Camptodactyly-arthropathy-coxa vara-pericarditis (CACP) syndrome is a rare autosomal recessive disorder caused by PRG4 mutations that impair lubricin production. Resulting noninflammatory hyperplasia produces congenital or early-onset camptodactyly and noninflammatory arthropathy, affecting large joints. Because clinical features overlap with trigger finger and juvenile idiopathic arthritis (JIA), misdiagnosis is common. We describe the second genetically confirmed Brazilian case of CACP, involving two siblings. Both showed congenital trigger fingers (later reclassified as camptodactyly) and developed painless, cold swelling of large joints, initially labeled JIA. Laboratory tests showed normal inflammatory markers, and synovial fluid revealed low white cell counts. Imaging demonstrated joint effusion and synovial debris without inflammatory signs. Whole-genome sequencing identified a homozygous c.3756dup mutation in the PRG4 gene, introducing a premature stop codon and truncating lubricin. This report highlights the importance of recognizing CACP syndrome by identifying distinctive clinical, laboratory, and imaging characteristics, notably congenital camptodactyly and noninflammatory joint swelling, to prevent misdiagnosis and guide supportive management.

Fractional tendon lengthening (FTL) is a technique to release certain contractures of various musculotendinous units of the upper and lower limb. It is traditionally done as an open procedure in the operating room under varying types of anaesthesia. A 19-year-old female with an isolated middle finger flexor digitorum superficialis (FDS) contracture who underwent ultrasound-guided percutaneous FTL under wide awake local anaesthesia, without a tourniquet, is presented. This alternative FTL technique allows for a percutaneous approach, which can be done in the clinic under local anaesthesia with possibly comparable outcomes to the standard open approach. Level of Evidence: Level V (Therapeutic). FGD1-related faciogenital dysplasia (Aarskog-Scott syndrome) is characterized by distinctive craniofacial features (including broad forehead, widow's peak and/or frontal upsweep, hypertelorism, ptosis, short nose with a broad nasal bridge and anteverted nares, wide mouth, and rectangular thickening of the ear lobes), short stature, skeletal anomalies (including short/broad hands, brachydactyly, camptodactyly, "swan neck" finger deformities, prominent interphalangeal joints, and metatarsus varus), genital anomalies including shawl scrotum and cryptorchidism, dental anomalies, variable neurodevelopmental disorders, ophthalmologic findings, and inguinal hernia. Congenital malformations such as cardiac defects, central nervous system anomalies, and cleft lip and/or palate are less common. Heterozygous females are typically asymptomatic or show a milder, incomplete phenotype. The diagnosis of Aarskog-Scott syndrome is established in a male proband with characteristic clinical findings and a hemizygous FGD1 pathogenic variant identified by molecular genetic testing. The diagnosis of Aarskog-Scott syndrome can be established in a female proband with characteristic clinical findings (milder, incomplete phenotype) and a heterozygous FGD1 pathogenic variant identified by molecular genetic testing; Heterozygous females are typically asymptomatic. Treatment of manifestations: Growth hormone therapy may be considered in those with growth hormone deficiency or persistent growth deficiency in those born small for gestational age without catch-up growth; standard orthopedic management for camptodactyly, foot malposition, and osteochondritis; standard treatment for cryptorchidism; standard dental and orthodontic care; developmental and educational support; standard ophthalmologic management of vision issues; ptosis surgery if visual axis is obstructed; standard management of hernias and anorectal anomalies; standard treatment of congenital heart disease; surgical correction for cleft lip and palate; speech therapy when needed. Surveillance: Measurement of growth parameters at every visit until adulthood; clinical musculoskeletal examination annually or as needed; monitor testicular descent at each pediatric visit; dental evaluations beginning with tooth eruption then annually or as clinically indicated; monitor developmental progress, educational needs, and for attention-deficit/hyperactivity disorder at each visit; ophthalmology evaluation annually in childhood and adolescence or as clinically indicated; assess for inguinal hernia at each visit; follow-up echocardiography as indicated by cardiologist; follow up for cleft lip/palate as clinically indicated; audiology evaluation annually in childhood and adolescence or as clinically indicated. Agents/circumstances to avoid: Avoid movements that cause sudden stress to the head and neck (e.g., somersaults, head dives, high-force cervical manipulation) and neck hyperextension during procedures until cervical abnormalities have been ruled out. Obtain cervical spine radiographs before general anesthesia. Evaluation of relatives at risk: It is appropriate to clarify the genetic status of apparently asymptomatic older and younger at-risk male relatives of an affected individual in order to identify as early as possible those who would benefit from echocardiogram and management of congenital heart disease. Aarskog-Scott syndrome is inherited in an X-linked manner. About 10% of affected males have the disorder as the result of a de novo pathogenic variant. If the mother of the proband has an FGD1 pathogenic variant, the chance of the mother transmitting it in each pregnancy is 50%. Males who inherit the pathogenic variant will be affected. Females who inherit the pathogenic variant will be heterozygotes and will usually be asymptomatic or have a partial or milder phenotype. Affected males transmit the FGD1 pathogenic variant to all of their daughters and none of their sons. Once the FGD1 pathogenic variant has been identified in an affected family member, identification of female heterozygotes and prenatal/preimplantation genetic testing are possible.

