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GeneReviews provides information about selected national organizations and resources for the benefit of the reader. GeneReviews is not responsible for information provided by other organizations. Information that appears in the Resources section of a GeneReview is current as of initial posting or most recent update of the GeneReview. Search GeneTests for this disorder and select
for the most up-to-date Resources information.—ED.
GeneReviews designates a molecular genetic test as clinically available only if the test is listed in the GeneTests Laboratory Directory by either a US CLIA-licensed laboratory or a non-US clinical laboratory. GeneTests does not verify laboratory-submitted information or warrant any aspect of a laboratory's licensure or performance. Clinicians must communicate directly with the laboratories to verify information.—ED.
Information in the Molecular Genetics tables is current as of initial posting or most recent update. —ED.
Genetics clinics are a source of information for individuals and families regarding the natural history, treatment, mode of inheritance, and genetic risks to other family members as well as information about available consumer-oriented resources. See the GeneTests Clinic Directory.
Support groups have been established for individuals and families to provide information, support, and contact with other affected individuals. The Resources section may include disease-specific and/or umbrella support organizations.
For current information on availability of genetic testing for disorders included in this section, see GeneTests Laboratory Directory. —ED.
Genetic counseling is the process of providing individuals and families with information on the nature, inheritance, and implications of genetic disorders to help them make informed medical and personal decisions. The following section deals with genetic risk assessment and the use of family history and genetic testing to clarify genetic status for family members. This section is not meant to address all personal, cultural, or ethical issues that individuals may face or to substitute for consultation with a genetics professional. To find a genetics or prenatal diagnosis clinic, see the GeneTests Clinic Directory.
Disease characteristics. Simpson-Golabi-Behmel syndrome (SGBS) is characterized by pre- and postnatal macrosomia, distinctive craniofacies (macrocephaly, ocular hypertelorism, macrostomia, macroglossia, palatal abnormalities), and commonly, mild to severe mental retardation with or without structural brain anomalies. Other, variable findings include supernumerary nipples, diastasis recti/umbilical hernia, congenital heart defects, renal defects (nephromegaly, multicystic kidneys, hydronephrosis, hydroureter, duplicated ureters), and GI anomalies (pyloric ring, Meckel's diverticulum, intestinal malrotation, hepatosplenomegaly, hyperplasia of islets of Langerhans, choledochal cysts, polysplenia). Skeletal anomalies can include vertebral fusion, scoliosis, pectus excavatum, rib anomalies, winged scapula, and congenital hip dislocation. Hand anomalies can include large hands, broad thumbs, brachydactyly, syndactyly, clinodactyly, and postaxial polydactyly. Tumor frequency is about 10%; reported tumors include Wilms tumor, hepatoblastoma, adrenal neuroblastoma, gonadoblastoma, and hepatocellular carcinoma.
Diagnosis/testing. The diagnosis of SGBS is based on clinical findings, family history consistent with X-linked inheritance, and molecular genetic testing of GPC3, the only gene currently known to be associated with SGBS. Mutation detection rate using sequence analysis and deletion analysis is 37%-70%. Testing is clinically available.
Management. Treatment of manifestations: prompt treatment of neonatal hypoglycemia; management of cleft lip and/or palate or macroglossia and related feeding difficulties by a craniofacial team; speech therapy as needed; referral to a pediatric orthopedist, cardiologist, and urologist as needed; neurodevelopmental assessment to determine need for special education, occupational therapy, and/or physical therapy. Prevention of secondary complications: for those with congenital heart disease, anticoagulation and antibiotic prophylaxis as needed. Surveillance: monitoring for hypoglycemia in the first few days of life, scoliosis by physical examination, social and intellectual development on a routine basis for those whose development appears normal on initial assessment, renal function if renal anomalies are present; routine surveillance for Wilms tumor, gonadoblastoma, hepatocellular carcinoma, neuroblastoma; annual lifelong chest radiographs.
