Congenital upper limb differences occur in approximately 20-30 per 10,000 live births. These differences frequently prompt reconstructive surgery and may present in isolation or as markers of systemic syndromes. Embryologically, limb development depends on coordinated signaling along the proximal-distal (apical ectodermal ridge/fibroblast growth factor [FGF]), radial-ulnar (zone of polarizing activity/sonic hedgehog), and dorsal-ventral (wingless-related integration site 7) axes, whose disruptions lead to specific phenotypic patterns. Among upper limb differences, those with a well-established genetic basis can be subcategorized as radial longitudinal deficiency, polydactyly, syndactyly, brachydactyly, ectrodactyly, and macrodactyly. Each phenotype exhibits distinctive radiographic features and associated clinical presentations, which guide syndrome-specific diagnosis. Notable genetic associations include TBX5 (Holt-Oram), FANCA (Fanconi anemia), GLI3 (Greig cephalopolysyndactyly), FGFR2 (Apert), and TP63 (ectrodactyly-ectodermal dysplasia clefting), as well as somatic mosaic mutations (eg, PIK3CA, AKT1, and RASA1) linked to overgrowth syndromes (eg, congenital lipomatous overgrowth, vascular differences, epidermal nevi, and spinal/skeletal differences; Proteus; and Parkes-Weber). Recognition of these patterns relies on imaging and targeted genetic testing. Advances in genomic sequencing have clarified the etiologies of previously classified associations, revealing monogenic or mosaic origins. Early and accurate syndromic identification enables coordinated care, informs management planning, and facilitates multidisciplinary collaboration to optimize functional and psychosocial outcomes. The FLNB-related disorders can be divided into two groups of conditions caused by loss of function or gain of function of filamin-B. Biallelic loss-of-function pathogenic variants in FLNB cause spondylocarpotarsal synostosis syndrome (FLNB-SCT). Monoallelic gain-of-function pathogenic variants in FLNB cause a spectrum of phenotypic severity ranging from apparently isolated clubfoot to Larsen syndrome (FLNB-LS), atelosteogenesis type 3 (FLNB-AO3), and atelosteogenesis type 1 (FLNB-AO1), which is perinatal lethal. For the purposes of this GeneReview, the previously described entities Piepkorn dysplasia and boomerang dysplasia are subsumed under the FLNB-AO1 spectrum. FLNB-SCT is characterized by postnatal disproportionate short stature; scoliosis and lordosis due to vertebral fusions; carpal and tarsal synostosis; and, variably, clubfeet, hearing loss, and dental enamel hypoplasia. FLNB-LS is characterized by combinations of congenital dislocations of the hip, knee, and elbow; clubfeet (equinovarus or equinovalgus foot deformities); scoliosis and cervical kyphosis (which can be associated with a cervical myelopathy); short, broad, spatulate distal phalanges; distinctive craniofacial features (prominent forehead, depressed nasal bridge, malar flattening, and widely spaced eyes); vertebral anomalies; and supernumerary carpal and tarsal ossification centers. Individuals with FLNB-LS may also present with midline cleft palate and hearing loss. FLNB-AO1 and FLNB-AO3 are characterized by severe short-limbed dwarfism; dislocated hips, knees, and elbows; and clubfeet. FLNB-AO1 is lethal in the perinatal period. At its most severe, the spectrum of phenotypes assigned FLNB-AO1 can present with perinatal-lethal micromelic dwarfism characterized by flipper-like limbs (polysyndactyly with complete syndactyly of all fingers and toes, hypoplastic or absent first digits, and duplicated intermediate and distal phalanges); macrobrachycephaly; prominent forehead; hypertelorism; and proptosis. Occasional features include cleft palate, omphalocele, and cardiac and genitourinary anomalies. In individuals with FLNB-AO3, survival beyond the neonatal period is possible with intensive and invasive respiratory support. The diagnosis of FLNB-SCT is established in a proband by identification of biallelic loss-of-function pathogenic variants in FLNB by molecular genetic testing. The diagnosis of other FLNB-related disorders (LS, AO1, AO3) is established in a proband by identification of a heterozygous gain-of-function pathogenic variant in FLNB by molecular genetic testing. Treatment of manifestations: Cervical spine instability in asymptomatic infants can be successfully managed with posterior arthrodesis. Function can be stabilized (if not improved) in infants with myelopathic signs by a combination of anterior decompression and circumferential arthrodesis. Hip dislocation in individuals with FLNB-LS usually requires operative reduction. Scoliosis and clubfeet are managed in a routine manner. Anesthetic agents that allow more rapid induction and recovery are preferred in those with laryngotracheomalacia. When possible, cleft palate and hearing loss are best managed by multidisciplinary teams. Surveillance: Annual orthopedic evaluation for progressive scoliosis; feeding and growth assessment for those with cleft palate by a multidisciplinary team; annual audiologic and dental evaluations. Pregnancy management: Delivery of an affected infant has the potential to be complicated by extended breech presentation due to dislocation of the hips and knees. FLNB-SCT is inherited in an autosomal recessive manner. If both parents are known to be heterozygous for an FLNB pathogenic variant, each sib of an affected individual has at conception a 25% chance of inheriting biallelic pathogenic variants and being affected, a 50% chance of inheriting one pathogenic variant and being heterozygous, and a 25% chance of inheriting neither of the familial FLNB pathogenic variants. Heterozygous sibs of a proband with FLNB-SCT can exhibit mild reductions in stature but no other medically significant phenotypic manifestations. Once the FLNB pathogenic variant(s) have been identified in an affected family member, heterozygote testing for at-risk relatives and prenatal/preimplantation genetic testing are possible. FLNB-LS, FLNB-AO1, FLNB-AO3, and FLNB-related apparently isolated clubfoot are inherited in an autosomal dominant manner. Comparatively mild (e.g., FLNB-LS) and severe (e.g., FLNB-AO3) forms of the autosomal dominant FLNB-related disorders can occur in the same family. Some individuals diagnosed with an autosomal dominant FLNB-related disorder have the disorder as the result of a pathogenic variant inherited from a heterozygous or mosaic parent. Some individuals have the disorder as the result of a de novo pathogenic variant (the vast majority of lethal FLNB conditions are the result of de novo pathogenic variants). Each child of a proband who is heterozygous for an FLNB pathogenic variant has a 50% chance of inheriting the pathogenic variant. Each child of a proband with somatic mosaicism for an FLNB pathogenic variant has up to a 50% chance of inheriting the pathogenic variant. Offspring who inherit an FLNB pathogenic variant from a proband with somatic mosaicism may be more severely affected than the proband. Once the FLNB pathogenic variant has been identified in an affected family member, prenatal/preimplantation genetic testing are possible.

