Simpson-Golabi-Behmel syndrome

Simpson–Golabi–Behmel syndrome
Simpson–Golabi–Behmel syndrome has an X-linked recessive pattern of inheritance.
Classification and external resources
Specialty	medical genetics
ICD-10	Q87.3
ICD-9-CM	759.89
OMIM	312870
DiseasesDB	32640
Orphanet	373
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Simpson–Golabi–Behmel syndrome (SGBS), also called Bulldog syndrome, Sara Agers syndrome, Golabi–Rosen syndrome, Simpson dysmorphia syndrome (SDYS) or X-linked dysplasia gigantism syndrome (DGSX), is a rare inherited congenital disorder that can cause craniofacial, skeletal, cardiac, and renal abnormalities. The syndrome is inherited in an X-linked recessive fashion, where males express the phenotype and females usually do not. Females that possess one copy of the mutation are considered to be carriers of the syndrome and may express varying degrees of the phenotype.

Although not all causes of SGBS have been identified, one cause of SGBS type I is a mutation of the glypican-3 gene (GPC3) on the X chromosome locus q26.1. This particular gene is widely expressed, especially in tissues derived from the mesoderm during fetal development. The function of this gene is to produce a protein that acts as a cell surface receptor that binds to transcription factors. Binding of the transcription factors allows regulation of cellular responses to growth factors such as members of the hedgehog protein family. When large or small deletions and missense mutations occur along the GPC3 gene, GPC3 can no longer negatively regulate Hedgehog signaling during development, therefore increasing cell proliferation and the risk of developing cancer. Limb patterning and skeletal development may also go awry when GCP3 mutations inhibit regulations of responses to bone morphogenetic proteins, another type of growth factor.

It has been suggested that SGBS type II may be caused by duplication of the GPC4 gene, which helps to regulate cell division and growth.

Also, some patients diagnosed with SGBS do not have any GPC3 or GPC4 deletions or mutations. Possible explanations include promoter mutation or silencing of the GPC3 gene causing reduced expression in these patients.

The disorder is passed on in an X-linked recessive fashion.

Detection usually begins with a routine doctor visit when the fundal height is being measured or during an ultrasound examination. When large for gestational age fetuses (LGA) are identified, there are two common causes: maternal diabetes or incorrect dates. However, if these two causes can be ruled out, an ultrasound is performed to detect for overgrowth and other abnormalities. At this point, it becomes essential for a clinical geneticist to assist in the correct selection of tests and possible diagnosis.

First signs of SGBS may be observed as early as 16 weeks of gestation. Aids to diagnosing might include the presence of macrosomia, polyhydramnios, elevated maternal serum-α-fetoprotein, cystic hygroma, hydrops fetalis, increased nuchal translucency, craniofacial abnormalities, visceromegaly, renal abnormalities, congenital diaphragmatic hernia, polydactyly, and a single umbilical artery.

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