Holt-Oram syndrome, also known as atrio-digital syndrome, is a rare autosomal dominant genetic disorder primarily characterized by upper limb malformations and congenital heart defects, associated with mutations in the TBX5 gene. Diagnosis is typically based on clinical presentation, and the prognosis for affected individuals is closely related to the severity of cardiac involvement. Our study aims to highlight some key features of Holt-Oram syndrome to improve the level of clinical diagnosis. We collected 11 patients with clinical features strongly suggestive of Holt-Oram Syndrome at the First Affiliated Hospital of Tsinghua University from January 2010 to January 2025. These patients exhibited both limb malformations and cardiac abnormalities. We then analyzed the characteristics of their diseases. The skeletal abnormalities and cardiac defects presented in diverse forms among the 11 patients. Among the congenital heart diseases, atrial septal defect (ASD) was the most common, accounting for 80% of cases. However, some patients presented with severe conditions such as tetralogy of Fallot or Ebstein's anomaly. Regarding upper limb malformations, the most frequent finding was triphalangeal thumb (8/10 patients), but thumb hypoplasia or aplasia and radial bone abnormalities were also observed. The predominant cardiac structural abnormality in this group of patients was atrial septal defect. Upper limb malformations were predominantly characterized by polydactyly or syndactyly. However, arrhythmias appeared to be mainly supraventricular tachycardia, and upper limb involvement did not seem to show a clear left-sided predominance. The prognosis following cardiac corrective surgery was favorable. Nevertheless, for this condition, emphasis should be placed on prevention.

We report a case of a rare type of polydactyly associated with VACTERL association (verebral defects, anal atresia, cardiac defects, tracheo-esophageal fistula,renal anomalies, and limb abnormalities) that was treated surgically in infancy with good results. In this case, the patient had radial and ulnar thumbs of almost equal size, and mild thumb hypoplasia. This thumb is as classified Blauth type Ⅰ thumb hypoplasia and as a type IV triphalangeal thumb in the Rotterdam classification. The radial thumb had one phalanx with no distal phalanx or nail plate, whereas the ulnar thumb had three phalanges, including a distal phalanx and nail plate. On-top plasty was performed, joining the ulnar thumb top to the radial thumb base. One year after surgery, the appearance of thumb is good, and the child can use the affected digit well in daily activities. However, flexion and extension of the interphalangeal joint of the thumb is weak. Follow-up will be continued to monitor growth of the reconstructed thumb.

In a series of 271 consecutive duplicated thumbs, an angular, hypertrophied epiphysis was detected in 13 thumbs. We propose a revised version of the radial polydactyly classification that includes this pattern as a separate type from triphalangeal thumb.

Genetic variants in the zone of polarizing activity regulatory sequence (ZRS) that induce ectopic expression of the SHH gene have been associated with different ZRS-related phenotypes. We report the first patient with a de novo variant, c.423+4916 T>C, in ZRS (previously classified as a variant of uncertain significance) that causes tibial hemimelia-polysyndactyly-triphalangeal thumb syndrome (THPTTS). A two-month-old male patient presented with bilateral preaxial polydactyly, triphalangeal thumb, and tibial agenesis and was heterozygous for the variant c.423+4916T>C (neither of his parents was a carrier). The findings obtained from the family study were sufficient to reclassify the variant from "uncertain significance" to "likely pathogenic" according to three criteria from the American College of Medical Genetics and Genomics guidelines, as follows: (1) absence of gnomAD, (2) confirmation of paternity and maternity, and (3) strong phenotype-genotype association. In ZRS-associated syndromes, a wide clinical spectrum has been observed, ranging from polydactyly to THPTTS; our patient has the most severe and rare phenotype. We did not perform functional assays. However, the c.423+4916T>C variant is flanked by three variants, which have been proven not only to cause the phenotype but also to increase the expression of SHH. Through all this data gathering, we consider the c.423+4916T>C variant to be causative of THPTTS.

In this report, we present the combination of on-top plasty with a modified Bilhaut-Cloquet procedure for treating atypical radial polydactyly with duplication at the metacarpophalangeal (MP) joint and triphalangism of the radial and ulnar phalanges, hypoplastic middle phalanx of the radial thumb, and hypoplastic phalanx base of the ulnar thumb. To preserve the stable MP and interphalangeal joints of the radial and ulnar thumbs, respectively, on-top plasty involved osteotomizing the middle phalanx and transferring the distal end of the middle phalanx of the ulnar finger to the phalanx base of the radial thumb. A modified Bilhaut-Cloquet procedure was used to combine the tips and nails of both thumbs. Twelve months postoperatively, good joint alignment and thumb tip appearance were achieved. On-top plasties effectively combined the desirable parts of both thumbs. The modified Bilhaut-Cloquet technique is particularly well-suited for atypical cases, such as the present case.