OMIM ID:
Weill-Marchesani Syndrome 1
Alternate Names
Defective Genes
Clinical Characteristics
Ocular Features
The Weill-Marchesani phenotype is a rare connective tissue disorder manifested by short stature, brachydactyly, spherophakia and stiff joints. As many as 94% have spherophakia and 64% have dislocated lenses. The central corneal thickness is increased. The small, abnormally shaped lens can migrate anteriorly causing pupillary block glaucoma and sometimes dislocates into the anterior chamber. This may occur spontaneously or following pharmacologic mydriasis which is sometimes done to relieve the pupillary block.
Systemic Features
Short stature in the range of 155 cm in height for men and 145 cm for women is common. Brachydactyly and stiff joints prevent patients from making a tight fist. A few patients (13%) have some mild mental deficit but most have normal intelligence. Cardiac defects include patent ductus arteriosis, pulmonary stenosis, prolonged QT interval mitral valve stenosis, and mitral valve prolapse. Some heterozygous carriers also are short in stature and may have joint stiffness.
Genetics
Inheritance
Homozygous mutations in the ADAMTS10 gene (19p13.3-p13.2) cause this disorder. Homozygous mutations in LTBP2 (14q24.3) have also been found in WMS1 and in the Weill-Marchesani-Like syndrome (613195).
Weill-Marchesani syndrome 2 (608328) is a clinically similar syndrome but results from heterozygous mutations in FBN1. Homozygous mutations in ADAMTS17 cause the Weill-Marchesani-Like syndrome (613195) . It is not always possible to distinguish between the AR and AD forms of the disease using clinical criteria alone.
Pedigree
Autosomal recessive
In order for autosomal recessive disorders to be expressed, offspring generally must inherit two mutations, one from each carrier parent. Carriers with only one mutation, such as the parents, do not have clinical disease. Note that carrier parents can expect that 1 in 4 children (25%) will inherit both mutations and have the disorder, 2 in 4 children (50%) will be carriers like their parents, while 1 in 4 children (25%) inherit neither mutation.
In order for autosomal recessive disorders to be expressed, offspring generally must inherit two mutations, one from each carrier parent. Carriers with only one mutation, such as the parents, do not have clinical disease. Note that carrier parents can expect that 1 in 4 children (25%) will inherit both mutations and have the disorder, 2 in 4 children (50%) will be carriers like their parents, while 1 in 4 children (25%) inherit neither mutation.