Paula et Bobby
Parents de Lillie
Qu'est-ce que Hemifacial Microsomia?
Hemifacial (one side of the face) Microsomia is a rare disease, the defining feature of which is the underdevelopment of one half of the face. This underdevelopment may be mild or severe. It is known to vary from individual to individual. However in every individual diagnosed, an undeveloped lower jaw is a consistent feature.
This syndrome is also known as:
Facio-auriculo-vertebral syndrome Facioauriculovertebral Sequence Facioauriculovertebral syndrome Fav Sequence Goldenhar Syndrome Hemifacial Microsomia Hemifacial Microsomia; HFM MYT1-related Oculo-auriculo-vertebral spectrum (OAVS) Oav Dysplasia OAVS Oculo-auriculo-vertebral syndrome Oculoauriculovertebral Dysplasia Oculoauriculovertebral Spectrum; Oavs Oculoauriculovertebral syndrome
Quelles sont les causes des changements génétiques Hemifacial Microsomia?
Il existe des preuves suggérant qu'il s'agit d'une maladie héréditaire, car des cas de syndrome ont été signalés au sein de la même famille. Cependant, le gène exact qui pourrait être responsable n'a pas encore été identifié.
La recherche actuelle suggère que le syndrome est causé par une perturbation du développement du ftus, au cours des 6 premières semaines de grossesse. On ne sait pas encore si les facteurs environnementaux peuvent également y contribuer.
Le mode exact d'héritage était inconnu au moment de l'enregistrement de cette entrée.
Quels sont les principaux symptômes de Hemifacial Microsomia?
Les principaux symptômes du syndrome affectent le visage. Les mâchoires inférieures et supérieures sous-développées sont la principale caractéristique. Ainsi qu'une bouche inclinée vers le haut. Ces caractéristiques peuvent à leur tour rendre la mastication difficile pour les individus.
Certaines personnes ont la joue et le front aplatis du côté sous-développé du visage, et une orbite oculaire peut également être plus petite. Une asymétrie faciale générale est fréquente, ce qui peut entraîner une perte de sensation dans la moitié affectée du visage et une faiblesse des muscles.
D'autres caractéristiques relatives au visage comprennent un excès de peau autour des oreilles, une oreille sous-développée et parfois absente, des structures de l'oreille interne absentes ou sous-développées et par conséquent une perte auditive également.
Le syndrome est un trouble du spectre, ce qui signifie que chaque partie du visage touchée peut varier dans sa gravité. Les symptômes peuvent également varier au sein des familles touchées par le syndrome.
Comment quelqu'un se fait-il tester pour Hemifacial Microsomia?
The initial testing for Hemifacial Microsomia (Goldernhar 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
Informations médicales sur Hemifacial Microsomia
This condition affects the face bilaterally, but asymmetrically. The ear is small, often with preauricular ear tags in a line between the front of the ear and the side of the mouth, and there is macrostomia and failure of formation of the mandibular ramus and condyle. Various Tessier clefts (30, 4, 7, 9) - Vendramini-Pittoli et al., 2015). An epibulbar dermoid is usually insisted on as a diagnostic feature. Where this is absent, and both sides of the face are affected, the term first and second branchial arch syndrome is perhaps preferable. Where the face is affected only on one side without an epibulbar dermoid then the term Hemifacial Microsomia has been used. Okajima et., (1996) studied 592 patients with microtia and found that males were affected more often (65%) and the right side was more often more affected (58.4%). Six patients were thought to have Treacher Collins syndrome and 27 patients were thought to have a first and second branchial arch syndrome.
Colobomas of the eyelid (including the upper lid - Seah et al., 2002) do occur. A case with optic nerve hypoplasia and an optic nerve coloboma was reported by Menon et al., (2004), and one with trigeminal nerve hypoplasia and corneal hypoesthesia by Villanueva et al., (2005). The patient reported by Chaudhuri et al., (2007) had a morning glory disc anomaly, with bilateral choroidal colobomas. Unilateral sclerocornea and trachial stenosis was reported by Furtado et al., (2011). Shimizu et al., (2004) reported an unusual case with a supernumerary auricle on the lateral canthus, and D'Alessandro et al., (2006) had a case with a horseshoe lung. A patient with polyotia and a bifid tongue was reported by Konas et al., (2006). Unilateral craniosynostosis was reported by Terry and Ascherman, 2006). A patient with a fibroepithelial polyp arising from the epibulbar dermoid was described by Seymenoglu et al., (2013). This was an usual case in that there was thumb polydactyly.
The case reported by Ghi et al., (2008) is difficult to place. There were preauricular tags, an epibulbar dermoid and a coloboma of the upper lid and early ossification of one coronal suture. But what makes this case unusual was the presence of a huge orbital cyst that replaced the eye.
