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| '''Other Names:''' Mandibulofacial dysostosis, Guion-Almeida type; MFDGA; MFDM; Mandibulofacial dysostosis-microcephaly syndrome; Growth delay - intellectual disability - mandibulofacial dysostosis - microcephaly - cleft palate; MFDM syndrome; Growth delay-intellectual disability-mandibulofacial dysostosis-microcephaly-cleft palate syndrome
| | #REDIRECT [[Mandibulofacial dysostosis-microcephaly syndrome]] |
| Mandibulofacial dysostosis with microcephaly (MFDM) is a disorder characterized by [[developmental delay]] and abnormalities of the head and face.
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| =='''Epidemiology'''==
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| MFDM is a rare disorder; its exact prevalence is unknown. More than 60 affected individuals have been described in the medical literature.
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| =='''Cause'''==
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| MFDM is caused by mutations in the''' EFTUD2 gene'''. This gene provides instructions for making one part (subunit) of two complexes called the '''major and minor spliceosomes'''. Spliceosomes help process messenger RNA (mRNA), which is a chemical cousin of DNA that serves as a genetic blueprint for making proteins. The spliceosomes recognize and then remove regions called introns to '''help produce mature mRNA molecules'''.
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| EFTUD2 gene mutations that cause MFDM result in the production of''' little or no functional enzyme from one copy of the gene in each cell'''. A shortage of this enzyme likely '''impairs mRNA processing'''. The relationship between these mutations and the specific symptoms of MFDM is not well understood.
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| Inheritance
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| [[File:Autosomal dominant - en.svg|thumb|right|Autosomal dominant pattern, a 50/50 chance.]]
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| This condition is inherited in an [[autosomal dominant]] pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. Most cases result from new mutations in the gene and occur in people with no history of the disorder in their family. In other cases, an affected person inherits the mutation from a parent. The parent may be mildly affected or may be unaffected. Sometimes the parent has the gene mutation only in some or all of their sperm or egg cells, which is known as germline mosaicism. In these cases, the parent has no signs or symptoms of the condition.
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| =='''Signs and symptoms'''==
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| Mandibulofacial dysostosis with microcephaly (MFDM) may affect multiple parts of the body but primarily affects the head and face. People with MFDM are usually born with a small head ([[microcephaly]]) which does not grow at the same rate as the body. [[Intellectual disability]] ranges from mild to severe and is present in almost all affected people. Speech and language problems are also common.
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| Facial abnormalities in affected people may include underdevelopment ([[hypoplasia]]) of the midface and cheekbones; a small lower jaw ([[micrognathia]]); small and malformed ears; facial asymmetry; and [[cleft palate]]. Other head and facial features may include a metopic ridge; up- or downslanting [[palpebral fissures]]; a prominent [[glabella]] (space between the eyebrows); a broad nasal bridge; a bulbous nasal tip; and an everted lower lip. Abnormalities of the ear canal, ear bones, or inner ear often lead to hearing loss. Affected people can also have a blockage of the nasal passages ([[choanal atresia]]) that can cause respiratory problems. Other signs and symptoms in some people with MFDM may include [[esophageal atresia]], congenital heart defects, thumb anomalies, and/or short stature.
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| For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed.
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| 80%-99% of people have these symptoms
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| *Abnormality of the [[antihelix]]
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| *Absent [[tragus]]
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| *[[Cleft palate]](Cleft roof of mouth)
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| *Delayed speech and language development(Deficiency of speech development)
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| *Feeding difficulties(Feeding problems)
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| *[[Hypoplasia]] of the [[maxilla]](Decreased size of maxilla)
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| *[[Intellectual disability]](Mental deficiency)
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| *Low-set ears(Low set ears)
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| *Malar flattening(Zygomatic flattening)
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| *[[Micrognathia]](Little lower jaw)
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| *[[Microtia]](Small ears)
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| *Morphological abnormality of the middle ear(Middle ear malformation)
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| *Postnatal [[microcephaly]]
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| *Preauricular skin tag
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| *Short nose(Decreased length of nose)
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| *Short stature(Decreased body height)
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| *[[Trigonocephaly]](Triangular skull shape)
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| *Underdeveloped [[tragus]]
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| *Upslanted [[palpebral fissure]](Upward slanting of the opening between the eyelids)
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| 30%-79% of people have these symptoms
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| *Accessory oral [[frenulum]]
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| *[[Atresia]] of the external auditory canal(Absent ear canal)
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| *[[Epicanthus]](Eye folds)
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| *Large earlobe(Fleshy earlobe)
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| *Overfolded helix(Overfolded ears)
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| *Preaxial hand [[polydactyly]](Extra thumb)
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| *[[Telecanthus]](Corners of eye widely separated)
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| 5%-29% of people have these symptoms
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| *Atrial septal defect(An opening in the wall separating the top two chambers of the heart)
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| *Conductive hearing impairment([[Conductive deafness with malformed external ear|Conductive deafness]])
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| *Esophageal [[atresia]](Birth defect in which part of esophagus did not develop)
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| *Proximal placement of thumb(Attachment of thumb close to wrist)
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| *[[Seizure]]
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| *Ventricular septal defect(Hole in heart wall separating two lower heart chambers)
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| =='''Diagnosis'''==
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| Yes. [[Genetic testing]] is available for mandibulofacial dysostosis with [[microcephaly]] (MFDM) and confirms the diagnosis in virtually all people suspected of having MFDM. There are two approaches to genetic testing for this condition. One is [[sequence analysis]] of the '''EFTUD2 gene''' to identify a mutation (which detects ~91% of affected people), and the other is [[deletion analysis]] (which detects ~9%), for people in whom sequencing does not detect a mutation.
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| When a diagnosis of MFDM is strongly suspected but genetic testing is [[inconclusive]], a clinical diagnosis may still be appropriate. However, given the high sensitivity of genetic testing for this condition, other disorders with overlapping features should first be carefully considered.
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| =='''Treatment'''==
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| Individualized treatment of craniofacial features is managed by a multidisciplinary team which may include various specialists. [[Surgery]] may be needed for a variety of abnormalities, in the newborn period or beyond. Treatment of [[hearing loss]] is individualized, and may involve conventional [[hearing aids]], bone-anchored hearing aid, and/or [[Cochlear implant|cochlear implants]]. Occupational, physical, and/or speech/language therapies are involved as needed to optimize developmental outcome.
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