Paula et Bobby
Parents de Lillie
Simpson-Golabi-Behmel syndrome, Type 1
Qu'est-ce que Simpson-Golabi-Behmel syndrome, Type 1?
It is a rare genetic syndrome that affects multiple parts of the body. The syndrome occurs mainly in males due to its mode of inheritance. The syndrome is an overgrowth syndrome, meaning it triggers excessive growth both before birth and after.
This syndrome is also known as:
Quelles sont les causes des changements génétiques Simpson-Golabi-Behmel syndrome, Type 1?
Changes to the GPC3 gene are responsible for causing the syndrome.
It is an X-linked syndrome meaning that the mutated gene responsible for causing the syndrome is located on the X chromosome. This is why the syndrome is more common and severe in males, who have just one X chromosome. Females, with two x chromosomes receive just one copy of the altered gene and are thus less likely to be affected.
Quels sont les principaux symptômes de Simpson-Golabi-Behmel syndrome, Type 1?
Overgrowth is the main symptom of this rare disease. But the syndrome also presents with unique facial features including widely spaced eyes, a large mouth and tongue, broad nose and anomalies with the palate of the mouth. Another name for these facial features is coarse features.
The syndrome also affects the chest and abdomen. Some individuals are born with extra nipples, an opening in the muscle that covers the abdomen and one of several types of hernias.
Other health conditions associated with the syndrome include heart defects, larger than average kidneys, enlarged liver and spleen and abnormalities relating to the skeletal system.
In some cases individuals develop either cancerous or non cancerous tumors. Specifically Wilms tumor, which is a rare type of kidney cancer.
Possible clinical traits/features:
Arrhythmia, 2-3 finger syndactyly, Abnormal form of the vertebral bodies, Tall stature, Intestinal malrotation, Inguinal hernia, Low-set, posteriorly rotated ears, Macroglossia, Lung segmentation defects, Pancreatic islet-cell hyperplasia, Short nose, Neurological speech impairment, Anteverted nares, Narrow sacroiliac notch, Short greater sciatic notch, Nephroblastoma, Neuroblastoma, Mandibular prognathia, Meckel diverticulum, Pectus excavatum, Multicystic kidney dysplasia, Preauricular pit, Muscular hypotonia, Toe syndactyly, Patent ductus arteriosus, Preauricular skin tag, Omphalocele, Polysplenia, Postaxial hand polydactyly, Wide mouth, Webbed neck, Short neck, Renal cyst, Seizure, Abnormality of the helix, Abnormal fingernail morphology, Accelerated skeletal maturation, Aplasia/Hypoplasia of the corpus callosum, Aplasia/Hypoplasia of the abdominal wall musculature, Wide nasal bridge, Broad foot, Cardiomyopathy, Broad toe, Broad thumb, Broad secondary alveolar ridge, Broad palm, Polyhydramnios, Cerebellar
Comment quelqu'un se fait-il tester pour Simpson-Golabi-Behmel syndrome, Type 1?
The initial testing for Simpson-Golabi-Behmel syndrome, Type 1 can begin with facial analysis screening, through the FDNA Telehealth telegenetics platform, which can identify the key markers of the syndrome and outline the need for further testing. A consultation with a genetic counselor and then a geneticist will follow.
Informations médicales sur Simpson-Golabi-Behmel syndrome, Type 1
This neonatal overgrowth syndrome is characterized by a large head with coarse features, thickened lips, a wide mouth, a large tongue, a husky voice, a high-arched palate, malposition of the teeth, a prominent jaw, a short neck and hepatosplenomegaly. In the cases reported by Behmel et al., (1984) intelligence was normal in one brother but low in the other brother. One of the brothers had a unilateral post-axial polydactyly, as did his male first cousin. Both brothers had bilateral cryptorchidism. Three brothers all with cryptorchidism were reported by Griffith et al., (2009).
Simpson et al., (1975) described two male maternal cousins from an Ashkenazi Jewish pedigree. They both had a broad stocky appearance, a large protruding jaw and maxilla, a widened nasal bridge, upturned nasal tip, an enlarged tongue, broad short hands and fingers, and normal intelligence. As infants the facies were sufficiently coarse that a diagnosis of hypothyroidism was considered.
Golabi and Rosen (1984) reported an X-linked overgrowth syndrome associated with severe mental retardation and, frequently, early death. There was prenatal macrosomia and postnatal enlargement of the liver and spleen. One child had a large head. Facially there was hypertelorism, a short broad nose, a large mouth and a vertical groove which involved the philtrum, the lower lip and chin, and the tongue. Meckel diverticulum and large cystic kidneys occurred, but were not constant features. An unusual coccygeal skin tag was reported, as well as hypoplasia of the distal phalanges. Post-axial polydactyly occurred once. All four children in the Golabi and Rosen (1984) paper had a cleft palate, which was submucous in some. Most authors now feel that all three case reports represent the same condition (eg Neri et al., 1988; Opitz et al., 1988). Diaphragmatic hernia may also be a feature of the condition (Chen et al., 1993). Hypoplastic fingernails, particularly of the index fingers, seem to be a characteristic feature. Day and Fryer (2004) reported a case with marked hypoplasia of the index fingers (also an abnormality of the proximal phalanx) and point out that index finger abnormalities in this condition are not uncommon. Kim et al., (1999) reported a male with the condition who had a choledochal cyst. He was part a family previously reported by Chen et al., (1993) and Golabi and Rosen (1984). Savarirayan and Bankier (1999) reported two brothers with the condition who had attention deficit hyperactivity disorder, and the patient of Young et al., (2006) was mentally handicapped, had seizuresand hydrocephalus. He had prominent, anteverted ears.