Genetic counseling. Simpson-Golabi-Behmel syndrome is inherited in an X-linked manner. If the mother of the proband has a disease-causing mutation, the chance of transmitting it in each pregnancy is 50%. Males who inherit the mutation will be affected; females who inherit the mutation will be carriers and will usually not be affected. Males with SGBS will pass the disease-causing mutation to all of their daughters and none of their sons. If the GPC3 mutation has been identified in a family member, both carrier testing for at-risk relatives and prenatal testing for at-risk pregnancies are possible.
The diagnosis of Simpson-Golabi-Behmel syndrome (SGBS) is based on clinical findings, family history consistent with X-linked inheritance, and the results of molecular genetic testing of GPC3.
No clinical diagnostic criteria have been established. The diagnosis is suspected in males with the following:
Macrosomia (weight or length ≥95th percentile when adjusted for sex and age).
Characteristic facial features
Macrocephaly [occipitofrontal circumference (OFC) ≥95th percentile when adjusted for sex and age]
Ocular hypertelorism, epicanthal folds, and downslanting palpebral fissures
Redundant, furrowed skin over the glabella
Wide nasal bridge and anteverted nares in infants; broad nose and "coarse" facial appearance in older individuals
Macrostomia (abnormally large mouth)
Macroglossia (abnormally large tongue)
Midline groove in the lower lip and/or deep furrow in the middle of the tongue
Cleft lip and/or submucous cleft palate (with a bifid uvula); high and narrow palate [Hughes-Benzie et al 1996]
Small mandible (micrognathia) in neonates; macrognathia in older individuals
Multiple congenital anomalies (see Natural History)
Congenital heart disease (structural and conduction defects)
Supernumerary nipples
Diastasis recti/umbilical hernia
Diaphragmatic hernia
Renal dysplasia/nephromegaly
Cryptorchidism/hypospadias
Hand anomalies (brachydactyly, cutaneous syndactyly, polydactyly)
GeneReviews designates a molecular genetic test as clinically available only if the test is listed in the GeneTests Laboratory Directory by either a US CLIA-licensed laboratory or a non-US clinical laboratory. GeneTests does not verify laboratory-submitted information or warrant any aspect of a laboratory's licensure or performance. Clinicians must communicate directly with the laboratories to verify information.—ED.
Gene. GPC3 is the only gene known to be associated with Simpson-Golabi-Behmel syndrome (SGBS).
Other loci. A multiple congenital anomaly syndrome postulated to be a severe form of SGBS, or so-called infantile lethal variant, maps to Xp22. It is considered in this review to be a distinct disorder with overlapping phenotypic features [Terepolsky et al 1995]. (see Differential Diagnosis).
Clinical uses
Confirmatory diagnostic testing
Carrier testing
Prenatal diagnosis
Clinical testing
Sequence analysis/ mutation scanning and deletion/duplication analysis. The detection rate for GPC3 mutations and deletions in individuals with SGBS ranges widely from 37% (7/19) [Li et al 2001] to 70%; 7/10 in the study of Veugelers et al (2000) and 26/37 in the study of Lin et al (1999). Lin et al (1999) hypothesized that the high detection rate of 70% may reflect a sampling bias in their study.
Note: In the study by Li et al (2001), two individuals who prior to molecular genetic testing had been diagnosed with other overgrowth syndromes (Perlman syndrome and Sotos syndrome) were subsequently found to have a GPC3 mutation, thus establishing the diagnosis of SGBS.
Table 1 summarizes molecular genetic testing for this disorder.
| Test Method | Mutations Detected | Mutation Detection Rate | Test Availability |
|---|---|---|---|
| Sequence analysis | GPC3 sequence variants | 37%-70% 1 | Clinical
 |
| Duplication/deletion testing | GPC3 deletions |
Interpretation of test results. For issues to consider in interpretation of sequence analysis results, click here.
No other phenotypes are known to be associated with mutations in GPC3.