ZC4H2 is an X-linked gene that has emerged as critical for neural development, synaptic functioning, and gene regulation. We present an 11-month-old male who was evaluated for bilateral congenital vertical talus identified in the newborn period. Exome sequencing identified a hemizygous, missense variant in ZC4H2, NM_018684.4:c.196C>T p.(Leu66Phe), that affects the same amino acid residue as a previously reported, pathogenic ZC4H2 variant, c.197T>A p.(Leu66His). The variant was inherited from his mother, who had camptodactyly of the fifth fingers, and was also present in the maternal uncle who carried a diagnosis of cerebral palsy. The pathogenic missense variant in this family is located in the coiled-coil domain of the ZC4H2 protein. Although data remain scarce, missense variants in this domain may be associated with a milder, ZC4H2-associated rare disorder (ZARD) phenotype.

Syndactyly is one of the most common congenital malformations of the hand/foot, characterized by varying degrees of soft tissue and/or skeletal fusion between adjacent fingers or toes. It may also occur alongside polydactyly, camptodactyly, brachydactyly, or congenital joint fusion. The heterogeneity in its clinical phenotypes and incomplete penetrance makes it challenging to establish clear diagnostic and treatment protocols/procedures. Conventionally, the management of syndactyly has mainly relied on clinical experience, with limited reference to cutting-edge genetic research and systematic treatment strategies. To standardize the diagnosis and treatment of syndactyly and update the treatment protocols, a consensus has been developed by experts from the Hand Plastic Surgery Committee of the Aesthetic and Plastic Surgeon Branch of Chinese Medical Doctor Association, Clinical Genetics Group of the Medical Geneticist Branch of Chinese Medical Doctor Association, Pediatric Plastic Surgery Group of Plastic Surgery Branch of Chinese Medical Association, and Assistive Devices Application Committee of the Chinese Rehabilitation Medicine Association, and leading universities and hospitals across China. This expert consensus, incorporating both clinical and genetic research, as well as recent international and domestic findings, aims to serve as a reference for clinicians. EZH2-related overgrowth is a variable overgrowth syndrome characterized by tall stature, macrocephaly, variable intellect (ranging from normal intellect to severe intellectual disability), characteristic facial appearance, and a range of associated clinical features including advanced bone age, poor coordination, soft, doughy skin, camptodactyly of the fingers and/or toes, umbilical hernia, abnormal tone, and hoarse, low cry in infancy. Brain MRI has identified abnormalities in a few individuals with EZH2-related overgrowth. Neuroblastoma occurs at an increased frequency in individuals with a heterozygous EZH2 pathogenic variant. There is currently no evidence that additional malignancies (including hematologic malignancies) occur with increased frequency, though a few have been reported. The diagnosis of EZH2-related overgrowth is based on detection of a heterozygous germline EZH2 pathogenic variant on molecular genetic testing. Treatment of manifestations: For individuals with developmental delay and/or learning disability, referral for learning/behavior/speech assessment and support may be indicated. Occasionally, toe camptodactyly may require surgical release. Physiotherapy may be of benefit to those experiencing joint pain secondary to ligamentous laxity or joint contractures. Standard treatment with appropriate specialist referral(s) is indicated for epilepsy, scoliosis, and other clinical issues. Surveillance: Regular medical follow up of young children with EZH2-related overgrowth to monitor developmental progress, camptodactyly (for resolution/improvement), and/or hypotonia; medical follow up of older children/teenagers who do not have medical complications may be less frequent. If scoliosis is present, monitoring per the recommendations of an orthopedist. Clinicians should have a low threshold for investigating any possible tumor-related symptoms. There are no internationally ratified surveillance guidelines for screening of neuroblastoma in individuals carrying inactivating EZH2 pathogenic variants, but US guidelines recommend imaging and urine biochemistry surveillance until age 10 years. Pregnancy management: Families and their health care providers should be made aware that an affected baby may be large so that appropriate delivery plans can be made. EZH2-related overgrowth is inherited in an autosomal dominant manner. Some individuals diagnosed with EZH2-related overgrowth have an affected parent; some individuals diagnosed with EZH2-related overgrowth have the disorder as the result of a de novo EZH2 pathogenic variant. The proportion of individuals with EZH2-related overgrowth caused by a de novo pathogenic variant is unknown. Each child of an individual with EZH2-related overgrowth has a 50% chance of inheriting the pathogenic variant; the phenotype in individuals who inherit a familial EZH2 pathogenic variant cannot be predicted. Once the pathogenic variant has been identified in an affected family member, prenatal and preimplantation genetic testing are possible.

This case report and literature review documents an ultra-rare de novo copy number gain at 5q14.3q15. The patient's phenotype included hypotonia, microcephaly, global developmental delay, iris hypoplasia, atrophy, sweat dysregulation, and skeletal implications, including camptodactyly. This case presentation provides novel insights into the genotype-phenotype correlation for 5q14.3q15 copy number gain, particularly highlighting the involvement of the MEF2C gene (#MIM 600662). Through comprehensive clinical and genetic evaluation, we aim to enhance the understanding of this ultra-rare genetic condition and its implications.