D.P.1.12 FSHD and Williams syndrome: The occurrence of two genetic disorders due to heterozygous DNA fragment deletions in the same patient

Abstract

muscular disorder, is associated with a decreased number of D4Z4 repeats on chromosome 4q35. The pathogenic mechanisms underlying FSHD are still unknown. We report a patient diagnosed with Saethre-Chotzen syndrome at birth. The patient passed four surgeries due to craneosynostosis. High resolution chromosome analyses and molecular biology studies detected a deletion of the gene TWIST1 (SCS) at 7p15-p21. At 9-years old she started walking on tip-toes and subsequently developed facial hypomimia progressive weakness of facial and scapuloperoneal muscles, hyperlordosis and scoliosis. She also presented myopia, isolated focal seizures and moderate mental retardation. CPK levels were increased 2-fold. Muscle biopsy was neurogenic and showed a few angulated atrophic non specific esterase positive denervated fibers and type 2 predominance. Clinical considerations suggested the additional diagnosis of FSHD. Molecular sizing of the tandem D4Z4 repeats at 4q35 showed the presence of a contracted D4Z4 allele having 8 units. To our knowledge, this is the first report of a child with the rare association of SCS and FSHD. The clinical phenotype was essential in order to perform both SCS and FSHD diagnoses.