Rare Double Aneuploidy (Down-Klinefelter Syndrome): A Case Report.

Double aneuploidies, such as Down syndrome and sex chromosome aneuploidies, are relatively rare. One rare form of double aneuploidy, Down-Klinefelter syndrome, is described here. The phenotypic characteristics of a three-year-old child showed the presence of features typical of Down syndrome. He had a global developmental delay, small testes, and diabetes mellitus by 18 months of age. Regardless of the presenting clinical features, karyotyping should be performed in all patients with suspected Down syndrome. In Down-Klinefelter syndrome, anticipatory phenotype goes beyond the sum of individual syndromic characteristics.

Weill-Marchesani Syndrome, a Rare Presentation of Severe Short Stature with Review of the Literature.

BACKGROUND Short stature is the second most common reason for referral to a pediatric endocrinology clinic. Numerous genetic causes have been identified. Weill-Marchesani syndrome (WMS) is one of the rare genetic disorders that cause short stature. It is caused by homozygous mutations in the FBN1 gene, ADAMTS10 gene, ADAMTS17 gene, or LTBP2 gene. Despite genetic heterogeneity, WMS is clinically homogeneous. It is characterized by short stature, brachydactyly, joint stiffness, ocular abnormalities, mainly microspherophakia and glaucoma, and occasionally cardiac defects. CASE REPORT A 9-year-old boy had bilateral narrow-angle glaucoma with lens subluxation, elevated intraocular pressure, and severe myopia since early childhood. He had phenotypic dysmorphic features and radiological findings consistent with WMS. He underwent lensectomy and scleral-fixated intraocular lens implantation as well as drug treatment to control the intraocular pressure. He was a slow grower, and his growth parameters showed disproportionate short stature with brachydactyly and joint stiffness. Growth hormone provocation tests were subnormal with a peak value of 7.89 ng/mL. CONCLUSIONS The constellation of clinical presentation, radiological findings, and the molecular examination confirmed a homozygous familial variant of the ADAMTS10 gene identified by carrier gene testing. This known familial variant creates a premature termination codon classified as a likely pathogenic cause of WMS. In this syndrome, glaucoma treatment is considered the greatest challenge. The disease-causing mechanism in WMS is not known but thought to be due to abnormal actin distribution and organization in fibroblasts as a result of impaired connections between extracellular matrix components and the cytoskeleton.