CHARGE syndrome is a rare autosomal dominant syndrome characterized by multiple congenital anomalies including coloboma, heart defects, ear anomalies, and developmental delay, caused by pathogenic variants in the CHD7 gene. The discovery of the molecular basis of this syndrome increased the number of cases reported and expanded the phenotype and clinical variability. Limb anomalies are occasional clinical findings in this syndrome, present in about 30% of reported cases. The occurrence of limb anomalies in this syndrome suggests that it should be considered as part of the phenotypic spectrum. Here, we describe an individual with CHARGE syndrome presenting unilateral monodactyly.

Polymelia is an extremely rare congenital anomaly where an individual is born with an abnormally developed extra or supernumerary limb which is generally shrunken and functionless. A case of thoracomelia (a type of polymelia) was observed macroscopically and confirmed radiologically in 1.5 years old boy born in Nepal with an abnormal supernumerary upper limb attached to his back in the thoracic region. The limb was successfully amputated, and the boy had a favorable outcome after surgical treatment, without any adverse effects or impairment. Understanding the embryogenesis of thoracomelia is essential for unraveling the complex mechanisms underlying this condition and potentially aiding in early diagnosis and intervention. This case report and review aims to shed light on the intricate processes governing forelimb formation and their perturbations leading to thoracomelia.

BACKGROUND: Orthopedic technical care plays a crucial role in improving function and mobility for patients undergoing limb lengthening and reconstruction. The treatment strategy is based on a precise classification of the defect, taking into account factors such as joint instability, muscle pathology and limb length discrepancy.
UNASSIGNED: The selection of orthopedic aids depends on the specific deformity, its classification and the individual needs of the patient. Through interdisciplinary decision-making and customized adaptations of prostheses and orthoses, optimal function and aesthetically pleasing outcomes can be achieved. The utilization of custom-made technical components, such as traction devices combined with elastic liners, is essential for long-term treatment success and can support surgical interventions. The treating physician\'s expertise is crucial in selecting the appropriate orthopedic technical device following limb lengthening and reconstruction.
UNASSIGNED: HINTERGRUND: Die orthopädietechnische Versorgung von Patienten mit Extremitätenverlängerung und -rekonstruktion spielt eine entscheidende Rolle für die Verbesserung der Funktion und Mobilität. Die Behandlungsstrategie basiert auf einer präzisen Klassifizierung des Defekts und berücksichtigt Faktoren wie Instabilität der Gelenke, Muskelpathologie und Beinlängendefizite. WAHL DER MAßNAHMEN: Die Wahl der orthoprothetischen Maßnahmen erfolgt in Abhängigkeit von der Fehlbildung, ihrer Klassifikation und der individuellen Ansprüche des Patienten. Durch eine interdisziplinäre Entscheidungsfindung und individuelle Anpassungen der Orthoprothesen kann eine optimale Funktion und ein ästhetisch ansprechendes Ergebnis erreicht werden. Die Verwendung von Orthoprothesen mit individuell gefertigten Bauteilen wie Traktionsvorrichtungen in Kombination mit elastischen Linern kann den langfristigen Behandlungserfolg überhaupt erst ermöglichen und chirurgische Eingriffe unterstützen. Eine gute Kenntnis des behandelnden Arztes ist entscheidend für die richtige Wahl der orthopädietechnischen Versorgung nach Extremitätenverlängerung und -rekonstruktion.

Introduction Some children with motor disabilities show low cognitive levels. However, the influence of motor disabilities on children\'s intelligence remains to be fully elucidated. This study aimed to clarify the intellectual characteristics of children with upper limb deficiencies and the influence of upper limb impairments on intelligence. Methods The participants were 10 children from four to six years of age with congenital unilateral transradial or transcarpal limb deficiencies who received prosthetic interventions. The children\'s intelligence and adaptive behaviors, including motor skills, were examined using the Wechsler Preschool and Primary Scale of Intelligence and the Vineland Adaptive Behavior Scale, respectively. Results There were no significant characteristics or discrepancies in cognitive level in children with upper limb deficiencies. The Adaptive Behavior Composite Score of the Vineland Adaptive Behavior Scale was significantly positively correlated with the Full-Scale Intelligence Quotient of the Wechsler Preschool and Primary Scale of Intelligence. Conclusions The children with congenital limb deficiencies showed average cognitive levels. Expansion of adaptive behaviors, including appropriate complementation of disabilities, may promote intellectual development in children with motor disabilities.

BACKGROUND: Triphalangeal thumb-polysyndactyly syndrome (TPT-PS) is a rare type of congenital limb deformity, and most studies focus on the genetics. Case reports of the sonographic characteristics of TPT-PS during pregnancy are rare.
METHODS: A 30-year-old woman (G3P1) who had pregnancies with TPT-PS fetuses is presented. The possibility of TPT-PS was shown by ultrasound performed at the 19th wk of pregnancy, featuring hands with six metacarpals, an extra digit at the 5th finger side, and an abnormally widened thumb. Whole-exome sequencing was subsequently conducted. The results showed that exons 1-17 of the LMBR1 gene had a heterozygous duplication, with a length of approximately 253 kb.
CONCLUSIONS: We suggest prenatal ultrasound examination combined with genetic testing to diagnose TPT-PS accurately and to help clinicians and patients make decisions.

