Paula and Bobby
Parents of Lillie
Mandibulofacial Dysostosis, Guion-Almeida Type (MFDGA)
What is Mandibulofacial Dysostosis, Guion-Almeida Type (MFDGA)?
This rare disease is a genetic syndrome that may also be referred to as Mandibulofacial Dysostosis with microcephaly.
It primarily affects the head and face. Speech and language delays and intellectual disability are common features of the condition.
There are just 60 cases of the syndrome reported worldwide to date.
This syndrome is also known as:
Growth And Mental Retardation, Mandibulofacial Dysostosis, Microcephaly, And Cleft Palate Mandibulofacial dysostosis - microcephaly Mandibulofacial Dysostosis With Microcephaly; Mfdm Mandibulofacialdysostosismicrocephaly Mandibulofacialdysostosiswithmicrocephaly MFD with microcephaly MFDwithmicrocephaly
What gene changes cause Mandibulofacial Dysostosis, Guion-Almeida Type (MFDGA)?
Mutations in the EFTUD2 gene are responsible for causing the syndrome.
It is inherited in an autosomal dominant pattern although most cases are the result of a new mutation and the first case in a family.
In the case of autosomal dominant inheritance just one parent is the carrier of the gene mutation, and they have a 50% chance of passing it onto each of their children. Syndromes inherited in an autosomal dominant inheritance are caused by just one copy of the gene mutation.
In some cases, a genetic syndrome may be the result of a de-novo mutation and the first case in a family. In this case, this is a new gene mutation which occurs during the reproductive process.
What are the main symptoms of Mandibulofacial Dysostosis, Guion-Almeida Type (MFDGA)?
One of the main features of this syndrome is a small head which appears to get smaller as the rest of the body grows normally.
Facial features or abnormalities characteristic of the syndrome include underdevelopment of the cheekbones and the middle of the face. A small jaw, small ears, and abnormal skin growths on the ears are also unique to the syndrome.
Hearing loss is common due to defects affecting the inner bones of the ears. A short stature and thumb abnormalities are other physical symptoms related to the syndrome.
Other consistent symptoms associated with the syndrome include growth and mental retardation
Possible clinical traits/features:
Autosomal dominant inheritance, Preaxial hand polydactyly, Slender finger, Seizure, Autosomal recessive inheritance, Overfolded helix, Large earlobe, Preauricular skin tag, Trismus, Trigonocephaly, Sensorineural hearing impairment, Proximal placement of thumb, Microcephaly, Respiratory difficulties, Ventricular septal defect, Telecanthus, Upslanted palpebral fissure, Midface retrusion, Short stature, Delayed speech and language development, Global developmental delay, Cognitive impairment, Low-set, posteriorly rotated ears, Low-set ears, Mandibulofacial dysostosis, Micrognathia, Microtia, Neurological speech impairment, Short nose, Anteverted nares, Epicanthus, Esophageal atresia, Feeding difficulties in infancy, Atresia of the external auditory canal, Deep philtrum, Malar flattening, Downslanted palpebral fissures, Conductive hearing impairment, Atrial septal defect, Abnormality of the antihelix, Cleft palate, Choanal atresia, Abnormality of the tragus
How does someone get tested for Mandibulofacial Dysostosis, Guion-Almeida Type (MFDGA)?
The initial testing for Mandibulofacial Dysostosis, Guion-Almeida Type syndrome 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.
Based on this clinical consultation with a geneticist, the different options for genetic testing will be shared and consent will be sought for further testing.
Medical information on Mandibulofacial Dysostosis, Guion-Almeida Type (MFDGA)
The distinguishing features of Mandibulofacial Dysostosis, Guion-Almeida Type (MFDGA) are malar and maxillary hypoplasia, auditory canal malformations with associated hearing loss, microcephaly, developmental delay, and characteristic facial features. Extracraniofacial malformations include esophageal atresia and congenital heart disease. MFDGA is caused by heterozygous mutations or deletions in the EFTUD2 gene.
MFDGA is a multisystem disorder that is caused by abnormal development of the first and second branchial arches. Malar and mandibular hypoplasia is a defining feature, including the resulting micrognathia and distinctive facial features (microtia, midface hypoplasia, broad nasal bridge, bulbous nasal tip).
Facial asymmetry, cleft palate, choanal atresia and preauricular tags are also commonly seen.
Hearing loss is present in the majority of patients and results from malformed ear development. Small/dysplastic pinna, auditory atresia/stenosis, vestibular system abnormalities and ossicular abnormalities are common.
Developmental delay and intellectual disability have been reported in the vast majority of patients with MFDGA, but vary in degree of severity. On average, patients with MFDGA started walking independently and talking at about 26 months (Huang et al., 2016). Microcephaly is nearly universal.
Seizures are present in approximately 20% of cases (Matsuo et al., 2017).
Thumb anomalies, heart defects and esophageal atresia/tracheoesophageal fistula are each seen in approximately one-third of patients. Short stature has also been reported.
Three unrelated children were reported by Wieczorek et al., (2009) with similar features but different from Treacher Collins syndrome. The cardinal features were small (sometimes dysplastic) ears, conductive hearing loss (canal stenosis, middle are abnormalities), choanal stenosis, preauricular tags, microcephaly and developmental delay. No mutations in TCOF1, CHD7 or HOXA2 were found.
Lehalle et al., (2014) described the clinical and molecular characteristics of 36 individuals with mandibulofacial dysostosis with microcephaly. All patients had either mutations or deletions in the EFTUD2 gene. In order of frequency, clinical characteristics include mandibular hypoplasia, external ear anomalies, psychomotor delay, malar hypoplasia, hearing loss, semicircular canal anomalies, microcephaly (mainly prenatal onset), auditory canal stenosis, facial asymmetry, esophageal atresia, congenital heart defect, preauricular tags, choanal atresia and cleft palate.
Four patients with heterozygous EFTUD2 mutations or deletions/duplications were found by Vincent et al., (2015) in a cohort of patients with a clinical diagnosis of Treacher Collins. All patients had microcephaly, intellectual disability, malar and mandibular hypoplasia, and deafness. All were in the atypical Treacher Collins group.
Sarkar et al., (2015) reported two male patients with de novo novel mutations in the EFTUD2 gene, one missense and one protein-truncating. Both patients had clinical characteristics described for mandibulofacial dysostosis, and some of the ear and auditory characteristics overlapped with CHARGE syndrome. Additional features in both patients included short stature.
Huang et al., (2016) described the clinical and molecular characteristics of 107 individuals from 94 kindreds. Clinical characteristics and demographics were similar as those reported by Lehalle et al., (2014). Molecular characteristics were 76 distinct mutations and seven microdeletions. Mutation origin was de novo in 75%, dominantly inherited in 19% and due to proven germline mosaicism in 6%.
Rengasamy Venugopalan et al., (2017) reported a female patient with an overlapping phenotype between Mandibulofacial Dysostosis and Oculo-Auriculo-Vertebral Spectrum. She had a heterozygous protein-truncating mutation in the EFTUD2 gene. Clinical characteristics included microcephaly, learning disability, gross facial asymmetry, micrognathia, airway obstruction, choanal atresia, left ear microtia, bilateral absence of ear canals, conductive hearing loss and speech articulation problems.
* This information is courtesy of the L M D.
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