Paula und Bobby
Eltern von Lillie
Was ist Muenke syndrome?
It is a rare genetic syndrome which leads to the premature closing of bones in the skull as an infant develops (craniosynostosis). This in turn leads to unique facial features affecting the head and face. As a syndrome it accounts for around 4% of all the recorded cases of craniosynostosis.
This syndrome is also known as:
FGFR3 craniosynostosis Muenke craniosynostosis Muenke Nonsyndromic Coronal Craniosynostosis Severe achondroplasia - developmental delay-acanthosis nigricans
Was Genveränderungen verursachen Muenke syndrome?
Veränderungen im FGFR3-Gen sind für die Auslösung des Syndroms verantwortlich.
Das Syndrom wird autosomal-dominant vererbt.
Was sind die wichtigsten symptome von Muenke syndrome?
Craniosynostosis (the premature closing of specific bones of the skull as the skull develops) is the main symptom of the syndrome. Generally in those affected by the syndrome this premature closing occurs along the line over the head between each ear. This in turn leads to an abnormally shaped head as well as wide set eyes and flat cheekbones. In some cases, although very few, individuals may have a larger head.
Other symptoms associated with the syndrome vary between individuals in terms of their presentation and severity, and in some cases individuals may have limited or no symptoms. Some individuals experience mild anomalies affecting the hands or feet. Others experience hearing loss. Developmental and learning difficulties or delays are reported in some cases.
Possible clinical traits/features:
Autosomal dominant inheritance, Sensorineural hearing impairment, Plagiocephaly, High palate, Hydrocephalus, Short toe, Short middle phalanx of finger, Cognitive impairment, Global developmental delay, Hypertelorism, Low anterior hairline, Intellectual disability, Abnormality of body height, Increased intracranial pressure, Capitate-hamate fusion, Thimble-shaped middle phalanges of hand, Broad hallux, Abnormal palate morphology, Brachycephaly, Coronal craniosynostosis, Downslanted palpebral fissures, Malar flattening, Brachydactyly, Cone-shaped epiphyses of the phalanges of the hand, Cone-shaped epiphysis, Clinodactyly, Proptosis, Ptosis, Midface retrusion, Short middle phalanx of toe, Macrocephaly, Synostosis of carpal bones, Tarsal synostosis, Radial deviation of finger
Wie wird jemand getestet? Muenke syndrome?
Die ersten Tests für Muenke syndrome kann mit einem Gesichtsanalyse-Screening beginnen, durch die FDNA Telehealth Telegenetik-Plattform, die die Schlüsselmarker der syndrom und skizzieren Sie die Notwendigkeit weiterer Tests. Es folgt ein Beratungsgespräch mit einem genetischen Berater und dann einem Genetiker.
Basierend auf dieser klinischen Konsultation mit einem Genetiker werden die verschiedenen Optionen für Gentests geteilt und die Zustimmung für weitere Tests eingeholt.
Medizinische Informationen zu Muenke syndrome
Bellus et al., (1996) reported a specific mutation in the fibroblast growth factor receptor (FGFR3) gene at 4p16 giving a variable picture of craniosynostosis in different individuals. The mutation was at C749G predicting a Pro250Arg amino acid substitution in the extracellular domain between the second and third immunoglobulin-like loops. This is in an analogous position to the Pfeiffer mutation in FGFR1 and the Apert mutation in FGFR2. Affected individuals had a phenotype ranging from non-syndromic craniosynostosis through Crouzon syndrome to mild Pfeiffer syndrome or even a Saethre-Chotzen type phenotype.
Moloney et al., (1997) studied 26 patients with non-syndromic coronal craniosynostosis and found that 8 carried the Pro250Arg mutation of the FGFR3 gene. 61 individuals from 20 unrelated families were reported with the Pro250Arg mutation by Muenke et al., (1997). This included the family reported under craniosynostosis, Adelaide type (qv). Reardon et al., (1997) reported further cases with this mutation and emphasise the variability of the phenotype. Golla et al., (1997) reported a further family. One individual had a severe clover-leaf skull.
Further clinical features of the condition were reviewed by Graham et al., (1998). Gripp et al., (1998) studied 37 patients with unicoronal craniosynostosis and found the mutation in 4. In three cases one parent was found to carry the mutation with an extremely mild phenotype. Paznekas et al., (1998) also emphasise that cases of this mutation can have a Saethre-Chotzen phenotype.
Lajeunie et al., (1999) presented evidence suggesting that females were more severely affected than males with this mutation. Tavormina et al., (1999) studied four individuals with a bone dysplasia resembling thanatophoric dysplasia, but with survival in three cases who developed acanthosis nigricans. An FGFR3 mutation (A1949T; Lys650Met) adjacent to a thanatophoric dysplasia type II mutation was found. Further clinical details of these cases are provided by Bellus et al., (1999).
Lowry et al., (2001) reported a dominant family where at least 5 individuals in 3 generations had craniosynostosis associated with Klippel-Feil anomaly and Sprengel shoulder. An FGFR3 Pro250Arg mutation was found in all affected individuals. However, they also reported an isolated case with a similar combination who did not have this mutation. Roscioli et al., (2001) reported a father and daughter with craniosynostosis and an FGFR3 Pro250Arg mutation. However, in the daughter, there were cutis gyrata of the palm and a linear maculopapular lesion of the forearm consistent with acanthosis nigricans. Iwata et al., (2001) created a mouse model.