The Oberg-Manske-Tonkin (OMT) classification established excellent reliability scores in several validation studies. However, one study published in 2022 found much lower scores in a subanalysis of their sample when very simple anomalies were excluded. Our study assessed the reliability of the OMT among physicians with a different background, all involved in congenital hand anomaly care, and analyzed codes with less agreement. Time required for classification was recorded to give an indication on its usability. One hundred digital cases were classified twice with a minimal 1-month time interval, with the use of the 2020 version of the OMT. Two pediatric hand surgeons, 2 rehabilitation specialists, and 2 plastic surgery residents participated in this reliability analysis. The use of multiple codes was allowed. The intra- and interrater reliability was assessed for all 15 possible rater couples by calculating percentage of agreement. Cohen's kappa was calculated along with a 95% confidence interval. For the analysis of individual codes with less agreement, we calculated positive agreement with the use of a summed agreement table. Time necessary for classification was documented in seconds. The inter- and intrarater agreement was moderate with a mean Cohen's kappa of 0.45 and 0.60 retrospectively. On average, 39 seconds per case were necessary for the first and 24 seconds for the second rating. Background did not influence the level of agreement. Lowest agreement levels (ie, lowest positive agreement) were observed with all the arthrogryposis multiplex congenita subgroups, the "other" subgroups of isolated congenital contractures, syndromic syndactyly, and synpolydactyly. Codes commonly used interchangeably were symbrachydactyly and transverse deficiency and the distinction between these anomalies of only the hand or the entire upper limb; symbrachydactyly and brachydactyly; and camptodactyly and distal arthrogryposis. Our study showed a moderate reliability, emphasizing the complexity of this heterogeneous patient population. Despite its imperfections, the OMT remains the best and most versatile classification tool at hand. Its main purpose may lie in contributing to a universal language for research. I.

Syndactyly is the most common congenital malformation of the hand, leading to the fusion of the digits and frequently affecting the ring and middle fingers. The incidence is 1 out of 2500 children, predominantly occurring in boys and Caucasians. Clinically, the malformation may present as a soft tissue or bony fusion, resulting in the union of the fingers characterised as complete or incomplete. This fusion may involve the phalanges but may also extend to the carpal/tarsal bones, even to the metacarpal or metatarsal level, rarely to the distal end of the forearm and lower leg. The malformation is mostly isolated but may occur together with other disorders or malformations such as synostosis, acro-syndactyly, cleft hand, clinodactyly, or polydactyly. Syndromic syndactyly can be observed in cases of Apert syndrome, Poland's syndrome, Pfeiffer syndrome, and many others. A girl born in June of 2019 was diagnosed with congenital malformation of the right hand at birth-affecting the right middle, ring, and little fingers, respectively. After X-ray imaging, the fusion of the third and fourth proximal phalanges to a common metacarpal was identified, forming a unique diagnosis of clino-syndactyly with metacarpal aplasia. Surgical intervention was advocated for, including a wedge osteotomy to correct the synchondrosis at the phalangeal base and a dorsal flap to close the interdigital space created during the correction of the III and IV. fingers. A trapezoid flap for the release of the syndactyly of the IV and V. fingers was applied. The paper aims to present this surgical correction and its results regarding an atypical case of syndactyly with clinodactyly and metacarpal aplasia.

A deletion of the distal long arm of chromosome 15 is generally reported with the formation of ring chromosome 15, whereas an isolated 15q deletion is rarely described. Here we report an 11 year-old girl, from non-consanguineous parents, who was referred to the Pediatric Genetics Department with growth retardation and multiple congenital abnormalities. In her medical history, she had a cleft palate, hip dislocation and crossed renal ectopia. Dysmorphological evaluation revealed a triangular face, low-set ears, fissured cleft tongue, micrognathia, proximally placed hypoplastic thumbs, genu valgus, 2-3 toe skin syndactyly, clinodactyly and nail hypoplasia. Speech problems were also noticed. The karyotype was normal. Subtelomeric fluorescent in-situ hybridisation (FISH) analysis showed a de novo terminal deletion about 755 kb. Furthermore, the breakpoint was located within the CHSY1 gene that is responsible for Temtamy preaxial brachydactyly syndrome which shares clinical features with 15qter deletion syndrome. To the best of our knowledge, this deletion is the smallest among reported patients. It is considered that the patient presented here significant contribution to phenotype-genotype correlation in 15q deletion patients.