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]

• 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]

• Multiple Congenital Anomalies

  OLS > Orphanet Rare Disease Ontolog ORDO > Orphanet:373 http://www.orpha.net/ORDO/Orphanet_373 Simpson-Golabi-Behmel syndrome (SGBS, also referred to as SGBS type 1) is a rare X-linked multiple congenital anomalies syndrome, characterized by pre- and [ebi.ac.uk]

  congenital anomalies, and early death ("MCAHS2"), (ii) neurodegenerative encephalopathy with systemic iron overload (ferro-cerebro-cutaneous syndrome, "FCCS"), and (iii) intellectual disability and seizures without dysmorphism. [zora.uzh.ch]

  congenital anomalies and mental retardation. [ncbi.nlm.nih.gov]

• 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]

• Surgical Procedure

  Anesthesia was maintained with 2% - 3% sevoflurane and supplemental IV fentanyl (total 40 μg), with spontaneous respiration maintained throughout the surgical procedure. [file.scirp.org]

  Anesthesia was maintained with only 3% sevoflurane, nitrous oxide and oxygen with spontaneous respiration throughout the surgical procedure. Difficulty in ventilation due to macroglossia was overcome by orophyrangeal airway. [oatext.com]

• Underweight

  'I know my body is emaciated but I still see a fat person in the mirror' I was first hospitalised for being underweight at 17. It kept happening - sometimes for up to three years at a time - until I was 30. [dailymail.co.uk]

• 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]

• 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]

• Chest Deformity

  Furthermore he had a chest deformation with two extra nipples. Puberty was normal. The bone age was about 16yrs. We excluded pediatric and endocrinological causes connected with overgrowth. [abstracts.eurospe.org]

  The additional clinical findings of short, broad hands, pectus excavatum chest deformities, and supernumerary nipples, present in both boys, adds further credibility to the diagnosis. [jmg.bmj.com]

  Due to this low muscle tone, there are several features that can result such as mouth breathing, a deformity of the chest wall (pectus excavatum), shoulders that droop, hernias, and undescended testicles. [encyclopedia.com]

  DISCUSSION The current patient displayed some typical clinical features of SGBS, including macrosomia at birth, distinctive craniofacial features, supernumerary nipples, chest deformity, heart conduction defects and hand anomalies. [sciendo.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]

• Psychomotor Retardation

  retardation / learning disability - Micropenis / small penis / agenesis - Neoplasms / tumors - Nephroblastoma / Wilms tumor - Neuroblastoma - Seizures / epilepsy / absences / spasms / status epilepticus - Structural anomalies of the pancreas - Talipes-varus [csbg.cnb.csic.es]

  © Munksgaard, 1993 The Marden-Walker syndrome is characterized by psychomotor retardation, a mask-like face with blepharophimosis, micrognathia and a high-arched or cleft palate, low-set ears, kyphoscoliosis and joint contractures. [onlinelibrary.wiley.com]

  retardation syndrome Autosomal recessive cerebellar ataxia-pyramidal signs-nystagmus-oculomotor apraxia syndrome Autosomal recessive cerebellar ataxia-saccadic intrusion syndrome Autosomal recessive cerebelloparenchymal disorder type 3 Autosomal recessive [se-atlas.de]

  […] noneruption of with maxillary hypoplasia and genu valgum Mosaic trisomy 14 Charcot-Marie-Tooth disease Charcot-Marie-Tooth disease Dystelephalangy Microphthalmia syndromic 8 Acheiropody Short stature deafness neutrophil dysfunction Aniridia renal agenesis psychomotor [checkrare.com]

• Short Nose

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

  A Short Nose With A Flat And Broad Bridge Thorax Supernumerary Nipples Rib Abnormalities Pectus Excavatum Coccygeal Tags Or Bony Appendages Skin Thickened Or Dark And Redundant Skin Cardiovascular System Bundle Branch Block Atrioventricular Block Dilated [neo-genetics.com]

  Individuals with this condition have increased height and weight for their age; a broad, stocky appearance; a large protruding jaw; a short, broad nose; incomplete closure of the roof of the mouth ( cleft palate ); and broad, short hands and fingers. [encyclopedia.com]

  Individuals with this condition have: increased height and weight for their age a broad, stocky appearance a large protruding jaw a short, broad nose incomplete closure of the roof of the mouth (cleft palate) broad, short hands and fingers. [chdbabies.com]

• Language Delays

  Language delay is common, and mental retardation varies from mild to severe, although individuals with normal intelligence have been reported. [preventiongenetics.com]

  Central nervous system The incidence of developmental delay is unclear. Most affected individuals have low-to-normal IQ scores, although intelligence can range from normal to moderate cognitive impairment with language delay being very common. [invitae.com]

  Normal intelligence has been described, but mild to severe intellectual disability is common, with language delay being the most characteristic finding. Neurologic manifestations are perhaps the most varied findings. [ncbi.nlm.nih.gov]

  Hypotonia, seen in 70% of patients, is believed to contribute to motor delays, expressed as difficulty with early feeding and walking (after 15 months). Hypotonia tends to improve with age, however delays in expressive language are frequently seen. [frontiersin.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]

• Hypoglycemia

  Furthermore, the patient had persistent hypoglycemia even when provided enteral nutrition in accordance with his age and weight. [journals.lww.com]

  Blood sugar level should be monitored and intravenous dextrose may be required to avoid hypoglycemia. The use of antibiotics for endocarditis prophylaxis must be considered. Beckwith-Wiedemann Syndrome:... [accessanesthesiology.mhmedical.com]

  As with other overgrowth syndromes, hypoglycemia may occur in the neonatal period, and hepatomegaly has been described (Neri et al., 1998). The risk for embryonal tumors is increased but is not well established. [genedx.com]

  Short And Broad Neck Muscles Hypotonia Nervous System Central Nervous System Abnormalities And Seizures Gastrointestinal System Hepatomegaly Malformations And Enlarged Pancreas Hematopoietic System Splenomegaly Hyperbilirubinemia, Polycythemia, And Hypoglycemia [neo-genetics.com]

  No episodes of hypoglycemia were noted as he was maintained on infusion with 0.45% dextrose normal saline overnight. [oatext.com]

• Visceromegaly

  […] macrosomia, distinctive craniofacial features (macrocephaly with coarse face, macroglossia, hypertelorism, dental malocclusion, palatal abnormalities), supernumerary nipples, congenital heart defects and arrhythmias, vertebral segmental defects, abdominal visceromegaly [orpha.net]

  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 [en.wikipedia.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]