SCIENTIFIC BACKGROUND

ADAMTS10, ADAMTS17, ADAMTSL2, ADAMTSL4, EFEMP1, FBN1, FBN2, LTBP2, LTBP3, MED12, SKI, UPF3B, ZDHHC9

Scientific Background

Marfan-like disorders comprise a group of syndromes with phenotypic overlaps with classic Marfan syndrome. These disorders include ectopia lentis syndrome, Shprintzen-Goldberg syndrome, congenital contractural arachnodactyly, Lujan-Fryns syndrome, geleophysial dysplasia and Weill-Marchesani syndrome. These syndromes can be caused by variants in different genes and show a variety of clinical features.

 

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 hypotonia 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 hypotonia 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

GENES

ADAMTS10, ADAMTS17, ADAMTSL2, ADAMTSL4, EFEMP1, FBN1, FBN2, LTBP2, LTBP3, MED12, SKI, UPF3B, ZDHHC9
How to order

LATEST ARTICLES

We're thrilled to share the results of Medicover Genetics essay competition for high school students as well as the two winning essays. This competit...

Read more

Cystic fibrosis (CF) is a life-threatening, progressive, inherited condition that causes severe damage to the body, primarily affecting the organs of...

Read more

Down syndrome is a genetic condition caused by the presence of an extra copy of chromosome 21. It affects physical growth, facial features, and cogni...

Read more

Every year on April 25th, DNA Day celebrates the discovery of DNA’s double helix and the advances we’ve made in understanding genetics. D...

Read more

Neurodevelopmental disorders (NDDs) have diverse genetic origins, making diagnosis challenging. A new study analyzing over 1,100 pediatric patients f...

Read more

Colorectal cancer (CRC) remains one of the most prevalent and deadly cancers worldwide, with a significant number of cases presenting at an advanced ...

Read more

Carrier screening is a genetic test designed to identify whether an individual carries a gene with changes (mutations) associated with inherited diso...

Read more

Trisomy 13, also known as Patau syndrome, is a genetic condition in which cells in the body have three copies of chromosome 13 instead of two. The co...

Read more

The human brain develops through a complex series of events, with genes carefully regulating the formation of neurons and glial cells. A recent study...

Read more

Rare diseases affect between 300 and 400 million people worldwide – more than cancer and AIDS combined [1, 2], but despite this, many people face a...

Read more