Simpson-Golabi-Behmel syndrome (SGBS) is characterized by pre- and postnatal macrosomia, distinctive facies, and variable visceral, skeletal, and neurodevelopmental abnormalities.
Macrosomia. Virtually all persons with SGBS have pre- and postnatal overgrowth. As with other macrosomic syndromes, hypoglycemia may be present in the neonatal period.
Macrocephaly. See Clinical Diagnosis.
Characteristic facies. See Clinical Diagnosis.
Eyes. Esotropia, cataracts, and coloboma of the optic disc [Golabi & Rosen 1984] have been noted. Ocular nerve palsies and strabismus can occur.
Ears. Minor ear abnormalities are frequent, most often preauricular tags, fistulas, ear lobule creases, and helical dimples. Conductive hearing loss has been described [Golabi & Rosen 1984].
Neck. Cystic hygroma has been described [Chen et al 1993].
Thoracoabdominal wall. Supernumerary nipples are common, either one or multiple, unilateral or bilateral. Diastasis recti and umbilical hernias are observed frequently; however, true omphalocele is rare.
Cardiothoracic. Congenital heart defects are variable; septal defects are common. Pulmonic stenosis, aortic coarctation, transposition of the great vessels, and patent ductus arteriosus or patent foramen ovale have been reported. Conduction defects and arrhythmias have frequently been described [Lin et al 1999].
Genitourinary. Nephromegaly, multicystic kidneys, hydronephrosis, hydroureter, and duplicated ureters are described. Other genitourinary anomalies include hypospadias, bifid scrotum, cryptorchidism, hydrocele, and inguinal hernia [Hughes-Benzie et al 1996].
Gastrointestinal. GI anomalies include pyloric ring, Meckel's diverticulum, intestinal malrotation [Golabi & Rosen 1984], hepatosplenomegaly, pancreatic hyperplasia of islets of Langerhans, choledochal cysts [Kim et al 1999], duplication of the pancreatic duct, and polysplenia.
Skeletal. Skeletal anomalies can include vertebral fusion, scoliosis, pectus excavatum, rib anomalies (including cervical ribs), winged scapula, congenital hip dislocation [Terepolsky et al 1995], small sciatic notches, and flared iliac wings [Chen et al 1993]. Extra lumbar vertebrae, spina bifida occulta, coccygeal skin tag, and bony appendage have also been documented [Golabi & Rosen 1984].
Hand anomalies, including large hands, broad thumbs, and brachydactyly, are common. Other findings include syndactyly, clinodactyly, and postaxial polydactyly. Striking index finger hypoplasia with congenital abnormalities of the proximal phalanx has been reported [Day & Fryer 2005]. Nail dysplasia, hypoplasia (particularly of the index finger), and hypoconvexity are common.
Advanced bone age, including presence of ossified carpal bones in a newborn, has been described [Chen et al 1993].
Central nervous system (CNS). Normal intelligence has been described, but mild to severe mental retardation is common, with language delay being the most characteristic description.
Neurologic manifestations are perhaps the most varied findings. Hypotonia and absent primitive reflexes, a high-pitched cry in neonates, seizures, and abnormal EEG have all been described.
CNS malformations include agenesis of the corpus callosum, Chiari malformation and hydrocephalus [Young et al 2006], and aplasia of the cerebellar vermis.
Neoplasia. An absolute incidence and relative risk for tumors has not been established; however, in a review of more than 100 persons with SGBS, Li et al (2001) found a tumor frequency of about 10%. At least five tumor types have been described: Wilms tumor (4 cases), hepatoblastoma (2), adrenal neuroblastoma (1), gonadoblastoma (1) and hepatocellular carcinoma (1) [Lapunzina et al 1998, Li et al 2001, Lapunzina 2005]. (See Wilms Tumor Overview.)
Other
Diaphragmatic hernia and associated lung hypoplasia [Chen et al 1993] (See Congenital Diaphragmatic Hernia Overview.)
