Clinical Guidance

Genotype-phenotype correlations are still emerging with a detailed analysis in adults . . Based on limited data, individuals with the highly recurrent c.1498AG (p.Ile500Val) pathogenic variant are more likely to have prenatal growth deficiency with postnatal short stature and severe aortic obstruction. . Individuals with the c.1486CT (p.Arg496Cys) pathogenic variant are more likely to have a height within the normal range for age and sex. Females with this pathogenic variant are more likely to have premature puberty and heavy menses . Of the six individuals reported with neoplasia, three were women with endometrial cancer, two of whom were heterozygous for the c.1486CT (p.Arg496Cys) pathogenic variant.

Source: GeneReviews — "Myhre Syndrome"

Diagnostic Criteria

No consensus clinical diagnostic criteria for Myhre syndrome have been published.

Suggestive Findings

Myhre syndrome should be suspected in individuals with the following clinical and imaging findings and family history. Although no single feature is pathognomonic, co-occurrence of some findings is highly suggestive of Myhre syndrome (see for frequency of select features).

Clinical findings

Source: GeneReviews — "Myhre Syndrome"

Differential Diagnosis

The disorders that most closely resemble Myhre syndrome are the other acromelic dysplasias – geleophysic dysplasia, acromicric dysplasia, and Weill-Marchesani syndrome – which share the findings of thickened skin, short stature, short hands, and stiff joints . lists these and other syndromes that have more limited overlapping features. Table 4. Disorders of Interest in the Differential Diagnosis of Myhre Syndrome

Management Guidelines

Although formal evidence-based clinical management guidelines for Myhre syndrome have not yet been published, expert consensus recommendations provide pragmatic clinical guidance (Table 5 in and Table 2 in ). Evaluations Following Initial Diagnosis To establish the extent of disease and needs in an individual diagnosed with Myhre syndrome, the evaluations summarized (if not completed previously as part of the diagnostic evaluation) are recommended. Table 5. Myhre Syndrome: Recommended Evaluations Following Initial Diagnosis

Source: GeneReviews — "Myhre Syndrome"

Clinical Guidance

Affected individuals should be aggressively counseled not to smoke. Limiting tissue trauma (injury) appears to be the single most important preventive concept in this disorder to communicate to all health care providers involved in an individual's care . Decision making with affected individuals and their families should include nonintervention as an option in, for example, ear piercing, orthodontic braces, exploratory procedures, or surgical repair of velopharyngeal insufficiency. Elective tracheal surgery/intubation should be avoided when possible. Tracheal resection is contraindicated. Growth hormone therapy is not currently recommended for affected individuals with short stature.

Source: GeneReviews — "Myhre Syndrome"

Therapies Under Investigation

The antihypertensive drug losartan is an angiotensin II type 1 receptor blocker. Through this mechanism, it also indirectly antagonizes transforming growth factor beta (TGF-) signaling. In Myhre syndrome fibroblasts, losartan corrected an extracellular matrix deposition defect . Thus, in a small uncontrolled open-label pilot study, three individuals with Myhre syndrome were treated with losartan. Improvements in skin thickness, joint range of motion, and myocardial strain were observed . However, long-term controlled clinical trials with a larger number of affected individuals are needed to establish the efficacy of losartan on skin, joint, and heart abnormalities in Myhre syndrome. Search ClinicalTrials.

Source: GeneReviews — "Myhre Syndrome"

Surveillance Guidelines

To monitor existing manifestations, the individual's response to supportive care, and the emergence of new manifestations, the evaluations summarized in are recommended. Table 7. Myhre Syndrome: Recommended Surveillance

Source: GeneReviews — "Myhre Syndrome"