A Turkish family with Ellis-van Creveld syndrome in six siblings; linkage analysis on 4p16 region (D4S3360-D4S2366)

Area of Science:

• Genetics
• Pediatrics
• Medical Diagnostics

Background:

• Ellis-van Creveld (EVC) Syndrome is a rare genetic disorder characterized by skeletal abnormalities and congenital heart defects.
• Autosomal recessive inheritance is typical for EVC Syndrome, but specific genetic markers and phenotypic variations require further investigation.

Observation:

• A Turkish family with six consecutively affected children presented with features consistent with EVC Syndrome.
• Two affected siblings underwent detailed cardiologic evaluation, revealing ostium primum atrial septal defect, mitral cleft, partial abnormal pulmonary venous return, and pulmonary stenosis.

Findings:

• Linkage analysis using polymorphic markers D4S3360-D4S2366 at the 4p16 locus confirmed the diagnosis of EVC Syndrome.
• Complete segregation of disease and marker alleles, with affected siblings being homozygotes, supported autosomal recessive inheritance.
• Novel cardiac anomalies (partial abnormal pulmonary venous return, pulmonary stenosis) and distinct postaxial polydactyly (bifid metacarpal and phalanges) were observed.

Implications:

• Molecular analysis provides definitive diagnosis for EVC Syndrome, aiding in genetic counseling and family planning.
• The identification of previously unreported cardiac and limb phenotypes expands the understanding of EVC Syndrome's clinical spectrum.
• This study highlights the importance of comprehensive genetic and phenotypic evaluation in rare genetic disorders.