Thymic hypoplasia and generalized lymphoid atrophy [Chen et al 1993]
Carrier females can have manifestations of SBGS including short narrow palpebral fissures, upturned nasal tip with prominent columella, macrostomia, prominent chin, hypoplastic fingernails, coccygeal skin tag and bony appendage, extra lumbar and thoracic vertebrae, and accessory nipples [Golabi & Rosen 1984].
In a study of genotype-phenotype correlations, Mariani et al (2003) determined that all deletions and point mutations occurring in the eight GPC3 exons result in loss of function with no phenotypic distinctions based on size or position of a deletion or point mutation.
Concurrent gene deletions of GPC3 and the related GPC4 gene, which flanks the centromeric end of GPC3 on Xq26, have been described [Veugelers et al 1998]. However, isolated GPC4 mutations have not been identified in SGBS. No evidence suggests that the phenotype in individuals with mutations involving both GPC3 and GPC4 varies from the phenotype resulting from mutations of GPC3 alone.
To date, all males with a GPC3 mutation have had clinical findings of SGBS [authors, personal observation].
Penetrance in heterozygous females is unknown.
SGBS was initially described by Simpson et al (1975), with later accounts by Golabi & Rosen (1984) and Behmel et al (1984).
Terms no longer in use for SGBS:
Gigantism-dysplasia syndrome
Encephalo-tropho-schisis syndrome
Golabi-Rosen syndrome
Simpson dysmorphia syndrome
The prevalence of SGBS is unknown.
For current information on availability of genetic testing for disorders included in this section, see GeneTests Laboratory Directory. —ED.
A severe form of Simpson-Golabi-Behmel syndrome (SGBS), or so-called infantile lethal variant, maps to Xp22 and is postulated to be a distinct disorder with overlapping phenotypic features. Clinical features described in four individuals include hydrops fetalis, jaundice, brisk deep tendon reflexes, seizures, and trilobate left lung [Terepolsky et al 1995, Brzustowicz et al 1999].
Beckwith-Wiedemann syndrome (BWS) is characterized by macrosomia, macroglossia, visceromegaly, embryonal tumors (e.g., Wilms tumor, hepatoblastoma, neuroblastoma, rhabdomyosarcoma), omphalocele, neonatal hypoglycemia, ear creases/pits, adrenocortical cytomegaly, and renal abnormalities (e.g., medullary dysplasia, nephrocalcinosis, medullary sponge kidney, and nephromegaly). BWS is caused by a range of abnormalities of chromosome 11p15. BWS demonstrates the most clinical similarities with SGBS including macrosomia, macroglossia, ear anomalies, genitourinary malformations, and an increased incidence of tumors. However, the facies in these two syndromes are appreciably different, the skeletal abnormalities seen in SGBS are not present in BWS, and omphalocele seen in BWS is rare in SGBS. Additionally, the X-linked inheritance of SGBS may help to differentiate these two overgrowth syndromes [Pilia et al 1996].
Sotos syndrome is characterized by a typical facial appearance, intellectual impairment, and overgrowth involving both height and head circumference. It is associated with neonatal jaundice, scoliosis, seizures, strabismus, conductive hearing loss, congenital cardiac anomalies, renal anomalies, and behavioral problems. The risk of sacrococcygeal teratoma and neuroblastoma is slightly increased. About 80%-90% of individuals with Sotos syndrome have a demonstrable mutation or deletion of NSD1. Inheritance is autosomal dominant.
Weaver syndrome shares clinical features of overgrowth, umbilical hernia, ear anomalies, hypotonia, advanced bone age, vertebral defects, and hypertelorism, but has different facies and more prominent psychomotor delay. No molecular testing is currently available; thus, the diagnosis is made on clinical grounds.
