A female sibling of the patient, who presented with a cleft palate and hepatoblastoma, carries the same chromosomal rearrangement and a paradoxical pattern of X-chromosome inactivation. [nature.com]

We also present a discussion of the implications of X-linked recessive disease identification in female patients. Case Presentation A 20-month-old female with developmental delay presented with a palpable abdominal mass. [sciencerepository.org]

Very few cases of female presentations of Simpson-Golabi-Behmelsyndrome have been described. [scholarlycommons.hcahealthcare.com]

These findings highlight the importance of family history, autopsy and molecular analysis in prenatal cases presenting with non isolated congenital diagphragmatic hernia on fetal ultrasound. [ashg.org]

Involvement of central nervous system presents with variable degrees of intellectual disability, motor delay and speech delay. [orpha.net]

• Splenomegaly

  And/Or Closure Of The Ventricular Septal Defect Neck Short And Broad Neck Muscles Hypotonia Nervous System Central Nervous System Abnormalities And Seizures Gastrointestinal System Hepatomegaly Malformations And Enlarged Pancreas Hematopoietic System Splenomegaly [neo-genetics.com]

  […] megalocephaly / megacephaly - Macroglossia / tongue protrusion / proeminent / hypertrophic - Macrostomia / big mouth - Multicystic kidney / renal dysplasia - Postaxial polydactyly (hand) - Prognathism / prognathia - Short foot / brachydactyly of toes - Splenomegaly [csbg.cnb.csic.es]

  […] macrocephaly with coarse face, macroglossia, hypertelorism, dental malocclusion, palatal abnormalities), supernumerary nipples, congenital heart defects and arrhythmias, vertebral segmental defects, abdominal visceromegaly (renal dysplasia/nephromegaly, splenomegaly [orpha.net]

  […] birth (congenital diaphragmatic hernia) occurs rarely Extra nipples (supernumerary nipples) in half of people Kidney abnormalities in 33% of people Large kidney (nephromegaly) in half of people Large liver (hepatomegaly) in half of people Large spleen (splenomegaly [rarediseases.org]

• Disability

  X-Linked Intellectual Disability panels are available for 30, 60, and 90 genes. How to Order [egl-eurofins.com]

  GPC3 Deletion and Duplication Analysis GPC3 Whole Gene Sequencing Overgrowth and Intellectual Disability Deletion and Duplication Panel Overgrowth and Intellectual Disability NGS Panel Search Tests Search this site Search for Browse All Tests Tests by [ddccliniclab.org]

  759.89 Birt-Hogg-Dube syndrome 759.89 Brachman-de Lange syndrome (Amsterdam dwarf, intellectual disabilities, and brachycephaly) 759.89 Brachymorphism and ectopia lentis 759.89 Bruck-de Lange disease or syndrome (Amsterdam dwarf, intellectual disabilities [icd9data.com]

  […] encephalopathy with severe muscular hypotonia, dysmorphism, multiple congenital anomalies, and early death ("MCAHS2"), (ii) neurodegenerative encephalopathy with systemic iron overload (ferro-cerebro-cutaneous syndrome, "FCCS"), and (iii) intellectual disability [zora.uzh.ch]

• Coarse Facial Features

  The main features pointing towards the diagnosis were macrosomia, coarse facial features and macroglossia with a midline groove in the tongue. Proband B developed a Wilms tumour. He was found to have a novel mutation causing a premature stop codon. [samj.org.za]

  facial features, widely spaced eyes, a short nose with anteverted nares, gingival overgrowth, a wide mouth, short limbs with short distal phalanges, and a small penis. [zora.uzh.ch]

  Simpson-Golabi-Behmel syndrome (SGBS) is an X-linked disorder that typically displays prenatal and postnatal overgrowth, coarse facial features, and congenital anomalies, with severe, sometimes fatal consequences in affected males, and limited effects [taylorfrancis.com]

