tall stature

Marfan Lipodystrophy Syndrome

Clinical Characteristics
Ocular Features: 

The eyes are large resulting in high myopia and apparent proptosis.  The palpebral fissures usually slant downwards and ectopia lentis may be present.  

Systemic Features: 

This syndrome shares many features of Marfan syndrome (154700) such as tall stature, dislocated lenses, myopia, high arched palate, aortic root and valvular anomalies, arachnodactyly, high arched palate, lax and hyperextensible joints, and pectus excavatum.  In addition, MFLS patients have retrognathia, intrauterine growth retardation, scarce or absent subcutaneous fat, a progeroid facies, and sometimes macrocephaly.  Postnatal growth and psychomotor development have been reported to be normal albeit with slow weight gain.

Genetics

This condition is transmitted as an autosomal dominant as the result of heterozygous mutations in FBN1 (15q21.1).  The same gene is mutated in 6 other conditions in this database including Marfan Syndrome (154700) with which it shares some features.

Pedigree: 
Autosomal dominant
Treatment
Treatment Options: 

There is no treatment for the overall condition but individual features such as ectopia lentis can be surgically corrected.  Patients with high myopia require frequent evaluation for retinal tears and detachments.  Cardiac monitoring likewise is important to monitor for aortic valve prolapse and dilation of the aortic root.

References
Article Title: 

Marfan Syndrome

Clinical Characteristics
Ocular Features: 

Marfan syndrome typically has skeletal, ocular and cardiovascular abnormalities.  The globe is elongated creating an axial myopia and increasing the risk of rhegmatogenous retinal detachments.  Ectopia lentis is, of course, the classical ocular feature and is often if not always congenital with some progression.  The lenses most frequently dislocate superiorly and temporally and dilating the pupils often reveals broken and retracted lens zonules.  Phacodenesis and iridodenesis are commonly present even in the absence of evident lens dislocations. Cataracts develop several decades earlier than in unaffected individuals. The cornea is generally several diopters flatter than normal and there is an increased risk of open angle glaucoma.  There is considerable clinical variation among patients.

Systemic Features: 

Patients with the Marfan phenotype are usually tall with disproportionately long limbs (dolichostenomelia) and digits (arachnodactyly).   Patients frequently have scoliosis or kyphoscoliosis.  The joints are lax and hyperflexible although contractures can also occur.  The sternum is often deformed, either as a pectus excavatum, or sometimes pectus carinatum.  The hard palate is high and narrow resulting in crowding of the teeth and maloccclusion.  The defect in fibrillin is responsible for the weakness in connective tissue that leads to frequent cardiac valve malfunction, especially insufficiency of the aortic valve resulting from aortic dilatation, tear, and rupture.  The latter is often life-threatening as aortic dissection can be fatal.  Mitral valve prolapse is seen as well.  Cardiovascular disease is primarily responsible for the shortened life expectancy in this disease, more pronounced among males.

Genetics

As many as 25% of cases are caused by new mutations, but familial cases usually follow an autosomal dominant pattern of inheritance.  Autosomal recessive inheritance is claimed for several individuals in a consanguineous Turkish family.  Mutations in the fibrillin-1 gene (FBN1) on chromosome 15 (15q21.1) are considered responsible for the typical phenotype.  The exact nature of the fibrillin defect is unknown but the result is a generalized weakness in connective tissue.

The same gene is mutant in the autosomal dominant form of the Weill-Marchesani syndrome (608328) which is allelic to the Marfan syndrome.

Mutations in FBN1 have also been found in cases with isolated autosomal dominant ectopia lentis (129600).

Pedigree: 
Autosomal dominant
Treatment
Treatment Options: 

Isometric exercises such as weight lifting should be avoided as should contact sports in which blunt trauma to the chest may occur because of the weakened aortic wall due to cystic changes that predispose the athlete to aortic dissection.  A dislocated and/or cataractous lens may need to be removed from the visual axis, and, of course, periodic retinal examinations for retinal holes and retinal detachments should be made.   Beta-adrenergic blockade reduces the risk of aortic dilatation and improves survival.

Pravastatin has been reported to reduce aortic dilation in marfan mice.

References
Article Title: 

Pravastatin reduces marfan aortic dilation

McLoughlin D, McGuinness J, Byrne J, Terzo E, Huuskonen V, McAllister H, Black A, Kearney S, Kay E, Hill AD, Dietz HC, Redmond JM. Pravastatin reduces marfan aortic dilation. Circulation. 2011 Sep 13;124(11 Suppl):S168-73.

PubMed ID: 
21911808
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