Nevoid basal cell carcinoma syndrome (NBCCS) (also known as Gorlin syndrome) is characterized by multiple jaw keratocysts frequently beginning in the second decade of life and/or basal cell carcinomas usually from the third decade onwards. About 60% of individuals have a recognizable appearance with macrocephaly, bossing of the forehead, coarse facial features, and facial milia. Most individuals with NBCCS have skeletal anomalies such as bifid ribs or wedge-shaped vertebrae. Other less common findings include ectopic calcification, particularly in the falx; cardiac and ovarian fibromas; and medulloblastoma [primitive neuroectodermal tumor (PNET)] in early childhood. In about 60%-85% of individuals fulfilling diagnostic criteria, it is possible to identify a germline mutation of the PTCH gene. Inheritance is autosomal dominant.
Fryns syndrome, an autosomal recessive multiple congenital anomaly syndrome, is characterized by coarse facies, diaphragmatic hernia with lung hypoplasia, distal limb hypoplasia and malformations of the cardiovascular system, gastrointestinal system, genitourinary system (renal cystic dysplasia), and central nervous system (arrhinencephaly, Dandy-Walker anomaly, agenesis of the corpus callosum).
Other syndromes that may share overlapping features:
Perlman syndrome, a rare autosomal recessive condition, with macrosomia and a high incidence of Wilms tumor; facial features are distinctive and neonatal mortality is high.
Nevo syndrome, which shares vertebral anomalies, ear malformations, cryptorchidism, overgrowth, and mental retardation with SGBS
Marshall-Smith syndrome, which shares advanced bone age and mental retardation with SGBS; differences include facial features and predisposition to fractures.
Elejalde syndrome, or acrocephalopolydactylous dysplasia. Infrequently described, Elejalde syndrome includes findings of macrosomia, abnormal facies, craniosynostosis with acrocepaly, omphalocele, organomegaly, cystic renal dysplasia, and polydactyly.
Infant of a diabetic mother syndrome. Infants born to diabetic mothers (IDM) have a higher rate of congenital malformations. Sacral agenesis or hypogenesis and/or caudal dysgenesis are classic findings [Williamson 1970], but other frequently observed anomalies include congenital heart defects, renal anomalies, vertebral anomalies, limb defects, and structural brain abnormalities.
Mosaic trisomy 8. Phenotype is variable, with characteristic findings of advanced growth, long slender trunk with multiple skeletal abnormalities (spinal deformities, contractures of fingers and toes), absence of the corpus callosum, and moderate mental retardation. Typical facial features include high, prominent forehead, hypertelorism, full lips, and micrognathia.
Mosaic tetrasomy 12p (or Pallister-Killian syndrome), characterized by variegated skin pigmentation, facial anomalies including prominent forehead with sparse anterior scalp hair, ocular hypertelorism, short nose with anteverted nares, flat nasal bridge, as well as developmental delay
Assessment of upper airway sufficiency if macroglossia is present
Evaluation by a feeding specialist if clefting causes significant feeding difficulties
Assessment of neonates for hypoglycemia
Cardiac evaluation including chest radiograph, electrocardiogram, and echocardiogram
Renal ultrasound examination to evaluate for genitourinary malformations
Abdominal ultrasound examination to evaluate for intra-abdominal tumors
Abdominal CT if ultrasound examination appears to be normal but visceral anomalies are suspected
Prompt treatment of hypoglycemia if present
Referral to a craniofacial team for management of cleft lip and/or palate, or macroglossia and related feeding difficulties
Speech therapy as needed
Referral to a pediatric orthopedist for the treatment of vertebral malformations if present
Referral to a pediatric cardiologist for management of congenital heart defects and/or cardiac conduction defects
Referral to a pediatric urologist for surgical correction of genitourinary anomalies such as hypospadias and cryptorchidism
Neurodevelopmental assessment to develop an individual treatment plan that may include special education, occupational therapy, and physical therapy
Antiepileptic drugs (AEDs) if seizures are present
For individuals with congenital heart disease, either corrected or uncorrected:
Anticoagulation to prevent thromboembolic events
Antibiotic prophylaxis to prevent bacterial endocarditis
Monitoring for hypoglycemia in the first few days of life
Physical examination to monitor for scoliosis; radiographs as needed
If development appears to be normal on initial assessment, routine monitoring of social and intellectual development
Monitoring of renal function if renal anomalies are present
Cancer surveillance. Physical examinations to monitor for tumor risk [Lapunzina 2005]:
Every three months until age four years
Every four months from age four to seven years
Biannually after age seven years
The following screening recommendations require further study to determine benefit. The clinician and family should discuss the methods to be used:
Wilms tumor. Abdominal ultrasound examination every three or four months from birth until at least age seven or eight years, and yearly thereafter [Choyke et al 1999, Lapunzina 2005]. Abdominal ultrasound examination should assess for both Wilms tumor and hepatic tumors.