• Weight Gain

  […] fluids in different fetal parts (hydrops fetalis) The symptoms of Simpson-Golabi-Behmel Syndrome may include a distinctive facial appearance (such as widely-spaced eyes, a wide and upturend nose, abnormally large mouth), an abnormal rate of growth and weight [dovemed.com]

  For abnormally short stature (with or without poor weight gain), many publications aimed at guiding practitioners are available to assist in a rapid diagnosis [e.g., Bithoney et al. (12), Rose et al. (13), and Jaffe (14)]. [frontiersin.org]

• Abdominal Pain

  Clinical presentations of MIS-C include fever, abdominal pain, vomiting, diarrhea, skin rash, mucocutaneous lesions, hypotension and cardiovascular and neurologic compromise205,206. [nature.com]

• Hepatomegaly

  These features included macrocephaly, macroglossia, post axial polydactyl of the left hand, bilateral low insertion of the thumb, multiple accessory nipples, hepatomegaly, and congenital heart. [ajol.info]

  Valve Leaflets Into The Septal Defects Resulting In Aortic Regurgitation And/Or Closure Of The Ventricular Septal Defect Neck Short And Broad Neck Muscles Hypotonia Nervous System Central Nervous System Abnormalities And Seizures Gastrointestinal System Hepatomegaly [neo-genetics.com]

  […] coarse face, macroglossia, hypertelorism, dental malocclusion, palatal abnormalities), supernumerary nipples, congenital heart defects and arrhythmias, vertebral segmental defects, abdominal visceromegaly (renal dysplasia/nephromegaly, spleenomegaly and hepatomegaly [orpha.net]

  […] abnormal sacrum, absent nails/claws, cleft palate most often associated with a cleft of the lower lip, coarse facial features, macroglossia, coloboma, congenital heart defects (ventricular septal defect, atrial septal defect), diaphragmatic hernia, hepatomegaly [accessanesthesiology.mhmedical.com]

• Hepatosplenomegaly

  Simpson-Golabi-Behmel syndrome is characterized by: polyhydramnios neonatal recurrent hypoglycemia 6 facial deformities, including cleft lip and palate 9, macrostomia, macroglossia and dental malocclusion 12 hepatosplenomegaly multicystic dysplasia of [radiopaedia.org]

  Other features include stocky constitution, supernumerary nipples, rib abnormalities, pectus excavatum, bundle-branch or AV-block, hepatosplenomegaly, umbilical or inguinal hernia, cryptorchidism, nail dysplasia, abnormal dermatoglyphics, and sometimes [whonamedit.com]

  Supernumerary nipples, rib abnormalities, pectus excavatum, hepatosplenomegaly, umbilical or inguinal hernia, and cryptorchidism may be present. Cardiac abnormalities are frequent, occurring in about one third of the cases. [react-community.org]

  Other clinical findings may include heart defects, malformed or abnormally large kidneys, an enlarged liver and spleen (hepatosplenomegaly), skeletal abnormalities, and gastrointestinal or genitourinary malformations. [invitae.com]

  Simpson-Golabi-Behmel syndrome can also cause heart defects, malformed or abnormally large kidneys, an enlarged liver and spleen (hepatosplenomegaly), and skeletal abnormalities. [ghr.nlm.nih.gov]

• Macrostomia

  Figure 1: The patient exhibited macrocephaly, macrostomia, and coarse facial features. [journals.lww.com]

  The infantile lethal form of SGBS is sometimes known as SGBS type 2. [1] [2] People with SGBS typically have distinctive facial features, including a large distance between the eyes ( hypertelorism ), an unusually wide mouth ( macrostomia ) with a large [rarediseases.info.nih.gov]

  midline groove in tongue, vertebral anomalies, intestinal malrotation pCME2(Belgium) / / Prematurely born (37 weeks –birth weight and length at P97), postnatal overgrowth, omphalocoele, hypogonadism, macrostomia, broad great toes, overlapping second [doi.org]

