEC, indicativo de mosaicismo germinativo. Na revisão da literatura, observaram-se apenas três relatos similares. Este caso reforça a possibilidade do mosaicismo germinativo ser um mecanismo de herança mais comum do que se acreditava previamente para casos da síndrome EEC.

Fryns syndrome (FS, OMIM#194050) is a rare lethal autosomal recessive disorder with unknown genetic defect, manifested the distinct complex of the multiply congenital abnormalities (MCA), including diaphragmatic hernia. There was made the world literature overview for the FS phenotypic features, clinical and genealogical data of the published familial cases, ultrasound and morphological characteristics of affected fetuses. Aim . Analysis of the clinical, morphological and prenatal ultrasound data of 12 FS cases, detected in Belarus during 2009-2018 years, and families’ reproduction results. Material and methods . Genetic counseling of 10 families with affected outcome was performed. All the pregnants underwent the combined (biochemical and ultrasound) screening. Prenatal and postnatal cytogenetical studies (GTG-banding) and the morphological investigations of the 10 aborted fetuses and 2 deceased infants were fulfilled. Results and Discussion . All the patients presented typical FS phenotypic features correlated with the diagnostic criteria. The spectrum of prenatal findings diagnosed at 1-st trimester included nuchal skin enlargement/cystic hygroma (5 cases), at the 2-ed trimester – diaphragmatic hernia (11 cases), omphalocele (1), other malformations (4 fetuses). The facial dysmorphisms (coarse face) were detected in all the patients. Lungs hypoplasia was found in all cases, 5 patients additionally dysplayed other abnormalities: pulmonary sequestration, cystic-adenomatoid malformation, lobular aplasia. Characteristic phalanges and nails hypoplasia or aplasia were registered in 11 cases, 3 sibs presented rare malformations – polydactyly (hands) and ectrodactyly (feet). Associated malformations spectrum included cleft palate, brain abnormalities (ventricular dilatation, arhinencephaly), cardiac defects, omphalocele, Meckel diverticule, hydronephroses, renal cysts, bicornuate uterus and hypospadia. The familial case with 3 affected sibs demonstrated a similarity in main diagnostic criteria. The couples reproduction analysis illulustrated a serious failure. Outcome of 29 pregnancies were as follows: 12 – FS cases, 4 – miscarries at 1-st trimester, 11 – healthy offspring and 2 cases – pregnancies are going on currently (both fetuses without malformations). Conclusion . Clinical diagnosis of FS may be noted in patients (either fetuses or newborns), which display the conjunction of typical MCA pattern with a normal karyotype. Additional investigations must be used in order to exclude the associated abnormalities if diaphragmatic hernia has been detected in fetus. In our opinion polydactyly and ectrodactyly may be added to the FS phenotypic spectrum.

P63 is a major transcription factor regulating skin development and homeostasis. It controls many genes involved in cell proliferation, adhesion, and early differentiation. P63 is mutated in several rare syndromes called p63-related ectodermal dysplasia syndromes (ED). The main forms are EEC and AEC syndromes due to p63 missense mutations on the DBD and SAM domains, respectively. ED patients display many developmental defects, including ectrodactyly, clef/lip palate, and ectodermal dysplasia, while AEC patients suffer from severe skin erosions that not always heal. We have previously showed that ED-derived iPSC display altered epidermal commitment. P63 belongs to the p53 gene family sharing similar structural domains. We found that ED-iPSC epidermal commitment can be rescued by a p53-reactivating compounds called PRIMA-1MET, also named APR-246 and currently used in anticancer clinical trials. Here, we established primary epidermal culture from two AEC children (S.F. and Y.M.) suffering from persistent skin erosions at age of 9 and 15, respectively. These patients carry missense mutations on the SAM domain (I576T and I537T). We found that primary keratinocytes (KCs) isolated from these AEC patients underwent altered epidermal differentiation that was rescued by PRIMA-1MET treatment. It prompted us to formulate the compound onto a cream that was topically applied on the right hand of one patient and on the scalp of the second patient. In both cases, the daily treatment allowed re-epithelialization of the eroded skin and a drastic loss of pain after few weeks, improving quality of life. Normally, mutant p63 exerts a dominant-negative effect, mainly through the formation of aggregate with WT p63 and p73. PRIMA-1MET did not reduce protein aggregation while enhancing cell differentiation, suggesting that PRIMA-1MET targets cell differentiation and not p63 activity directly. In conclusion, we propose that repurposing of the antitumoral PRIMA-1MET compound could become a general treatment of AEC skin erosions.