Note: When associated with an overgrowth syndrome, the risk of Wilms tumor decreases after age eight years [Beckwith 1998].
Gonadoblastoma or hepatocellular carcinoma. Serial measurement of serum alpha fetoprotein and beta human chorionic gonadotropin concentrations with the following suggested frequency [Lapunzina 2005]:
Every four months until age four years
Every six months between ages four and seven years
Annually after age seven years
Neuroblastoma. Measurements of urinary catecholamine metabolites including vanillylmandelic acid and homovanillic acid as well as urinary free fractionated catecholamines with the following suggested frequency [Lapunzina 2005]:
Every four months until age four years
Every six months between ages four and seven years
Annually after age seven years
Annual lifelong chest radiograms have also been suggested [Lapunzina 2005].
Search ClinicalTrials.gov for access to information on clinical studies for a wide range of diseases and conditions.
Genetic counseling is the process of providing individuals and families with information on the nature, inheritance, and implications of genetic disorders to help them make informed medical and personal decisions. The following section deals with genetic risk assessment and the use of family history and genetic testing to clarify genetic status for family members. This section is not meant to address all personal, cultural, or ethical issues that individuals may face or to substitute for consultation with a genetics professional. To find a genetics or prenatal diagnosis clinic, see the GeneTests Clinic Directory.
Simpson-Golabi-Behmel syndrome (SGBS) is inherited in an X-linked manner.
Parents of a proband
The father of an affected male will not have the disease nor will he be a carrier of the mutation.
In a family with more than one affected individual, the mother of an affected male is an obligate carrier.
If pedigree analysis reveals that the proband is the only affected family member, the mother may be a carrier or the affected male may have a de novo gene mutation, in which case the mother is not a carrier. The frequency of de novo mutations is not known.
Because some female carriers have physical findings of SGBS, physical examination of the proband's mother for features of SGBS is helpful.
If a woman has more than one affected son and the disease-causing mutation cannot be detected in her leukocyte DNA, she has germline mosaicism.
When an affected male represents a simplex case (i.e., the only affected individual in the family), several possibilities regarding his mother's carrier status need to be considered:
He has a de novo disease-causing mutation in the GPC3 gene and his mother is not a carrier.
His mother has a de novo disease-causing mutation in the GPC3 gene, either a) as a "germline mutation" (i.e., present at the time of her conception and therefore in every cell of her body); or b) as "germline mosaicism" (i.e., present in some of her germ cells only).
His mother has a disease-causing mutation that she inherited from a maternal female ancestor.
Sibs of a proband
The risk to sibs depends upon the carrier status of the mother.
If the mother of the proband has a disease-causing mutation, the chance of transmitting the disease-causing mutation in each pregnancy is 50%. Male sibs who inherit the mutation will be affected; female sibs who inherit the mutation will be carriers and will usually not be affected.
Germline mosaicism has been demonstrated. Thus, even if the disease-causing mutation present in the proband has not been identified in the mother's DNA, sibs of the proband are still at increased risk of inheriting the disease-causing mutation.
Offspring of a proband. Males with SGBS will pass the disease-causing mutation to all of their daughters and none of their sons. Thus, female offspring of the proband will be carriers, while male offspring of the proband will not be affected.