  Simpson Golabi Behmel Syndrome (SGBS) is an X-linked overgrowth syndrome with coarse craniofacial features that include hypertelorism, epicanthal folds, macrostomia, macroglossia, and antiverted nares. [oxfordmedicine.com]

  Simpson-Golabi-Behmel syndrome is characterized by: polyhydramnios neonatal recurrent hypoglycemia 6 facial deformities, including cleft lip and palate 9, macrostomia, macroglossia and dental malocclusion 12 hepatosplenomegaly multicystic dysplasia of [radiopaedia.org]

• Malocclusion

  It is characterized by pre- and postnatal overgrowth with macrosomia, distinctive craniofacial features (macrocephaly with coarse face, macroglossia, hypertelorism, dental malocclusion, palatal abnormalities), supernumerary nipples, congenital heart defects [orpha.net]

  Simpson-Golabi-Behmel syndrome is characterized by: polyhydramnios neonatal recurrent hypoglycemia 6 facial deformities, including cleft lip and palate 9, macrostomia, macroglossia and dental malocclusion 12 hepatosplenomegaly multicystic dysplasia of [radiopaedia.org]

  Even among individuals with normal intelligence, speech delay occurs frequently and may be secondary to macroglossia and malocclusion (Rodriguez-Criado et al., 2005). [genedx.com]

• Increased Birth Weight

  Major clinical findings include early onset intractable epileptic encephalopathy with a burst-suppression pattern on EEG, generalized muscular hypotonia, structural brain abnormalities, macrocephaly and increased birth weight, joint contractures, coarse [zora.uzh.ch]

  Growth: increased birth weight and height; prenatal/ postnatal overgrowth; broad, stocky, “bulldog” appearance. [accessanesthesiology.mhmedical.com]

• Hypertelorism

  Specific craniofacial phenotypic findings include hypertelorism, a large mouth with macroglossia, cleft palate or cleft lip, and a midline groove extending from philtrum to chin. [journals.sagepub.com]

  The infantile lethal form of SGBS is sometimes known as SGBS type 2. [1] [2] People with SGBS typically have distinctive facial features, including a large distance between the eyes ( hypertelorism ), an unusually wide mouth ( macrostomia ) with a large [rarediseases.info.nih.gov]

  Features: Head And Neck Macrocephaly With Characteristic Facies Ears Ear Pits Tags Or Creases Eyes Downslanting Palpebral Fissures Exophthalmos Hypertelorism Mouth And Oral Structures Macroglossia With Short Frenulum Widely Open Mouth Thick Lips Grooved [neo-genetics.com]

  The boy had distinctive coarse facial features, widely spaced eyes (ocular hypertelorism), a large tongue (macroglossia), abnormal ears and abnormalities affecting the roof of the mouth (the palate). [abstracts.eurospe.org]

  Autopsy findings for both male fetuses revealed increased growth parameters, hypertelorism, congenital diaphragmatic hernia and some features not commonly observed in SGB syndrome: small omphalocele, renal anomaly and ovotestes. [ashg.org]

• Average Intelligence

  Most individuals with SGBS are of average intelligence, although some degree of mental impairment has been observed in males who are more severely affected. [encyclopedia.com]

• Based on expert opinion, workup for tall stature that exceeds the individual's mid-parental height should include assessment of growth velocity and should consider full blood counts, complete biochemical analysis, IGF-I, IGFBP-3, free T4, and TSH, [frontiersin.org]

• Hepatocellular Carcinoma

  […] of Hepatocellular Carcinoma Researchgate:Source Turkish journal of oncology Serum Glypican-3, Vascular Endothelial Growth Factor, and Interleukin-6 Levels in Hepatocellular Carcinoma 10.5505:tjo.2018.1742 [cloud-clone.com]

  Wang XY, et al., Glypican-3 expression in hepatocellular tumors: diagnostic value for preneoplastic lesions and hepatocellular carcinoma. Human Pathol., 37(11): 1435 -41. 2006. 4. [biocare.net]