Split hand/split foot malformation (SHFM) or ectrodactyly is characterized by a deep median cleft of the hand or foot, hypoplasia or aplasia of the metacarpals, metatarsals, and phalanges. It is a clinically and genetically heterogeneous group of limb malformations. This study aimed to identify the pathogenic variant in a consanguineous Pakistani family with autosomal recessive SHFM. Peripheral blood samples were obtained, DNA was extracted, WNT10B coding and noncoding regions were PCR amplified and Sanger sequencing was performed using workflow suggested by Thermo Fisher Scientific. A novel homozygous nonsense variant (c.1098C>A; p.Cys366*) was identified in the WNT10B gene in the index patients, which probably explains SHFM type 6 in this family in comparison with similar data from the literature.

Case of prenatal ultrasound diagnosis of EEC syndrome at 14 weeks of gestation is presented. A rare feature of the case was the ectrodactyly of all limbs.

Millions of people are suffering from different types of amputation problems around the world. A Large number of patients cannot afford automated prosthesis limbs as they are extremely expensive. In under developed and developing countries, the problem is more acute. On the other hand, different people have distinctive prosthetic needs as amputations differ from person to person. So, this study approaches towards the development of a cost effective need based customized prosthesis for an upper limb congenital amputee patient. 3D printing technology allows to change and customize the shape of the prosthesis according to patient’s needs, as well as makes the limbs affordable. In this study, the developed prosthesis was designed for a child with Ectrodactyly upper limb amputation. The prosthesis was designed keeping the patient’s limitations under consideration, and enabling her to use her amputated limb to engage in tasks beyond her limitations.

Introduction FATCO (Fibular Aplasia, Tibial Campomelia and Oligosyndactyly) syndrome is a rare descriptive diagnosis first defined by Courtens et al. in 2005, who recognised a comparable pattern of malformations with his own case and 4 others described in the literature.1 Aetiology remains unknown, however defects involved in SHH (Sonic hedgehog) gene expression have been proposed.2 Case description We report on a term male infant born with severe malformations. On examination, there was absence of the left radius and ulna, bilateral anterior angulation of lower limbs with skin dimpling overlying. Both ankle joints were dysplastic and there was oligosyndactly of both feet. Right upper limb was normal. X-rays of the limbs revealed dysplastic tibiae, absence of both fibulae, a right foot containing 3 ossified metatarsals with 2 formed digits, and a left foot with a single ossified metatarsal and two soft tissue digits with small bony elements. The infant had no other associated anomalies, and is developmentally appropriate at 1 year. Management included Symes amputation, prosthetics and following genetic referral, FATCO syndrome was suggested as the best fitting diagnosis. Whole genome sequencing of infants blood is currently being performed. Discussion This is an important case to report as there are very few descriptions in the literature,1–5 In keeping with the majority of reports, this case appears to be sporadic and development is normal.1,3,4 Our case is male, keeping with preponderance.1,3–5 Treatment aims at optimising functionality of limbs and stabilisations of joints.1–5 References Courtens W, Jespers A, Harrewijn I, Puylaert D, VAnhoenacker F. Fibular aplasia, tibial campomelia, and oligosyndactyly in a male newborn infant: a case report and review of the literature. Am J Med Genet A 2005;134(3):321–5. Bieganski T, Jamsheer A, Sowinska A, Baranska D, Niedzielski K, Kozlowski K, Czarny-Ratajczak M. 2012. Three new patients with FATCO: Fibular agenesis with ectrodactyly. Am J Med Genet Part A 158A:1542–1550. Petricevic J, Curic A, Karaman I, Forempoher G, Definis-Gojanovic M ( 2017) First Case of Bilateral Fibular Aplasia, Tibial Campomelia and Oli- godactyly Syndrome (FATCO Syndrome). J Clin Stud Med Case Rep 4: 046. Karaman A, Kahveci H. A male newborn infant with Fatco syndrome (fibular aplasia, tibial campomelia and oligodactyly): a case report. Genet Couns 2010;21(3):285–8. Goyal, Navendu, et al. ‘FATCO Syndrome Variant - Fibular Hypoplasia, Tibial Campomelia and Oligosyndactyly –– A Case Report.’ Journal of Clinical and Diagnostic Research: JCDR 8.9 (2014): LD01–LD02. PMC. Web.