Cervical vertebral anomalies are common and should be looked for. Cardiac defects have been reported in 5-58% of cases - Kumar et al., (1993) review the types of lesion. Two-thirds of anomalies are either tetralogy of Fallot or VSD, however Kumar et al., (1993) found a wide variety of lesions including a double outlet right ventricle, pulmonary atresia, and infradiaphragmatic total anomalous pulmonary venous drainage. Rad (2014) reported a case with right circumflex aortic arch, severe coarctation and a vascular ring. Maat-Kievit et al., (1994) reported a case with total situs inversus. Reid and Huff (1990) reported a similar association where the child had some additional features of VATER association. Lin et al., (1998) review cases of oculoauriculovertebral syndrome associated with abnormalities of situs. They note the association with maternal diabetes, as do Ewart-Toland et al., (2000). Zelante et al., (1997) reported another case with features of VATER association and a complex congenital heart defect. Bergmann et al., (2003) discuss the overlap between VACTERL association, Hemifacial Microsomia and axial mesodermal dysplasia. Thumb hypoplasia might be a feature (Das et al., 2008, Guzelmansur et al., 2013).
Ozkinay et al., (2003) reported a 10-year-old girl with a sliding type oesophageal hernia and ectopic pancreatic tissue in the stomach with renal agenesis and features of Hemifacial Microsomia. Pridjian et al., (1995) reported a case with mosaic trisomy 22 who had features of Goldenhar syndrome. A further case of Hemifacial Microsomia associated with partial duplication 22q was reported by Hathout et al., (1998). De Ravel et al., (2001) reported one case with features of the condition who had mosaic trisomy 9 and a further case with mosaic trisomy 22. Choong et al., (2003) reported a case with features of Goldenhar syndrome and Cri du Chat syndrome with a terminal 5p14 deletion. Josifova et al., (2004) reported a sib pair with an unbalanced t(5;8)(p15.31;p23.1) translocation. 5p14-5 seems interesting! Dabir and Morrison (2005) reported a case with trisomy 10p.
Severe central nervous system involvement is rare but hydrocephalus, microcephalus, encephalocele and severe retardation have been described. This association is well reviewed by Schrander-Stumpel et al., (1992) who point out that intracranial lesions are more frequently associated with cleft lip/palate, and anophthalmia or microphthalmia. A case with unilateral anophthalmia, microtia and severe obstructive hydrocephalus was reported by Kumar et al., (2009). Inci and Saglam (1995) reported a case with syringohydromyelia. Michaud and Sheridan (1974) reported a similar case. Cohen et al., (1995) carried out detailed psychological assessments on 24 children. 58% of children scored 2 SD below the mean in at least one domain of development.
Vento et al., (1991) introduced the OMENS classification standing for orbit, mandible, ear, cranial nerves and soft tissues. In each of these categories the abnormalities are graded from 0 (normal) to 3 (most severe). Horgan et al., (1995) used this system to analyse the defects in 121 patients and found that patients with extracraniofacial structural defects had higher OMENS grades.
Van Bever et al., (1992) reported eight Brazilian cases with rarer manifestations of the condition including Rokitansky sequence, dextrocardia, fibrous dysplasia of the bones, hydrocephalus and porencephalic cysts (see above), radial defects and hemimelia. Pillay et al., (2005) also reported a case with the Rokitansky sequence, a Dandy-Walker malformation and an absent thymus. This seems like something else. Maymon et al., (2001) reported a 20 week old fetus with right pulmonary agenesis associated with right microtia. These rarer features can lead to overlap with CHARGE, MURCS and VATER associations (Van Meter and Weaver, 1996). Sutphen et al., (1995) reviewed 60 cases and found that three had tracheo-oesophageal fistula or oesophageal atresia. Inglis et al., (1992) and Lin et al., (1995) reported cases with vertically fused tracheal cartilages. Ghose et al., (1992) reported a case with Peters' anomaly. Three cases with a portal vein cavernoma, presenting with extrahepatic portal hypertension, are known (Stringer et al., 2005).
Inheritance is uncertain - irregular dominant families have been described (Herrmann and Opitz, 1969; Robinow et al., 1986; Regenbogen et al., 1982; Rollnick et al., 1983; Stoll et al., 1998). Some of these families include convincing cases of Goldenhar syndrome (Singer et al., 1994, Tasse et al., 2007). On the other hand several discordant monozygotic twins have also been described (Boles et al., 1987; Burck et al., 1983; Connor and Fernandez, 1984; Ebbesen et al., 1982; Kawira et al., 1984; Setzer et al., 1981). Ferraris et al., (1999) reported a baby with features of Goldenhar syndrome in one of triplets derived from in vitro fertilisation. A similar case in one of triplets was reported by Roesch et al., (2001). Harris et al., (1996) studied the epidemiology of anotia and microtia and found a prevalence of between 0.76 and 2.35 per 10,000. Between 30-50% had associated malformations and approximately 15% of these cases had Goldenhar syndrome. Affected monozygotic twins (with slightly different manifestations) were reported by Touliatou et al., (2006), and sibs with Hemifacial Microsomia by Park and Tatum (2007). Nine familial cases were reported by Vendramini-Pittoli and Kokitsu-Nakata (2009). It should be noted that epibulbar dermoids did not occur, and that relatives were less severely affected.
Mastroiacovo et al., (1995) review the epidemiology and genetics of microtia. In the Italian population the prevalence was about 1.5 per 10000 with 22% of cases having anotia and 66% having an isolated ear defect. A significant association with maternal diabetes was noted.
