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Purpose: The human chromosome 19q13.11 deletion syndrome is associated with a variable phenotype that includes aplasia cutis congenita (ACC) and ectrodactyly as specific features. UBA2 (ubiquitin-like modifier-activating enzyme 2) lies adjacent to the minimal deletion overlap region. We aim to define the UBA2-related phenotypic spectrum in humans and zebrafish due to sequence variants and to establish the mechanism of disease. Methods: Exome Sequencing was used to detect UBA2 sequence variants in 16 subjects in 7 unrelated families. uba2 loss-of-function was modeled in zebrafish. Effects of human missense variants were assessed in zebrafish rescue experiments. Results: 7 human UBA2 loss-of-function and missense sequence variants were detected. UBA2-phenotypes included ACC, ectrodactyly, neurodevelopmental abnormalities, ectodermal, skeletal, craniofacial, cardiac, renal, and genital anomalies. uba2 was expressed in zebrafish eye, brain, and pectoral fins; uba2-null fish showed deficient growth, microcephaly, microphthalmia, mandibular hypoplasia, and abnormal fins. uba2-mRNAs with human missense variants failed to rescue nullizygous zebrafish phenotypes. Conclusion: UBA2 variants cause a recognizable syndrome with a wide phenotypic spectrum. Our data suggest that loss of UBA2 function underlies the human UBA2 monogenic disorder and highlights the importance of SUMOylation in the development of affected tissues.

Syndactyly is the most common limb defect depicting the bony and/or cutaneous fusion of digits. Syndactyly can be of various types depending on the digits involved in the fusion. To date, eight syndactyly-associated genes have been reported, of which HOXD13 and GJA1 have been explored in a few syndactyly but most of them have unknown underlying genetics. In the present study HOXD13, GJA1 and TP63 genes have been screened by resequencing in 24 unrelated sporadic cases with various syndactyly. The screening revealed two pathogenic HOXD13 variants, NM_000523:c.500 A > G [p.(Y167C)], and NM_000523:c.961 A > C [p.(T321P)] in syndactyly type 1b and type 1c, respectively. This is the first report to identify HOXD13 pathogenic variant in syndactyly type 1b and third report in syndactyly type 1c pathogenesis. Furthermore, this study also reports a TP63 pathogenic variant, NM_003722:c.953 G > A [p.(R318H)] in Ectrodactyly and Cleft lip and palate (ECLP). In conclusion, the current study expands the clinical spectrum of HOXD13 and TP63-related disorders.

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.

The extensive clinical and genetic heterogeneity of congenital limb malformation calls for comprehensive genome-wide analysis of genetic variation. Genome sequencing (GS) has the potential to identify all genetic variants. Here we aim to determine the diagnostic potential of GS as a comprehensive one-test-for-all strategy in a cohort of undiagnosed patients with congenital limb malformations. We collected 69 cases (64 trios, 1 duo, 5 singletons) with congenital limb malformations with no molecular diagnosis after standard clinical genetic testing and performed genome sequencing. We also developed a framework to identify potential noncoding pathogenic variants. We identified likely pathogenic/disease-associated variants in 12 cases (17.4%) including four in known disease genes, and one repeat expansion in HOXD13. In three unrelated cases with ectrodactyly, we identified likely pathogenic variants in UBA2, establishing it as a novel disease gene. In addition, we found two complex structural variants (3%). We also identified likely causative variants in three novel high confidence candidate genes. We were not able to identify any noncoding variants. GS is a powerful strategy to identify all types of genomic variants associated with congenital limb malformation, including repeat expansions and complex structural variants missed by standard diagnostic approaches. In this cohort, no causative noncoding SNVs could be identified. Polish National Science Centre [UMO-2016/22/E/NZ5/00270]; Deutsche Forschungsgemeinschaft (DFG)German Research Foundation (DFG) [SP1532/3-1, SP1532/4-1, SP1532/5-1]; Max Planck FoundationFoundation CELLEX; Deutsches Zentrum fur Luft-und Raumfahrt (DLR)Helmholtz AssociationGerman Aerospace Centre (DLR) [01GM1925]; Projekt DEAL Open Access funding enabled and organized by Projekt DEAL. A.J. was supported by the grant from the Polish National Science Centre UMO-2016/22/E/NZ5/00270. M.S. is supported by grants from the Deutsche Forschungsgemeinschaft (DFG) (SP1532/31, SP1532/4-1 and SP1532/5-1), the Max Planck Foundation and the Deutsches Zentrum fur Luft-und Raumfahrt (DLR 01GM1925).

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.

A marginal illustration of a non-ambulatory child in the 14th Century Luttrell Psalter is the earliest currently identifiable image of an individual with Split Hand Split Foot with Long Bone Deficiency (SHFLD). Changes in portrayal of SHFLD over the centuries reflect changes in social perception of disabilities from pious sympathy to scientific curiosity and unfortunately also morbid fascination. Hopefully understanding of the past attitudes toward split hand and foot as reflected in art can help in moving toward acceptance of individuals with this highly visible malformation.

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.

Craniofacial and limb defects are two of the most common congenital anomalies in the general population. Interestingly, these defects are not mutually exclusive. Many patients with craniofacial phenotypes, such as orofacial clefting and craniosynostosis, also present with limb defects, including polydactyly, syndactyly, brachydactyly, or ectrodactyly. The gene regulatory networks governing craniofacial and limb development initially seem distinct from one another, and yet these birth defects frequently occur together. Both developmental processes are highly conserved among vertebrates, and zebrafish have emerged as an advantageous model due to their high fecundity, relative ease of genetic manipulation, and transparency during development. Here we summarize studies that have used zebrafish models to study human syndromes that present with both craniofacial and limb phenotypes. We discuss the highly conserved processes of craniofacial and limb/fin development and describe recent zebrafish studies that have explored the function of genes associated with human syndromes with phenotypes in both structures. We attempt to identify commonalities between the two to help explain why craniofacial and limb anomalies often occur together.

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.

Interstitial 19q13.11 deletions are associated with ectrodactyly, which has recently been linked to loss-of-function of the UBA2 gene. We report a boy with a de novo frameshift mutation in UBA2 (c.612delA (p.(Glu205Lysfs*63)), presenting with ectrodactyly of the feet associated with learning difficulties and minor physical anomalies. We review genotype-phenotype correlations in patients with chromosomal 19q13.11 microdeletions compared to those with intragenic UBA2 mutations. ispartof: EUROPEAN JOURNAL OF MEDICAL GENETICS vol:63 issue:11 ispartof: location:Netherlands status: published

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