RESUMEN
Dyggve-Melchior-Clausen dysplasia (DMC) and Smith-McCort dysplasia (SMC types 1 and 2) are rare spondylo-epi-metaphyseal dysplasias with identical radiological and clinical findings. DMC and SMC type 1 are allelic disorders caused by homozygous or compound heterozygous variants in DYM, while biallelic causative variants in RAB33B lead to SMC type 2. The terminology "skeletal golgipathies" has been recently used to describe these conditions, highlighting the pivotal role of these two genes in the organization and intracellular trafficking of the Golgi apparatus. In this study, we investigated 17 affected individuals (8 males, 9 females) from 10 unrelated consanguineous families, 10 diagnosed with DMC and seven with SMC type 2. The mean age at diagnosis was 9.61 ± 9.72 years, ranging from 20 months to 34 years, and the average height at diagnosis was 92.85 ± 15.50 cm. All patients exhibited variable degrees of short trunk with a barrel chest, protruding abdomen, hyperlordosis, and decreased joint mobility. A total of nine different biallelic variants were identified, with six being located in the DYM gene and the remaining three detected in RAB33B. Notably, five variants were classified as novel, four in the DYM gene and one in the RAB33B gene. This study aims to comprehensively assess clinical, radiological, and molecular findings along with the long-term follow-up findings in 17 patients with DMC and SMC type 2. Our results suggest that clinical symptoms of the disorder typically appear from infancy to early childhood. The central notches of the vertebral bodies were identified as early as 20 months and tended to become rectangular, particularly around 15 years of age. Pseudoepiphysis was observed in five patients; we believe this finding should be taken into consideration when evaluating hand radiographs in clinical assessments. Furthermore, our research contributes to an enhanced understanding of clinical and molecular aspects in these rare "skeletal golgipathies," expanding the mutational spectrum and offering insights into long-term disease outcomes.
RESUMEN
Copy number variations in subtelomeric regions of chromosomes 17 and 20 are associated with intellectual disability and various systemic manifestations. Microarray analysis allows identification of submicroscopic chromosomal abnormalities and is applicable to elucidate the etiology of cognitive impairment in approximately one-fifth of the cases. In the present study, we report on 3 male children from 2 sisters, who suffered from intellectual disability, facial dysmorphism, and epilepsy. Despite the initial suggestion of an X-linked inheritance, the condition was associated with 17q25.3 duplication and concomitant 20q13.33 deletion, as detected by microarray analysis. Coexistence of a deletion and a duplication suggests unbalanced segregation of a parental balanced translocation. Further investigations revealed maternal balanced translocations, which resulted in copy number aberrations in the children following unbalanced segregations. The work-up underlined the importance of genomic screening using microarrays as the first-tier diagnostic tool in intellectual disability, despite an apparent X-linked segregation in the pedigree.
