APA (Old Order Amish; Eastern Pennsylvania)

Inheritance: autosomal recessive
Genes: ADAMTS10

WM syndrome
WMS
Spherophakia-brachymorpha syndrome

Short stature
Spherophakia
Brachydactyly
Joint stiffness

Weill-Marchesani Syndrome

Clinical Characteristics

General description (for patients):   

Individuals are short in stature and have short fingers with stiffness of various joints, especially in the hands.  The lens in the eye is abnormally small and can spontaneously dislocate causing an acute glaucoma.  Some also have floppy heart valves, leading sometimes to prolapse of the mitral valve.

Medical description: 

This is an extremely rare disorder, unusual in the fact that there are two phenotypically similar disorders, one an autosomal recessive and one an autosomal dominant.  The common clinical characteristics short stature, microspherophakia, brachymorphia, especially of the fingers, and stiffness of joints.  Floppiness of the cardiac valves may be subtle but mitral valve insufficiency has been documented.  The small spherical lenses may spontaneously sublux into the anterior chamber (which may also occur following pharmacologic mydriasis) leading to acute glaucoma that requires urgent attention.  This disorder is also notable because it is one of the few conditions that can that can spontaneously lead to a chronic pupillary block glaucoma.  This disorder is also notable because it is one of the few conditions that can  The hypercurvature of the lens produces a marked lenticular myopia that is completely reversed following lensectomy.  The recessive disease may have radiologic changes with short, wide diaphyses, thick cortical bones, and epiphyseal deformities.

Genetics:

The autosomal recessive form is caused by a mutation (15 exon del) in the ADAMTS10 gene on chromosome 19 (19p13.2-p12.3).  The dominant form may result from a mutation in the FBN1 gene on chromosome 15 (15q21) that is allelic to the Marfan gene.

Treatment:

The most important therapeutic treatment is lensectomy when the lens luxates into the anterior chamber causing acute glaucoma.  It should also be considered on a prophylactic basis due to the high risk of chronic pupillary block glaucoma in the phakic condition.  Regular ophthalmologist evaluations are recommended for this reason as well as the risk of postoperative aphakic open angle glaucoma.

Prognosis:

The bone and joint changes are not handicapping and life span is normal.  Blindness can result from glaucoma.

Ancillary treatments and support:

Correction of myopia.

Specialists and specialty centers:

Ophthalmologist, Orthopedist.

References:

Dagoneau, N., Benoist-Lasselin, C., Huber, C., Faivre, L., Megarbane, A., Alwaid, A., Dollfus, H., Alembik, Y., Munnich, A., Legeai-Mallet, L., and Cormier-Daire, V.:  ADAMTS10 mutations in autosomal recessive Weill-Marchesani syndrome.  Am. J. Hum. Genet. 75: 801-806, 2004.  PubMed ID: 15368195

Faivre, L., Dollfus, H., Lyonnet, S., Alembik, Y., Megarbane, A., Samples, J., Gorlin, R.J., Alswaid, A., Feingold, J., Le Merrer, M., Munnich, A., and Cormier-Dair, V.: Clinical homogeneity and genetic heterogeneity in Weill-Marchesani syndrome.  Am. J. Med. Genet. 123A: 204-207, 2003.  PubMed ID: 11941487

Jensen, A.,D., Cross, H.E., and Paton, D.:  Ocular complications in the Weill-Marchesani syndrome.  Am. J. Ophth. 77: 261-267, 1974. PubMed ID: 4812097

Resources:

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