P 409. The Noonan’s Syndrome as a Differential Diagnosis of a Congenital Myasthenic Syndrome
30. Oktober 2018 (online)
Background: The Noonan’s syndrome is a multiple malformation syndrome which is characterized by a typical “Noonan facies” (hypertelorism, ptosis and large, low-set ears) short stature, minor mental retardation, cryptorchidism, and congenital heart disease. The estimated incidence is 1 in 1,000 births. In ∼50% of cases mutations in the PTPN11 gene were identified, a gene encoding the nonreceptor protein tyrosine phosphatase SHP-2. This leads to a change of the conformation of SHP-2 with the result of enzymatic overactivity (loss of inhibition) and/or to a deregulation of cell signaling pathways. The ubiquitous SHP-2 causes, through its participation in the signal transmission of growth and differentiation factors, differing effects in different tissues. This explains the variety of symptoms of the Noonan’s syndrome. Clinical findings show similarities to congenital myasthenic syndromes, in which affected patients may suffer from muscular weakness and a ptosis with temporal fluctuation.
Goal: First report of a successful symptomatic therapy with pyridostigmine bromide of a patient with genetically confirmed Noonan’s syndrome.
Purpose: As Noonan’s syndrome and CMS show a phenotypic overlap a differential diagnosis should be considered if patients show additional dysmorphic features or congenital malformations.
Methods: Summary of medical history and relevant clinical findings. Presentation of the results of neurography, blood tests, molecular genetic analysis, and motor testing.
Results: Postnatal feeding problems and muscular hypotonia were present. At the age of 5 years, the patient was introduced to a doctor with chewing problems as a sign of orofacial weakness and ptosis. In the clinical examination, a dysmorphic facies with large, low-set ears, and a generalized muscular hypotonia with a decrease in muscular strength in the course of the day were found. The repetitive stimulation of the n. accessorius of the right side detected a pathological decrement (13%). A multigene panel for CMS was negative. After starting a therapy with pyridostigmine bromide, the patient showed an increased muscular strength and decrease in ptosis, Besinger score before therapy 8 after therapy 4. In this case with dysmorphic features with ptosis and large, deep-set ears, a multigene panel testing was performed, which showed a mutation in the PTPN11 gene.
Conclusion: Noonan’s syndrome and CMS show phenotypic overlap. In the case of additional existing dysmorphism, a syndromic disease should be considered. In our case, therapy with pyridostigmine bromide improved muscle strength in the patient. It is currently unclear if (and to what extent) a disorder of nonreceptor protein tyrosine phosphatase with effects on the proliferation and differentiation of embryonic stem cells or a tissue-specific SHP-2 dysfunction leads to a disturbed formation of the neuromuscular end plate. This should be analyzed in further studies.