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]

Patients may present with broad hands and feet with shortened and wide toes and fingers. [medlexi.com]

Physicians experienced in the clinical diagnosis of overgrowth syndromes may easily distinguish between these conditions for patients with a classical presentation, but some patients may have mild or atypical presentations. [nature.com]

• Coarse Facial Features

  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]

  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. [scielo.org.za]

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

• 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]

  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]

• Fishing

  Note: (1) CMA cannot determine the location or orientation of a duplication. (2) If a deletion or duplication is of sufficient size, fluorescence in situ hybridization ( FISH ) can be used to test parental samples for inheritance of the deletion or duplication [ncbi.nlm.nih.gov]

  X-linked syndromic 7 Microcephaly micropenis convulsions Craniorachischisis Verloes Bourguignon syndrome Spondyloepimetaphyseal dysplasia Strudwick type Hyperprolinemia type 2 Ethylmalonic encephalopathy Bilateral perisylvian polymicrogyria Oguchi disease Fish-eye [checkrare.com]

• High-Pitched Cry

  Hypotonia, absent primitive reflexes, a neonatal high-pitched cry, seizures, and EEG abnormalities have been reported. [invitae.com]

  Hypotonia and absent primitive reflexes, a high-pitched cry in neonates, seizures, and abnormal EEG have all been described. Hydrocephalus, epilepsy, and attention deficit hyperactivity disorder may also be present [ Tenorio et al 2014 ]. [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]

• Macrostomia

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

  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]

  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]

• Hip Dislocation

  dislocation / dysplasia / coxa valga / coxa vara / coxa plana - Hypospadias / epispadias / bent penis - Hypotonia - Intellectual deficit / mental / psychomotor retardation / learning disability - Micropenis / small penis / agenesis - Neoplasms / tumors [csbg.cnb.csic.es]

  Infants may have difficulty feeding, show signs of shallow breathing and be prone to dislocation of hip, dislocation of jaw, and neck dislocations. Hypotonia can be an indicator of SGBS as well as other congenital diseases. [medlexi.com]

  Skeletal Skeletal anomalies include advanced bone age, vertebral fusion, scoliosis, pectus excavatum, rib anomalies, winged scapula, congenital hip dislocation, small sciatic notches, and flared iliac wings. [invitae.com]

  Skeletal anomalies can include vertebral fusion, scoliosis, rib anomalies, and congenital hip dislocation. Hand anomalies can include large hands and postaxial polydactyly. [ncbi.nlm.nih.gov]

• Large Hand

  Digital anomalies include large hands, broad thumbs, brachydactyly, syndactyly, clinodactyly, and postaxial polydactyly. Striking index finger hypoplasia with congenital abnormalities of the proximal phalanx has been reported. [invitae.com]

  […] of the penis instead of at the tip (hypospadias) Testes that do not descend properly and are still inside the body (cryptorchidism) Skeletal Abnormalities of the hands and feet Broad thumbs Extra fingers or toes (polydactyly) Large hands Short fingers [rarediseases.org]

  Hand anomalies can include large hands and postaxial polydactyly. [ncbi.nlm.nih.gov]

• 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]

• Language Delays

  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]

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

• Neurologic Manifestation

  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. [ncbi.nlm.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]

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]

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]

The treatment of Simpson-Golabi-Behmel Syndrome is dependent on the type and severity of symptoms in the affected individual. [dovemed.com]

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]

What is the Prognosis of Simpson-Golabi-Behmel Syndrome? (Outcomes/Resolutions) The prognosis of Simpson-Golabi-Behmel Syndrome can be only determined based on the severity of the symptoms. [dovemed.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]

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]

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]

JAMA 307(23):2526–2533 Google Scholar Bellani G, Laffey JG, Pham T, Fan E, Brochard L, Esteban A, Gattinoni L, van Haren F, Larsson A, McAuley DF, Ranieri M, Rubenfeld G, Thompson BT, Wrigge H, Slutsky AS, Pesenti A, Investigators LS, Group ET (2016) Epidemiology [clintransmed.springeropen.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]

Prevention & Prophylaxis Due to Simpson-Golabi-Behmel syndrome being caused by a genetic defect, the only course of prevention is the testing of both the male and female parent prior to conception. [medlexi.com]

Most of the mutations that cause Simpson-Golabi-Behmel syndrome delete part or all of the GPC3 gene, which prevents cells from producing functional glypican 3. [ghr.nlm.nih.gov]

Currently, there are no specific methods or guidelines to prevent Simpson-Golabi-Behmel Syndrome, since it is a genetic condition Genetic testing of the expecting parents (and related family members) and prenatal diagnosis (molecular testing of the fetus [dovemed.com]