Kelberman et al., (2001) mapped the gene to 14q32 in a large dominant family with a form of Hemifacial Microsomia, however the gene did not map to this position in another family, indicating genetic heterogeneity. Descartes (2006) reported a patient with Goldenhar syndrome and a 5p15.33-pter deletion, and summarized five other patients with Goldenhar syndrome / Hemifacial Microsomia and a 5pter deletion. Kosaki et al., (2007) reported a family in which one member had the Towns-Brooks phenotype, whereas her sister had features of Goldenhar including an epibulbar dermoid. Both had SALL1 mutations.
Note the case reported by Su et al., (2007) with (I think) hemi-facial microsmia (there were no eye abnormalities) with a TCOF1 mutation - there was facial asymmetry, hypoplasia of the left mandibular ramus and mandible, both conductive and sensorineural hearing loss, atresia of the auditory canal and multiple pinnae. Three patients with features compatable with Goldenhar, were found to have 22q11.2 microdeletions (Digilio et al., 2009) and another by Lafay-Cousin et al., (2009) and Xu et al., (2008). see also Balci and Engiz (2011).
Lopez et al. (2016) identified heterozygous mutations in the MYT1 gene in two patients with OAVS. The first patient carried a de novo nonsense mutation. She presented with preauricular and jugal tags, small and dysplastic pinnae on the right side and right epibulbar dermoid, facial asymmetry, vertebral malformations and conductive deafness. Temporal bones CT scan revealed a stenosis of the external auditory canal and an ossicular malformation affecting the incus and the malleus. She also had a ventricular septal defect and epilepsy. At age six, the patient showed normal neurological and growth development. In another patient, the missense mutation was inherited from his father. This boy presented with Hemifacial Microsomia, macrostomia, preauricular tag and dysplastic pinnae and a sacrococcygeal dimple. He had lipoma of filum and low attached spinal cord. His father presented with a progressive bilateral sensorineural hearing loss, myopia and a thoracolumbar scoliosis.
Berenguer et al. (2017) described a family with Hemifacial Microsomia due to heterozygous mutations in the MYT1 gene. Clinical characteristics included unilateral microtia, preauricular tag, ear dysplasia, conductive hearing loss, facial asymmetry, mandibular, malar, and maxillary hypoplasia, vertebral anomalies and septal defects.
A female patient with Hemifacial Microsomia was treated by Cassi et. al. (2017) and treated with an asymmetrical functional activator (AFA) to stimulate the growth of the affected side and consequently to improve symmetry.
A female patient with Oculo-auriculo-vertebral Spectrum (OAVS) was found to have a 1048 kb deletion in the 22q11.2 region by Spineli-Silva et. al. (2017). Clinical characteristics included cleft lip and palate, jejunal stenosis and bilateral hydronephrosis, atrial and ventricular septal defects, flat occiput, low-set ears, bilateral preauricular tags, stenosis of left auditory canal, malar hypoplasia, epicanthus, mild asymmetry of the face, right nasal cleft, and clinodactyly of the 5th finger.
Renkema et. al. (2017) performed a systematic review of vertebral anomalies in Hemifacial Microsomia spectrum. Anomalies included butterfly vertebrae, hemivertebrae, block vertebrae, scoliosis/kyphoscoliosis, spina bifida occulta, occipitalization of the atlas, hypoplastic atlas, platybasia, instability C1–C2, split vertebrae, basilar invagination, accessory vertebrae, rotary subluxation, displaced vertebrae, hypoplastic odontoid, scoliosis/kyphoscoliosis, sacralization, cervical ribs, rib fusion, rib aplasia, rib hypoplasia, and extra ribs.
Brotto et. al. (2017) described imaging characteristics of 35 patients with OAFS. Findings included Internal carotid artery hypoplasia/agenesis and abnormal course, brain abnormalities, internal acoustic canal stenosis/aplasia, cochlear vestibular malformations, facial nerve bony canal anomalies, and oval window atresia.
A review of clinical and cytogenomic characteristics of 72 patients with OAVS was made by Bragagnolo et. al. (2017). Up to date, there is no agreement in the literature for the minimum phenotypic inclusion criteria, but the primary phenotype involves Hemifacial Microsomia with facial asymmetry and microtia. Most cases are sporadic and the aetiology of this syndrome is not well known. Clinical characteristics were microtia (100%), mandible/mandibular hypoplasia (94%), vertebral/rib anomalies (83%), conductive hearing loss (67%), ocular/orbital dystopia (56%), preauricular tags (44%), soft tissue macrostomia (43%), sensorineural hearing loss (42%), cardiac anomalies (39%), central nervous system involvement (22%), cleft lip and/or palate (19%), epibulbar dermoid (15%), genitourinary malformations (14%), coloboma of the upper eyelid (7%), and preauricular sinus (3%). Fifteen CNVs (copy number variations) were found in 13 out of 72 patients without a single candidate genomic region. Recurrent chromosomal imbalances were observed in chromosomes 4 and 22.
Bogusiak et. al. (2017) review is focused on Goldenhar clinical characteristics and management.
* This information is courtesy of the L M D.
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