Description

Scientific Background

While heterozygous FBN1 variants are the cause of autosomal dominantly inherited ectopia lentis syndrome (ECTOL1), homozygous or combined heterozygous variants in the ADAMTS4 gene lead to autosomal recessively inherited isolated lens dislocation known as ectopia lentis syndrome 2 (ECTOL2). A differential diagnosis for classic Marfan syndrome (MFS) is Shprintzen-Goldberg syndrome (SGS) due to the phenotypic overlap of craniofacial, cardiovascular, skeletal and skin manifestations. Additional symptoms of mental retardation and skeletal muscle hypotension also occur. SGS is mainly caused by variants in the SKI gene. Congenital contractile arachnodactyly (CCA) is characterized by a Marfanoid habitus, arachnodactyly, joint contractures, kyphoscoliosis, muscle hypotonia, auricular dysplasia and aortic root enlargement. CCA is caused by variants in the FBN2 gene. With marfanoid habitus, craniofacial features, generalized muscle hypotension and behavioral problems, Lujan-Fryns syndrome, also known as X-linked mental retardation (XLMR) with marfanoid habitus, overlaps with both MFS and SGS. Inheritance is X-linked recessive with variants in the genes MED12, UPF3B and ZDHHC9.

References

Ahram et al. 2009, Am J Hum Genet 84:274 / Doyle et al. 2012, Nature Genet 44:1249 / Schwartz et al. 2007, J Med Genet 44: 472