Split-hand/foot malformation (SHFM) is a genetically heterogeneous congenital limb malformation typically limited to a defect of the central rays of the autopod, presenting as a median cleft of hands and feet. It can be associated with long bone deficiency or included in more complex syndromes. Among the numerous genetic causes, WNT10B homozygous variants have been recently identified in consanguineous families, but remain still rarely described (SHFM6; MIM225300). We report on three novel SHFM families harboring WNT10B variants and review the literature, allowing us to highlight some clinical findings. The feet are more severely affected than the hands and there is a frequent asymmetry without obvious side-bias. Syndactyly of third-fourth fingers was a frequent finding (62%). Polydactyly, which was classically described in SHFM6, was only present in 27% of patients. No genotype-phenotype correlation is delineated but heterozygous individuals might have mild features of SHFM, suggesting a dose-effect of the WNT10B loss-of-function.

Hartsfield syndrome is a rare clinical entity characterized by holoprosencephaly and ectrodactyly with the variable feature of cleft lip/palate. In addition to these symptoms patients with Hartsfield syndrome can show developmental delay of variable severity, isolated hypogonadotropic hypogonadism, central diabetes insipidus, vertebral anomalies, eye anomalies, and cardiac malformations. Pathogenic variants in FGFR1 have been described to cause phenotypically different FGFR1-related disorders such as Hartsfield syndrome, hypogonadotropic hypogonadism with or without anosmia, Jackson–Weiss syndrome, osteoglophonic dysplasia, Pfeiffer syndrome, and trigonocephaly Type 1. Here, we report three patients with Hartsfield syndrome from two unrelated families. Exome sequencing revealed two siblings harboring a novel de novo heterozygous synonymous variant c.1029G>A, p.Ala343Ala causing a cryptic splice donor site in exon 8 of FGFR1 likely due to gonadal mosaicism in one parent. The third case was a sporadic patient with a novel de novo heterozygous missense variant c.1868A>G, p.(Asp623Gly).

Introduction: Cleft hand or Ectrodactyly or Split Hand is a rare form of congenital hand disorder in which there is deficiancy of one or more central rays of the hand. The hand presents with a V-shaped gap situated in the centre of the palm. The condition may occur alone or maybe associated with anomalies of foot, syndactly, polydactyly, triphalangeal thumb, transverse bones in the hand or maybe part of Ectrodactyly Ectodermal dysplasia Cleft (ECC) Syndrome. Aims and Objectives: To find out the sex ratio and incidence of laterality (unilateral or bilateral) of cleft hand in North East population of Assam. Subjects and Methods: This study included 31 children between age group of 3 years to 8 years with hand deformities who were brought to the Plastic Surgery Department, Gauhati Medical College, Guwahati for aesthetic correction within a time span of 2 years. Only those cases who had central defects of hand were included & those with other syndromic anomalies were excluded. For this detailed clinical and radiological examination was done to evaluate the extent of bone or tissue involvement and to find out any syndromic association of the condition. Results: Out of 31 cases, 10 cases were had Unilateral and 21 cases had Bilateral Cleft Hands. It was seen that out of 31 cases, 22 were males and only 09 were females indicating that male to female ratio of the deformity is 2.44 .Thus, males were more affected than females. Conclusion: Most of the cases presented with absence of the middle finger and central tissue of the affected hand since birth. The embryological basis has been highlighted to throw light into such a catastrophe where both males and females were affected and showed unilateral or bilateral involvement of the hand leading to cosmetic and functional debility. Therefore, the study revealed that males were more affected than females and bilateral involvement of the hands were common than unilateral involvement.

Background Split hand/foot malformation (SHFM) is a group of congenital skeletal disorders which may occur either as an isolated abnormality or in syndromic forms with extra-limb manifestations. Chromosomal micro-duplication or micro-triplication involving 17p13.3 region has been described as the most common cause of split hand/foot malformation with long bone deficiency (SHFLD) in several different Caucasian and Asian populations. Gene dosage effect of the extra copies of BHLHA9 gene at this locus has been implicated in the pathogenesis of SHFLD. Case presentation The proband was a female child born to non-consanguineous parents. She was referred for genetic evaluation of bilateral asymmetric ectrodactyly involving both hands and right foot along with right tibial hemimelia. The right foot had fixed clubfoot deformity with only 2 toes. The mother had bilateral ectrodactyly involving both hands, but the rest of the upper limbs and both lower limbs were normal. Neither of them had any other congenital malformations or neurodevelopmental abnormalities. Genetic testing for rearrangement of BHLHA9 gene by quantitative polymerase chain reaction confirmed the duplication of the BHLHA9 gene in both the proband and the mother. Conclusions We report the first Sri Lankan family with genetic diagnosis of BHLHA9 duplication causing SHFLD. This report along with the previously reported cases corroborate the possible etiopathogenic role of BHLHA9 gene dosage imbalances in SHFM and SHFLD across different populations.