Terespolsky et al., (1995) reported a family where five males had an apparently severe form of the condition presenting with hydrops and with hypotonia and neurological impairment in survivors. Hughes-Benzie et al., (1994) reported a case presenting in pregnancy where there was raised maternal serum alpha-fetoprotein level at 16 weeks. Swallowing difficulties and bronchiectasis were features in the child reported by Glamuzina et al., (2009).
Verloes et al., (1995) reported a male infant who died in the neonatal period with overgrowth, macroglossia, ambiguous genitalia, a diaphragmatic hernia, visceromegaly, multicystic renal dysplasia, Langerhans islet hyperplasia, nephroblastomatosis, adrenal adenomas and dysplastic testes. The difficulty in the differential diagnosis between Perlman, Beckwith-Wiedemann, and Simpson-Golabi-Behmel syndromes was discussed. Coppin et al., (1997) reported a further case with similar overlap. The family reported by Stratakis et al., (2001) mostly likely had this condition. A patient reported by Cureton et al., (2007) had a hepatic vascular malformation. Knopp et al., (2015) showed a case with an initial diagnosis of Beckwith-Wiedemann who 21 years had to be reassigned to SGBS. Important points were that the facial features evolved and intelligence is better preserved.
Cole (1998) provides a good review of overgrowth syndromes and the overlap between Beckwith-Wiedemann syndrome and Simpson-Golabi-Behmel syndrome. A patient (with a GPC3 mutation) had craniosynostosis, penoscrotal hypospadias and a large prostatic utricle (Villarreal et al., 2013).
Hughes-Benzie et al., (1992) mapped the gene to Xq13-q21 and pointed out a possible association with embryonal tumours, particularly Wilms', neuroblastoma and perhaps hepatoblastoma - the same authors have emphasized the similarities with Beckwith syndrome (Hughes-Benzie et al., 1992). Lapunzina et al., (1998) reported a male case with a hepatocellular carcinoma. Xuan et al., (1994) and Orth et al., (1994) remapped the condition to Xq25-q27. Punnett (1994) reported a female with a balanced X;1 translocation (Xq26;1q12) which provided additional evidence of a localisation between Xq25 and Xq27. Pilia et al., (1996) demonstrated deletions in the GPC3 gene which codes for a putative extracellular proteoglycan, glypican 3 that appears to form a complex with insulin-like growth factor 2 (IGF2). Selleck (1999) reviews the mechanism of action of proteoglycans and glypican in particular. The GPC3 gene was also disrupted in two female cases with balanced translocations. One of these cases was originally diagnosed as having Klippel-Feil syndrome, because of multiple cervical vertebral fusions. Lindsay et al., (1997) found deletions of the gene GPC3 in 5 out of 18 families with the condition. Veugelers et al., (2000) studied 10 patients and identified mutations in seven (one deletion of a GPC3 exon, one frameshift, three nonsense, and one splice mutation). No mutations in the GPC4 gene were found in the remaining patients. Weksberg et al., (1996) provide a good review. Hughes-Benzie et al., (1996) and Neri et al., (1998) provide a good review of genotype/phenotype correlations. Germinal mosaicism was the likely reason for the two affected brothers with mutations that could not be found in their mother (Romanelli et al., 2007).
A paper by Gurrieri et al., (2011) tells the exraordinary story of a family (with a mutation) that could be traced back to a macrosomic fetus in a glass jar in a university museum, who had the same mutation. Duplications of exon 1-9 of glypican-4 (GPC4) has been found in the original Golabi and Rosen (1984) family - Waterson et al., (2010). A patient, who had in addition a hepatoblastoma had a duplication of exons 2-4 of the GPC3 gene (Mateos et al., 2013). Another exon 2 deletion was reported by Cottereau et al., (2014).
Halayem et al., (2015) reported a patient with Simpson-Golabi-Behmel syndrome and a confirmed deletion of 6–8 exons of GPC3. Polyhydramnios and kidney enlargement were noted prenatally. Birth weight, length and head circumference were above the 90th percentile. The facial features included coarse face, macrocephaly, hypertelorism, broad nasal bridge, macrostomia, and macrognathia. Hepatomegaly, splenomegaly, pyelectasis, inguinal hernia, umbilical hernia, thoracolumbar kyphosis, broad and short hands with broad fingertips were also present. Central nervous system abnormalities included a persistent craniopharyngeal canal and left temporo-polar arachnoid cyst. The boy had epilepsy and obstructive sleep apnea. He also showed behavioural regression, aggressive outbursts, oppositional disorder and an obsessive behaviour.
Vaisfeld et al., (2016) described a female with a de novo deletion of exon 1 in in GPC3 with full clinical expression of the disease phenotype. X chromosome inactivation studies showed 33-67% and 20-80% ratio for skin fibroblasts and peripheral blood leukocytes, respectively.
Vuillaume et al., (2018) analyzed 120 unrelated families with Simpson-Golabi-Behmel syndrome. The authors described 86 distinct GPC3 gene mutations. Majority of the mutations were deletions or truncating mutations predicted to result in a loss-of-function. Missense mutations were rare.
* This information is courtesy of the L M D.
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