Other family members of a proband. The proband's maternal aunts may be at risk of being carriers and the aunt's offspring, depending upon their gender, may be at risk of being carriers or of being affected.
Carrier testing of at-risk female relatives is available on a clinical basis if the mutation has been identified in an affected family member.
Family planning. The optimal time for determination of genetic risk, clarification of carrier status, and discussion of the availability of prenatal testing is before pregnancy.
DNA banking. DNA banking is the storage of DNA (typically extracted from white blood cells) for possible future use. Because it is likely that testing methodology and our understanding of genes, mutations, and diseases will improve in the future, consideration should be given to banking DNA of affected individuals. DNA banking is particularly relevant in situations in which the sensitivity of currently available testing is less than 100%. See DNA Banking for a list of laboratories offering this service.
If the GPC3 mutation has been identified in a family member, prenatal testing is possible for pregnancies at risk. The usual procedure is to determine fetal sex by analysis of fetal cells obtained by chorionic villus sampling (CVS) at about ten to 12 weeks' gestation or by amniocentesis usually performed at about 15-18 weeks' gestation. If the karyotype is 46,XY, DNA from fetal cells can be analyzed for the known disease-causing mutation.
Note: Gestational age is expressed as menstrual weeks calculated either from the first day of the last normal menstrual period or by ultrasound measurements.
Preimplantation genetic diagnosis (PGD) may be available for families in which the disease-causing mutation has been identified in an affected family member. For laboratories offering PGD, see
.
Information in the Molecular Genetics tables is current as of initial posting or most recent update. —ED.
| Gene Symbol | Chromosomal Locus | Protein Name |
|---|---|---|
| GPC3 | Xq26 | Glypican-3 |
Data are compiled from the following standard references: Gene symbol from HUGO; chromosomal locus, locus name, critical region, complementation group from OMIM; protein name from Swiss-Prot.
| Gene Symbol | Entrez Gene | HGMD |
|---|---|---|
| GPC3 | 2719 (MIM No. 300037) | GPC3 |
For a description of the genomic databases listed, click here.
Normal allelic variants: GPC3 includes eight exons that span more than 500 kb.
Pathologic allelic variants: All eight exons have been found to harbor either deletions or point mutations that lead to the Simpson-Golabi-Behmel syndrome (SGBS) phenotype.
Approximately 50% of GPC3 gene deletions involve exon 8 [Veugelers et al 2000]. Point mutations include splice site, frameshift, missense, and nonsense mutations [Veugelers et al 2000]. Point mutations have been described in all exons. As expected, most point mutations occur in exon 3, the largest exon.
Normal gene product: Glypican-3 is a glycosylphosphatidylinositol-linked cell surface heparan sulfate proteoglycan [Pilia et al 1996]. Heparan sulfate proteoglycans bind and regulate the activities of a variety of extracellular ligands essential to cellular functions. Glypicans have a role in cell growth and cell division.
Abnormal gene product: The mechanism by which a loss-of-function GPC3 mutation leads to the SGBS phenotype is unknown.
GeneReviews provides information about selected national organizations and resources for the benefit of the reader. GeneReviews is not responsible for information provided by other organizations. Information that appears in the Resources section of a GeneReview is current as of initial posting or most recent update of the GeneReview. Search GeneTests for this disorder and select
for the most up-to-date Resources information.—ED.
Overgrowth Syndrome Registry
Overgrowth Syndrome Registry
Medical Genetic Searches: A specialized PubMed search designed for clinicians that is located on the PubMed Clinical Queries page.
No specific guidelines regarding genetic testing for this disorder have been developed.
Aaron James is in his third year in the School of Medicine at UCSF.
Kathy Culver is a board-certified genetic counselor.
Mahin Golabi, MD, MPH, is board certified in Medical Genetics and Pediatrics, and former clinical professor in Clinical Genetics at University of California, San Francisco.
19 December 2006 (me) Review posted to live Web site
6 July 2006 (kc) Original submission
