Paula and Bobby
Parents of Lillie
Myhre syndrome (MYHRS)
What is Myhre syndrome (MYHRS)?
This rare disease is incredibly rare, with less than 100 recorded cases worldwide to dare.
Although it is believed many cases go undiagnosed and that the number of recognised cases continues to increase due to improved awareness and testing.
The main features of the syndrome include unique facial features, and intellectual disability.
Growth-mental Deficiency Syndrome Of Myhre Laryngotracheal Stenosis, Arthropathy, Prognathism, And Short Stature; Laps Syndrome Myhre syndrome
What gene changes cause Myhre syndrome (MYHRS)?
Mutations to the SMAD 4 gene are responsible for the syndrome. The condition may be inherited or occur as the result of a de novo mutation. Most of the cases reported are due to a sporadic 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.
When inherited it is inherited in an autosomal dominant pattern. 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.
What are the main symptoms of Myhre syndrome (MYHRS)?
Intellectual and behavioral problems are common to the syndrome and many individuals also receive a diagnosis of autism or are found to be on the autism spectrum disorder. Mild to moderate intellectual disability is a widely recognized symptom.
Unique facial features of the syndrome include small, narrow eye openings, a flat face, prominent nose, a prominent jaw that becomes more prominent with age.
Other physical symptoms include short stature, skeletal abnormalities, limited joint mobility, a build of scar tissue in the skin and internal organs, lung abnormalities and heart defects relating mainly to the aora, hearing problems, largely abnormal appearing muscles, a narrowing of the voice box.
Possible clinical traits/features:
Autosomal dominant inheritance, Platyspondyly, Precocious puberty, Seizure, Thin vermilion border, Short neck, Non-midline cleft lip, Obesity, Overlapping toe, Pericardial effusion, Patent ductus arteriosus, Respiratory failure, Radial deviation of finger, Camptodactyly, Thick eyebrow, Midface retrusion, Stiff skin, Clinodactyly, Ptosis, Vertebral fusion, Short long bone, Thickened calvaria, Sparse hair, Thin upper lip vermilion, Microcephaly, Strabismus, Short philtrum, Prominent nasal bridge, Hernia of the abdominal wall, Generalized muscle hypertrophy, Hypertension, Hypertelorism, Hypermetropia, Short finger, Cognitive impairment, Short stature, Hearing impairment, Hypoplastic iliac wing, Hypoplasia of the maxilla, Short toe, Fine hair, Brachydactyly, Displacement of the urethral meatus, Thickened skin, EMG abnormality, Limitation of joint mobility, Malar flattening, Cleft palate, Coarctation of aorta, Cone-shaped epiphysis, Craniofacial hyperostosis, Cryptorchidism, Deeply set eye, Behavioral abnormality,
How does someone get tested for Myhre syndrome (MYHRS)?
The initial testing for Myhre 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 Myhre syndrome (MYHRS)
Short stature, characteristic facial features, fibrosis, congenital heart defects, hearing loss, and intellectual disability are seen in this disorder. Heterozygous mutations in the SMAD4 gene cause Myhre syndrome.
Two unrelated males were described by Myhre et al., (1981) with intellectual disability, short stature, a muscular build, decreased joint mobility and mixed hearing loss.
There was a similar facial appearance in both patients, with maxillary hypoplasia, prognathism and a short philtrum (one patient had a repaired cleft lip and palate). Radiographs revealed a thickened calvarium, a prominent broad mandible, hypoplastic iliac wings, broad ribs, shortened tubular bones and ""large flattened non-beaked vertebrae."" One case was thought to have an ASD.
A further possibly affected male was described by Soljak et al., (1983). Both reports mentioned similarities to Moore-Federman syndrome, but individuals from the family in that case report were not intellectually disabled (note Burglen et al., 2003). A further case was reported by Whiteford et al., (2001).
Burglen et al., (2003) reported four further cases, one with normal development. The authors noted that progressive thickening of the skin seems to be a feature, as is hypertension and mixed hearing loss in older patients. The authors provide a good review and stress the similarities to Moore-Federman, acromicric dysplasia, geleophysic dysplasia and LAPS syndrome.
A female with normal intelligence was reported by Rulli et al., (2005) and another female by van Steensel et al., (2005). This latter female had in addition stiff skin, hypertrophic scar formation and fusion of vertebral bodies.
Three new patients were reported by McGowan et al., (2011). The facial appearance, thickened skin (in two in a mosaic pattern), and muscular habitus were ""memorable"" features. A progressive, proximal, tracheal stenosis developed in one, and another died following a choking episode. Note similarities with LAPS syndrome.
Titomanlio et al., (2001) reported a further case with autism. Skin biopsy showed a thick dermis with a close-packed woven network of collagen. The subcutaneous fat was arranged in lobules that were separated by unusually thick interlobular septa. There were also some inflammatory changes.
An additional female (Mexican) patient was reported by Becerra-Solano et al., (2008). These authors review the literature and comment that all female patients to date have a square body build. This was also present in the case reported by Brachmann-Gagescu et al., (2011). The patient also had cerebellar atrophy and was ataxic.
Occasionally, patients have cataracts and retinitis pigmentosa, and a maculopathy has also been described (Al Ageeli et al., 2012).
Caputo et al., (2012) mapped the condition using eight patients, and mutations were found in the tumor-suppressor gene SMAD4. Twenty-nine out of 32 cases had SMAD4 mutations (Michot et al., 2014). The three without had typical findings of Myhre syndrome.
Recurrent pericarditis has been reported (Picco et al., 2013). Garavelli et al., (2016) reported a patient who developed pericarditis, and they reviewed the evolution of the clinical features of Myhre syndrome in 48 patients. The authors concluded that pericarditis and laryngotracheal involvement constitute important life-threatening complications.
Alagia et al., (2017) described two years old female patient with Myhre syndrome due to a recurrent p.Ile500Val mutation in the SMAD4 gene. The patient had growth deficiency, slightly delayed development and dysmorphic features, including short palpebral fissures, hypertelorism, flat nasal bridge, highly arched palate, and brachydactyly. She also had tetralogy of Fallot and corectopia, which had not been previously reported.
* This information is courtesy of the L M D.
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