Weill-Marchesani Syndrome 1
Patient Information
Characteristics
Background and History
This rare disorder (WMS) of connective tissue was described independently by physicians Georges Weill and Oswald Marchesani in the 1930s.
Clinical Correlations
The major features of this disorder are: short stature, short fingers and stiff joints, and an abnormally shaped lens of the eye. The latter is sometimes called microspherophakia because it is smaller than normal and more round. It is also abnormally mobile and sometimes dislocates. The latter characteristic sometimes leads to a specific type of glaucoma called pupillary block because it plugs the pupil thereby blocking the normal circulation of ocular fluids and raises the pressure in the eye. Some individuals have difficulty making a tight fist as the finger joints especially are stiff. It is not unusual for some patients to have problems with their heart valves as well.
Short stature and short, stiff fingers have been observed in carriers (having one mutant gene) of the autosomal recessive form of WMS.
Genetics
Inheritance
About 45% of cases are inherited in an autosomal recessive pattern which requires that both parents are carriers (unaffected although they may be short in stature and have stiff joints). About 39% of cases are inherited in an autosomal dominant pattern in which case the condition is passed directly from parent to child. The remainder may represent new mutations.
Pedigree
Autosomal dominant
Autosomal dominant disorders require only one mutation for the disease to be expressed. Since an affected parent has two chromosomes, only one of which has the mutant gene, parents can expect that half (50%) of their children will receive that one and inherit the disease. It is common for individuals that inherit the mutation, however, to not have evidence of the disease (nonpenetrance).
Autosomal dominant inheritance leads to a vertical pattern of transmission
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.
Diagnosis and Prognosis
The diagnosis is often made by an eye doctor based on extreme nearsightedness and the abnormally shaped lens. Life span is normal provided any cardiac defects are appropriately treated. The major clinical problem for most patients results from the abnormal lens and the occurrence of glaucoma. The latter requires life-long monitoring and appropriate treatment.
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