LUJAN-FRYNS SYNDROME

Scientific background

Patients with Lujan-Fryns syndrome (LFS), also known as X-linked intellectual disability (XLMR) with marfanoid habitus or X-lined syndromic intellectual developmental disorder (MRXSLF), present with marfanoid habitus, certain craniofacial features, generalized muscle hypotonia, developmental delay, behavioral problems, and nasal speech. Thus, there is clinical overlap with other connective tissue disorders such as Marfan syndrome (MFS), Loeys-Dietz syndrome (LDS), and Shprintzen-Goldberg syndrome (SGS). Inheritance is X-linked recessive, resulting in predominantly male patients, while female carriers are usually clinically inconspicuous.

Hemizygous variants in the MED12 gene, which encodes mediator complex subunit 12, are the genetic cause. Allelic disorders with MED12 variants include FG syndrome type 1 (FGS1) and X‑linked Ohdo syndrome (XLOS). Subsequently, variants in the UPF3B and ZDHHC9 genes have also been described in patients with intellectual disability and marfanoid habitus. However, these patients only partially exhibited the characteristic facial abnormalities of LFS, such as a long narrow face, prominent forehead, broad nasal root, short philtrum, micrognathia, and high palate.

References

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