Presentation
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]
Entire Body System
- 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]
- Asymptomatic
Female carriers are usually asymptomatic, but some are noted to have mild features detected following detailed clinical assessment after diagnosis in a male relative. [nature.com]
Carrier females are often asymptomatic, though females may also exhibit features of SGBS1. Genetic testing of GPC3 may confirm a diagnosis and help guide treatment and management decisions. [invitae.com]
Female carriers are most likely asymptomatic, whereas all male individuals are affected. With the advances in prenatal diagnosis within the last years, diagnosis of SGBS has been described but only in single cases. [mdpi.com]
Evaluation of relatives at-risk: It is appropriate to clarify the genetic status of apparently asymptomatic older and younger at-risk relatives of an affected individual by molecular genetic testing of the GPC3 or GCP4 pathogenic variant in the family [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]
Gastrointestinal
- 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]
Jaw & Teeth
- 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]
Musculoskeletal
- Macrocephaly
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]
Characteristic dysmorphic features include macrocephaly with coarse, distinctive facies with a large protruding jaw, broad nasal bridge and cleft palate. Cardiac defects are frequent. {ECO:0000269 PubMed:10814714}. [genecards.org]
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]
We report on 2 brothers with overgrowth, macrocephaly, polydactyly, supernumerary nipples, and characteristic facial appearance. In addition, the propositus also had pulmonic stenosis and a cleft palate. [ncbi.nlm.nih.gov]
Fetus
- Hydrops Fetalis
A lethal form of SGBS, known as SGBS type 2 (see this term) and characterized by hydrops fetalis, has also been described. [orpha.net]
fetalis, and death within first 8 weeks of life. [accessanesthesiology.mhmedical.com]
Xp22: lethal form, multiple anomalies, hydrops fetalis, death within first 8 weeks of life. [atlasgeneticsoncology.org]
- 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]
Neurologic
- Extrapyramidal Symptoms
Extrapyramidal Symptoms Scale Simpson-Angus Rating Scale Simpson-Angus Scale Simpson-Golabi-Behmel syndrome Simpson-Golabi-Behmel syndrome type 1 Simpson-Miller, Portia simpsonite Simpsons Simpsons Simpsons Simpsons Hit and Run Simpsons Multimedia Archiv [acronyms.thefreedictionary.com]
Extrapyramidal Symptoms Scale Simpson-Angus Rating Scale Simpson-Angus Scale Simpson-Golabi-Behmel syndrome Simpson-Golabi-Behmel syndrome Simpson-Golabi-Behmel syndrome type 1 Simpson-Miller, Portia simpsonite Simpsons Simpsons Simpsons Simpsons Hit [medical-dictionary.thefreedictionary.com]
Urogenital
- Cesarean Section
Patient 1 was a 7-year-old boy with non-consanguineous parents, born at 26 weeks of gestation by emergency cesarean section due to fetal distress. [nature.com]
Workup
• 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]
Other Pathologies
- 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]
Treatment
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 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]
Etiology
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]
Epidemiology
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
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]
Prevention
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]