Small supernumerary marker chromosomes (sSMCs) derived from the chromosome 6 short arm are rare and their clinical significance remains unknown. No case with sSMC(6) without centromeric DNA has been reported. Partial trisomy and tetrasomy of distal 6p is a rare but clinically distinct syndrome. We report on a de novo mosaic sSMC causing partial tetrasomy for 6p23-p25.3 in a male infant with symptoms of being small for gestational age, microcephaly, facial dysmorphism, congenital eye defects, and multi-system malformation. Conventional cytogenetic analysis revealed a karyotype of 47,XY,+mar [25]/46,XY [22]. Array comparative genomic hybridization (aCGH) revealed mosaic tetrasomy of distal 6p. This is the first case of mosaic tetrasomy 6p23-p25.3 caused by an inverted duplicated neocentric sSMC with characteristic features of trisomy distal 6p. Comparison of phenotypes in cases with trisomy and tetrasomy of 6p23-p25.3 could facilitate a genotype–phenotype correlation and identification of candidate genes contributing to their presentation. The presentation of anterior segment dysgenesis and anomaly of the renal system suggest triplosensitivity of the FOXC1 gene. In patients with microcephaly growth retardation, and malformation of the cardiac and renal systems, presentation of anterior segment dysgenesis might be indicative of chromosome 6p duplication, and aCGH evaluation should be performed for associated syndromic disease.

Williams syndrome (WS) is a rare genetic disorder caused by the microdeletion of chromosome 7q11.23. Cardiovascular defects (CVDs) are the leading causes of morbidity and mortality in patients with WS. The most common CVD in patients with WS is supravalvular aortic stenosis (SVAS), which recovers spontaneously similar to branch pulmonary stenosis (PS). Recently, conventional beliefs, such as SVAS improving rather than worsening in WS, have been challenged. This study thoroughly reviews the medical records of 30 patients with a molecular diagnosis of WS. We followed up these patients at Taipei MacKay Memorial Hospital from January 1999 to December 2021. The long-term outcomes of cardiovascular lesions as well as the change in peak pressure gradient in obstructive cardiovascular lesions over time were studied. Among these 30 patients, the most common cardiovascular lesion was SVAS (50.0%), followed by branch PS (36.7%). During the follow-up period, severe SVAS was aggravated (p = 0.021). The peak pressure gradient decreased from 38.4 to 25.3 mmHg (p = 0.001) in patients with branch PS. Among patients with WS, those with severe SVAS deteriorated over time, whereas those with branch PS improved on their own. In patients with WS who presented with branch PS, no disease-specific intervention was needed.

Costello syndrome (CS) is a type of RASopathy caused mainly by de-novo heterozygous pathogenic variants in the HRAS gene located on chromosome 11p15.5. The phenotype of CS is characterized by prenatal overgrowth, postnatal failure to thrive, curly or sparse fine hair, coarse facial features, and multisystem involvement, including cardiovascular, endocrine, and gastroenterological disorders. We present a one-year-old girl with rapid weight loss and severe failure to thrive. She had gastroesophageal reflux at the age of four months with subsequent rapid weight loss. The loss of fat tissue over the whole body, refractory to a hypercaloric diet, mimicked the presentation of progressive lipodystrophy and masked the dysmorphic features of CS. The final diagnosis of CS was made by whole exome sequencing, which demonstrated a hot-spot, heterozygouspathogenic variant in the HRAS gene (c.34G > A, rs104894229). Our patient illustrates that the excessive energy needs in CS patients may lead to severe failure to thrive and cause challenges in diagnosing CS. This case also highlights the importance of recognizing CS in patients with a history of prenatal overgrowth, polyhydramnios presenting with severe failure to thrive refractory to pharmacotherapy and tube feeding.