Treacher Collins syndrome (TCS) is a congenital malformation of the craniofacial structures derived from the first and second pharyngeal arches. The craniofacial deformities are well described in the literature. However, little is known about whether there are associated extracraniofacial anomalies. A retrospective study was conducted using data from four craniofacial units. Medical charts were reviewed for the presence and type of extracraniofacial anomalies, as well as age at diagnosis. A possible correlation between the severity of the phenotype and the presence of extracraniofacial anomalies was assessed using the Hayashi classification. A total of 248 patients with TCS were identified; 240 were confirmed to have TCS, of whom 61 (25.4%) were diagnosed with one or more extracraniofacial anomalies. Ninety-five different extracraniofacial anomalies were found; vertebral (n=32) and cardiac (n=13) anomalies were most frequently seen, followed by reproductive system (n=11), central nervous system (n=7), and limb (n=7) anomalies. No correlations between tracts were found. Extracraniofacial anomalies were more prevalent in these patients with TCS compared to the general population (25.4% vs 0.001-2%, respectively). Furthermore, a positive trend was seen between the severity of the syndrome and the presence of extracraniofacial anomalies. A full clinical examination should be performed on any new TCS patient to detect any extracraniofacial anomalies on first encounter with the craniofacial team.

During the fifth century BC in ancient Greece during the eve of orthopaedics, the Hippocratic School of Medicine diagnosed a series of congenital limb deformities. Congenital dislocation of the arm, elbow, wrist, hip, knee, tarsotibial joint, apex leg, as well as talipes valgus (clubfoot), congenital clavicle fractures, and thumb malfunction were all discussed by Hippocrates and his followers. Ancient Greek medico-philosophers, fond of a \"perfect\" human body, proposed an immediate non-interventional approach, while archaic orthotics and specialized footwear were suggested. The Hippocratic methodology was once more re-emerged in the sixteenth century by Ambroise Paré and in the nineteenth century by Wilhelm Roser, becoming since then the main principle for the confrontation of congenital deformities. Various surgeons until nowadays are still being influenced by the Hippocratic doctrine.

Despite being a rare congenital limb anomaly, triphalangeal thumb is a subject of research in various scientific fields, providing new insights in clinical research and evolutionary biology. The findings of triphalangeal thumb can be predictive for other congenital anomalies as part of an underlying syndrome. Furthermore, triphalangeal thumb is still being used as a model in molecular genetics to study gene regulation by long-range regulatory elements. We present a review that summarizes a number of scientifically relevant topics that involve the triphalangeal thumb phenotype. Future initiatives involving multidisciplinary teams collaborating in the field of triphalangeal thumb research can lead to a better understanding of the pathogenesis and molecular mechanisms of this condition as well as other congenital upper limb anomalies.

The zone of polarizing activity regulatory sequence (ZRS) is an enhancer that regulates sonic hedgehog during embryonic limb development. Recently, mutations in a noncoding evolutionary conserved sequence 500 bp upstream of the ZRS, termed the pre-ZRS (pZRS), have been associated with polydactyly in dogs and humans. Here, we report the first case of triphalangeal thumb-polysyndactyly syndrome (TPT-PS) to be associated with mutations in this region and show via mouse enhancer assays how this mutation leads to ectopic expression throughout the developing limb bud.
We used linkage analysis, whole-exome sequencing, Sanger sequencing, fluorescence in situ hybridization, multiplex ligation-dependent probe amplification, single-nucleotide polymorphism array, and a mouse transgenic enhancer assay.
Ten members of a TPT-PS family were included in this study. The mutation was linked to chromosome 7q36 (LOD score 3.0). No aberrations in the ZRS could be identified. A point mutation in the pZRS (chr7:156585476G>C; GRCh37/hg19) was detected in all affected family members. Functional characterization using a mouse transgenic enhancer essay showed extended ectopic expression dispersed throughout the entire limb bud (E11.5).
Our work describes the first mutation in the pZRS to be associated with TPT-PS and provides functional evidence that this mutation leads to ectopic expression of this enhancer within the developing limb.

Developmental macular disorders are a heterogeneous group of rare retinal conditions that can cause significant visual impairment from childhood. Among these disorders, autosomal dominant North Carolina macular dystrophy (NCMD) has been mapped to 6q16 (MCDR1) with recent support for a non-coding disease mechanism of PRDM13. A second locus on 5p15-5p13 (MCDR3) has been implicated in a similar phenotype, but the disease-causing mechanism still remains unknown.
Two families affected by a dominant developmental macular disorder that closely resembles NCMD in association with digit abnormalities were included in the study. Family members with available DNA were genotyped using the Affymetrix GeneChip Human Mapping 250K Sty array. A parametric multipoint linkage analysis assuming a fully penetrant dominant model was performed using MERLIN. Haplotype sharing analysis was carried out using the non-parametric Homozygosity Haplotype method. Whole-exome sequencing was conducted on selected affected individuals.
Linkage analysis excluded MCDR1 from the candidate regions (LOD < -2). There was suggestive linkage (LOD = 2.7) at two loci, including 9p24.1 and 5p15.32 that overlapped with MCDR3. The haplotype sharing analysis in one of the families revealed a 5 cM shared IBD segment at 5p15.32 (p value = 0.004). Whole-exome sequencing did not provide conclusive evidence for disease-causing alleles.
These findings do not exclude that this phenotype may be allelic with NCMD MCDR3 at 5p15 and leave the possibility of a non-coding disease mechanism, in keeping with recent findings on 6q16. Further studies, including whole-genome sequencing, may help elucidate the underlying genetic cause of this phenotype and shed light on macular development and function.