Schindler et al., (2002) reported a mother and child with isolated craniosynostosis where a P250L mutation of the FGFR3 gene was demonstrated. Grosso et al., (2003) reported a case with bilateral dysgenesis of medial temporal lobe structures (inadequate differentiation between white and grey matter, defective gyri, and an abnormally shaped hippocampus). They were mentally normal but had early-onset temporal lobe-related seizures. Two sibs and their mother had Pro250 to Arg mutations (Sabatino et al., 2004). The mother had the facial features (hypertelorism, down-slanting palpebral fissures) but no evidence of craniosynostosis.
All 10 sporadic cases reported by Rannan-Eliya et al., (2004) had the mutation from father's sperm (paternal origin). Two sibs and their mother had Pro250 to Arg mutations (Sabatino et al., 2004). The mother had the facial features (hypertelorism, down-slanting palpebral fissures) but no evidence of craniosynostosis.
The condition is well reviewed by Doherty et al., (2007). They comment on the high frequency of mild to moderate low-frequency sensory hearing loss and feeding and swallowing difficulties in childhood.
A further case with an FGFR3 Lys650Met mutation was detected prenatally (Zankl et al., 2008). Death occurred before 6 months of age. Significant phenotypic variability in identical twins, discordant for heart defects, a TOF, and hydrocephaly/porencephaly was noted by Escobar et al., (2009).
Note the case with features of both achondroplasia and thanatophoric dysplasia with a G375C FGFR3 mutation (Barton et al., 2010). Hemimegalencephaly has also been reported (Abdel-Salem et al., 2011). Note too that patients with this condition might be sensitive to hypervitaminosis A and are at higher risk for developing post-surgery hydrocephalus (Agochukwu et al., (2011).
10 individuals out of 65 unrelated cases with craniosynostosis with or without limb involvement were found with the Pro250Arg mutation. Most affected individuals had normal appearing hands and feet however on radiographs short and broad middle phalanges, carpal and tarsal fusion, and cone-shaped epiphyses were noted. Indeed, 25% have talocalcaneal coalition (Agochukwu et al., (2013).
A patient with severe platyspondyly and a Ser344Cys FGFR3 mutation was reported by Takagi et al., (2015).
Kruszka et al. (2016) reported on 106 individuals from 71 families with Muenke syndrome. In 64.7% of the patients, the mutation was inherited. Craniosynostosis was present in 85% of the cases. Hearing loss was identified in 70.8%, developmental delay in 66.3%, intellectual disability in 35.6%, attention deficit hyperactivity disorder in 23.7%, and seizures in 20.2%. In individuals with complete skeletal surveys, 75% were found to have at least a single abnormal radiographic finding in addition to craniosynostosis (bone fusion, brachydactyly, clinodactyly, broad thumbs and toes). Clefting was observed in 1.1% of the patients.
González-del ángel et al. (2016) described eight patients with heterozygous p.Pro250Arg mutation in the FGFR3 (form a cohort of 56 patients with non-syndromic uni- or bicoronal craniosynostosis). Clinical characteristics included bicoronal (six patients) or unicoronal (two patients) synostosis requiring surgical repair, midface hypoplasia, down-slanting palpebral fissures, hypertelorism, facial asymmetry, developmental delay, brachydactyly, and thimble-like middle phalanges in hands and feet.
* This information is courtesy of the L M D.
If you find a mistake or would like to contribute additional information, please email us at: [email protected]
Erhalten Sie eine schnellere und genauere Genetische Diagnostik!
Mehr als 250,000 Patienten erfolgreich analysiert!
Warten Sie nicht Jahre auf eine Diagnose. Handeln Sie jetzt und sparen Sie wertvolle Zeit.
Was ist FDNA Telehealth?
FDNA Telehealth ist ein führendes Unternehmen für digitale Gesundheit, das einen schnelleren Zugang zu genauen genetischen Analysen bietet.
Mit einer von führenden Genetikern empfohlenen Krankenhaustechnologie verbindet unsere einzigartige Plattform Patienten mit Genexperten, um ihre dringendsten Fragen zu beantworten und eventuelle Bedenken hinsichtlich ihrer Symptome zu klären.
Vorteile von FDNA Telehealth
Unsere Plattform wird derzeit von über 70% der Genetiker verwendet und wurde zur Diagnose von über 250,000 Patienten weltweit eingesetzt.
FDNA Telehealth bietet innerhalb von Minuten eine Gesichtsanalyse und ein Screening, gefolgt von einem schnellen Zugang zu genetischen Beratern und Genetikern.
Unser nahtloser Prozess beginnt mit einer ersten Online-Diagnose durch einen genetischen Berater, gefolgt von Konsultationen mit Genetikern und Gentests.
Genauigkeit & Präzision
Erweiterte Funktionen und Technologien für künstliche Intelligenz (KI) mit einer Genauigkeitsrate von 90% für eine genauere genetische analyse.
Schnellerer Zugang zu genetischen Beratern, Genetikern, Gentests und einer Diagnose. Falls erforderlich, innerhalb von 24 Stunden. Sparen Sie Zeit und Geld.
Privatsphäre & Sicherheit
Wir garantieren den größtmöglichen Schutz aller Bilder und Patienteninformationen. Ihre Daten sind immer sicher und verschlüsselt.