Ectrodactyly ectodermal dysplasia with clefting is a rare syndrome resulting from TP63 gene mutations. It is inherited in autosomal dominant manner or as a de novo transfiguration. It is characterized by a triad of ectodermal dysplasia, ectrodactyly, and facial clefts. This report represents a clinical case of 5 years and 6 months-old male child with ectrodactyly ectodermal dysplasia cleft lip and palate syndrome requiring treatment of his carious teeth. After history taking and clinical examination, the necessary treatment was provided under general anesthesia due to the definitely negative behavior of the child. The treatment outcomes had a positive impact on the behavior and acceptance to dental treatment. This was evidenced by completion of the prosthetic and space management appliances on the dental chair. The child's quality of life was consequently improved. This was evidenced by the reduced response scores of the child perception questionnaire (CPQ11-14 ) after treatment. This report highlighted the value of proper diagnosis and fulfillment of the unmet dental needs for patients with orofacial syndromes to improve their quality of life.

Ectrodactyly is an exceptional congenital disorder which is seen at the distal part of the limbs and characterized with longitudinal bony and soft tissue clefts. These clefts can include digits, metacarpal bones, carpal joint or radius-ulna. A male, 18 week-old, Turkish Kangal dog was presented with the right forelimb lameness and inspectional abnormality with a long and wide cleft starting from the distal manus to the carpo-metacarpal joint. The long cleft between metacarpal bones was fixed with two lag screws after filling the gap with corticocancellous bone block and fusion podoplasty. Short term clinical results were favourable following the surgery, but long term clinical outcome was less favourable because the dog revealed mild lameness due to the erosion of skin surrounding the digital pads. Finally, this problem was solved by using pad protectors when walking on rough grounds, Ektrodaktili, bacağın distal kısmındaki yumuşak ve kemik dokuda uzunlamasına yarık ile karakterize, ender görülen konjenital bir hastalıktır. Bu yarık; parmakları, metakarpal kemikleri, karpal eklemi ve radius ulna’yı da kapsayabilir. Dört buçuk aylık, Kangal ırkı, erkek bir köpek sağ ön ayağında topallık ve dış bakıda belirlenebilen distalden başlayan ve karpometakarpal ekleme kadar uzanan, uzun ve geniş bir yarık şikayeti ile getirildi. Metakarpal kemikler arasındaki geniş yarık, kortikokansellöz blok kemik grefti ve füzyon podoplastiden sonra iki lag vidası ile stabilize edildi. Operasyonu takiben kısa dönem sonuçları olumlu iken, uzun dönem sonuçlarına bakıldığında, parmakların taban yastıklarının etrafındaki derinin erozyonundan dolayı hafif topallık gözlendi. Sonuç olarak bu problem de sert zeminde yapılan yürüyüşlerde koruyucu ped uygulaması ile çözüldü

Congenital limb deformities are very rare conditions and the knowledge about etiology, pathogenesis, clinical presentation and treatment is still poor. Moreover, many defects are still not reported in veterinary literature. This report documents clinical and radiographic findings in three dogs with congenital deformity involving the distal extremities. Case 1 was affected with bilateral aphalangia of the pedes, case 2 presented a combination of brachydactyly and syndactyly, whereas in case 3 a unilateral ectrodactyly was observed. To the authors’ knowledge, brachydactyly, as well as aphalangia, are very uncommon anomalies and have been rarely documented. Moreover, association between syndactyly and brachydactyly has still not been reported.Keywords: Aphalangia, Brachydactyly, Congenital deformity, Dog, Syndactyly.

The ectrodactyly, ectodermal dysplasia, and cleft lip/palate syndrome 3 (EEC3; OMIM #604292), the Rapp-Hodgkin syndrome (RHS), and various other syndromes are caused by mutations in the TP63 gene, which encodes a p53-like transcription factor. Here, we report on a woman aged 37 years and her daughter aged 3 years with the previously reported c.1028G>A (p.Arg343Gln) mutation in exon 8 of TP63. The mother lacked ectrodactyly, indicating a diagnosis of RHS, whereas the girl presented with all three major features (ectrodactyly, ectodermal dysplasia, clefting) and different minor features (including small and brittle nails, and recurrent conjunctivitis believed to be because of stenotic and blocked nasolacrimal ducts) of the EEC3 syndrome. The EEC and EEC-like syndromes are usually distinguished on the basis of the clinical findings; however, these syndromes show a huge variability in features because of variable expressivity and incomplete penetrance, making the correct clinical assignment difficult. In EEC3 syndrome and RHS, a clustering of mutations in the different domains of TP63 can be observed. Our findings indicate the clinical variability with TP63 mutations and underline that in the case of two syndromes being clinically possible in a patient, the final diagnosis should be assigned only after molecular diagnostics.