  Glypican 3 immunostaining with BioMosaic antibody (clone 1G12) has utility for differentiating hepatocellular carcinoma (HCC) and dysplastic changes in cirrhotic livers; HCC stains with GPC3, while cirrhotic liver does not. [biomosaics.com]

  Jakubovic and Serge Jothy, Glypican-3: From the mutations of Simpson–Golabi–Behmel genetic syndrome to a tumor marker for hepatocellular carcinoma, Experimental and Molecular Pathology, 82, 2, (184), (2007). Anne M. [doi.org]

  The glypican 3 oncofetal protein is a promising diagnostic marker for hepatocellular carcinoma. [ppmx.com]

A team of doctors is often needed to figure out the treatment options based on each person’s symptoms. Last updated: 5/10/2018 [rarediseases.info.nih.gov]

The material is in no way intended to replace professional medical care by a qualified specialist and should not be used as a basis for diagnosis or treatment. [orpha.net]

Eyes Standard treatment for strabismus and cataracts Hearing Standard treatment for hearing loss Congenital heart defects & conduction abnormalities Standard treatment as per cardiologist Hypospadias/cryptorchidism in males Standard treatment as per urologist [ncbi.nlm.nih.gov]

Prognosis Prognosis depends on the severity of the disease; in the most severe cases, SGBS is life-threatening before birth or in infancy, whereas in milder cases patients often live into adulthood. [orpha.net]

We conclude that the recurrent PIGA germline mutation c.1234C>T leads to a recognizable clinical phenotype with a poor prognosis and is the cause of SGBS2. [zora.uzh.ch]

We propose that Marden-Walker syndrome is one of the etiologic possibilities in children with the heterogeneous fetal a(hypo)kinesia deformation sequence (FADS). Differential diagnosis is discussed. The etiology is probably heterogeneous. [onlinelibrary.wiley.com]

Etiology SGBS is due to loss-of-function mutations in the GPC3 gene (Xq26), encoding Glypican-3 (GPC3), a cell surface heparin sulfate proteoglycan which acts as a negative regulator of Hedgehog (Hh) signaling during development. [orpha.net]

The exact role of GPC3 in the etiology of SGBS is still unknown. [atlasgeneticsoncology.org]

Summary Epidemiology The birth prevalence is unknown. Approximately 250 cases have been reported to date. Clinical description SGBS manifests a broad clinical picture with varying degrees of severity. [orpha.net]

[…] surgical disease - Rare neurologic disease - Rare oncologic disease - Rare otorhinolaryngologic disease - Rare renal disease - Rare surgical thoracic disease Classification (ICD10): - Congenital malformations, deformations and chromosomal abnormalities - Epidemiological [csbg.cnb.csic.es]

Debaun, a pediatrician specializing in oncology and epidemiology, created a registry for patients diagnosed with SGBS. [medlexi.com]

Pathophysiology Overgrowth syndrome in relation to the GPC3 coding region. Most families map Xq26 (Type 1); however, one large pedigree maps to Xp22 (Type 2). Mutation in gene for glypican-3 (GPC3) located in the region of Xq26. [accessanesthesiology.mhmedical.com]

Potential mechanisms contributing to the pathophysiology of post-acute COVID-19 include: (1) virus-specific pathophysiologic changes; (2) immunologic aberrations and inflammatory damage in response to the acute infection; and (3) expected sequelae of [nature.com]

CMS are a genotypically and phenotypically heterogeneous group of disorders, which share an underlying pathophysiology of impaired neuromuscular junction transmission [2]. [link.springer.com]

Missense mutations are rare and the two which were functionally characterized, impaired GPC3 function by preventing GPC3 cleavage and cell surface addressing respectively. [ibrain.univ-tours.fr]

For long term storage store at -20C in small aliquots to prevent freeze-thaw cycles. [avivasysbio.com]

Our data demonstrate that epitope-optimization is required to potently activate AFP- and GPC3- specific CD8 T cells, generating effective antitumor effect to prevent carcinogen-induced HCC in mice. [jimmunol.org]