Introduction
Simpson-Golabi-Behmel syndrome (SGBS) is a rare condition with various congenital anomalies, pre or postnatal overgrowth, specific craniofacial traits, macrocephaly, and organomegaly. It was first described in 1975 by Joe Leigh Simpson and colleagues. Skeletal, cardiovascular, central nervous system, renal, and gastrointestinal tract abnormalities are also possible. Intellectual disability, speech delay, and early motor milestones are occasionally observed; however, a significant number of people have normal intelligence.
Simpson-Golabi-Behmel syndrome (SGBS) is also linked to an increased chance of developing embryonal cancers, most notably Wilms and liver tumors. So far, about 250 people have been identified with this condition; however, the incidence of Simpson-Golabi-Behmel syndrome is unknown. Golabi-Rosen syndrome, Simpson dysmorphia syndrome (SDYS), or X-linked dysplasia gigantism syndrome (DGSX) are the other names for this condition.
What Is Simpson-Golabi-Behmel Syndrome?
Simpson-Golabi-Behmel syndrome is a disorder that mostly affects men. This is an overgrowth syndrome in which the affected newborns are significantly larger than normal at birth (macrosomia) and continue to develop and acquire weight at an exceptional rate. People with SGBS have characteristic facial traits such as a significant distance between the eyes (hypertelorism), an exceptionally wide mouth (macrostomia) with macroglossia (a huge tongue), and abnormalities of the palate.
Other symptoms include extra nipples, birth malformations such as an umbilical hernia (protrusion of the lining of the abdomen), and skeletal anomalies. SGBS is classified into two clinical subgroups. The typical form (SGBS or SGBS type I) is linked to GPC3 (glypican 3) mutations, while the deadly variant (SGBS type II) is linked to a different area of chromosome X (Xp22.2). The infantile fatal version of SGBS is commonly linked with hydrops fetalis.
What Are the Causes of Simpson-Golabi-Behmel Syndrome?
Simpson-Golabi-Behmel syndrome is most commonly caused by mutations in the GPC3 gene. This gene codes for a protein called glypican 3, which inhibits the developmental pathway known as the hedgehog signaling pathway. During embryonic development, this route is crucial for cell growth and division, cell specialization, and the normal shaping of many regions of the body. Glypican 3 is thought to help shape the body by inducing specific cells to self-destruct when they are no longer needed. Mutations in the GPC3 gene prevent glypican 3 from blocking the hedgehog signaling pathway. This pathway's overactivity causes an increase in cell growth and division beginning before birth. It has been reported that SGBS type II is caused by GPC4 gene duplication, which regulates cell division and proliferation.
How Is Simpson-Golabi-Behmel Syndrome Inherited?
Simpson-Golabi-Behmel syndrome disorder is inherited in an X-linked manner. An illness is called X-linked if the defective gene that causes the disorder is situated on the X chromosome. In males, one mutated copy of the gene in each cell is enough to trigger the disease as they have only one X chromosome. Females have two copies of the X chromosome, and one mutated copy of the gene in each cell usually causes less severe health problems than males or may generate no signs or symptoms.
What Are the Symptoms of Simpson-Golabi-Behmel Syndrome?
The symptoms associated with Simpson-Golabi-Behmel syndrome are the following.
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Macroglossia.
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Organomegaly.
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Macrosomia.
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Neoplasms.
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Brain malformations.
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Hypotonia.
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Intellectual disability.
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Supernumerary fingers or toes.
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Neonatal hypoglycemia.
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Advanced bone age.
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Cardiac defects.
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Supernumerary nipples.
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Vertebral defects.
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Kidney diseases.
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Developmental defects.
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Broad foot.
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Atrial septal defects.
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Short neck.
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Congenital hip dislocation.
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Neuroblastoma.
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Hoarse voice.
What Are the Diagnostic Tests Used for Simpson-Golabi-Behmel Syndrome?
Simpson-Golabi-Behmel syndrome detection occurs with a routine doctor appointment during which the fundal height is assessed or during an ultrasound examination. Maternal hyperglycemia or wrong dates are the most common causes of large gestational age fetuses (LGA). If these two possibilities are ruled out, an ultrasound is conducted to look for abnormalities. A clinical geneticist is required to assist in selecting testing and possible diagnosis. Clinical findings, pedigree analysis, and medical problems of patients are used to make a diagnosis. A karyotype concentrating on the X chromosome, array CGH (comparative genomic hybridization) or MLPA (multiplex ligation-dependent probe amplification) analysis, and mutation analysis of the GPC3 or GPC4 are used in the genetic approach. Next-generation sequencing technologies have enabled the simultaneous assessment of several genes implicated in overgrowth.
In patients with SGBS, no biochemical or endocrinological markers have been identified. CT (computerized tomography) scan or brain MRI (magnetic resonance imaging) abnormalities of the central nervous system are common; midline defects such as aberrant corpus callosum, hydrocephalus, and central lipomata may be observed. A characteristic sign of congenital anomaly of the proximal phalanx and index finger hypoplasia fingernail are seen on X-rays. The majority of patients with Simpson-Golabi-Behmel syndrome have rib abnormalities. Prenatal testing is available if a known mutation exists in the family. Prenatal testing is also possible if the mother has the moderate SGBS phenotype and male family members have the positive SGBS phenotype.
What Are the Treatment Options for Simpson-Golabi-Behmel Syndrome?
Treatment for SGBS comprises newborn hypoglycemia treatment and multidisciplinary support from specialists. Depending on the clinical symptoms associated with Simpson-Golabi-Behmel syndrome, the treatment is planned. Surgery, higher glucose intake, special education, occupational therapy, physical therapy, and speech therapy are some common methods. Other treatment options include the following.
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Monitoring for hypoglycemia throughout the neonatal period.
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Physical examination to monitor for scoliosis during periods of rapid growth; radiographs as needed.
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If the initial assessment indicates that development is normal, social and intellectual development should be monitored regularly.
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If renal abnormalities are evident, renal function should be monitored.
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Physical exams to assess tumor risk; every three months till the age of four, every four months from the age of four to the age of seven, and biannually after the age of seven.
Conclusion
The Simpson-Golabi-Behmel syndrome (SGBS) is a rare condition of overgrowth and various congenital abnormalities caused by mutations in a semi-dominant X-linked gene encoding Glypican 3 (GPC3). It has a wide clinical range from extremely mild forms in carrier females to deadly variants with failure to thrive in males. In early childhood, about ten percent of patients with Simpson-Golabi-Behmel syndrome develop malignant or noncancerous tumors. This condition can be diagnosed based on specific symptoms and genetic tests. Treatment for SGBS includes management of clinical symptoms and regular monitoring of complications.
