Genetic microcephaly includes
multiple syndromes that usually have normal chromosomal
studies but are presumed to have a genetic origin on the basis of a positive
family history, or proven to have a genetic origin on the basis of DNA
testing. Some patients considered to have genetic microcephaly may show
chromosomal abnormalities when prometaphase chromosome studies are performed.
Nevertheless, these patients are still classified as having a genetic
microcephaly because a normal prometaphase chromosomal study does not
exclude their diagnosis. When a genetic syndrome is diagnosed, the family
should be referred to a geneticist for counseling. The following are the
most common genetic syndromes.
with Brachmann-de Lange syndrome have typical facies. They are microcephalic,
with bushy eyebrows and synophrys, long curly eyelashes, depressed nasal
bridge, upturned nose, long philtrum, thin upper lip, and down-turned
angle of the mouth. In addition to characteristic facial features, neonates
with Brachmann-de Lange syndrome may have flexion contracture of the elbows,
hypoplastic nipples and umbilicus, low-set thumb, brachydactyly or syndactyly
of the second and third toes, hallux valgus, and sometimes absence of
the third toe. Prometaphase chromosome studies
should be done in all neonates with Brachman-de Lange syndrome. A duplication
of the q26-q27 band region of chromosome 3 is present in some patients
with Brachman-de Lange syndrome.
of Williams syndrome is based on the typical facies and cardiac abnormalities.
The facies is characterized by prominent lips and subcutaneous tissue
around the eyes. The irises are often blue and have a stellate pattern.
Neonates with Williams syndrome may also present with cardiac abnormalities
with or without the characteristic facies. The cardiac abnormalities include
supravalvular aortic stenosis, valvular aortic stenosis, aortic stenosis,
coarctation of the aorta, and pulmonary stenosis. Musculoskeletal malformations,
including arthrogryposis, may occur. Hypercalcemia is usually present.
The diagnosis may be established by fluorescent in situ hybridization
studies. Inherited and sporadic cases show deletion of chromosome subunit
7q11.23.5. Most cases are sporadic. Williams syndrome is a connective
tissue disorder. The 7q11 site constitutes the elastin gene.