Multidisciplinary Team In Neurofibromatosis Type 1.

Multidisciplinary team work in early detection of Neurofibromatosis type 1 syndrome (NF1S). NF1S is a clinically heterogeneous, neurocutaneous genetic disorder characterized by café-au-lait spots, iris Lisch nodules, axillary and inguinal freckling, and multiple neurofibromas. Penetrance is 100% until 20 years old, thus a proband with NF1 pathogenic variant may  be  considerably more or less severe in affected sibilings: a mild form proband may have severe form descendents and viceversa.

Available ERN-EYE Genturis (European Reference Network) for all patients with one of the rare genetic tumour risk syndromes of improving access to diagnosis, treatment and the provision of high-quality healthcare for patients with Rare Diseases.

 

We present a 8 years 5 months old male patient. He is the second born child in a young, non-related, healthy coulpe. Pregnancy, birth and postnatal development uneventfull. Negative family history for congenital malformations,genetic diseases, with no similar cases for another gene anomaly.

Due to uneven growth of inferior limbs, left limb lympheodema, some cafe-au-lait spots by the age of 2 years 7 months, he was reffered to a ortopaedic surgeon, and was diagnosed with plexiform neurofibroma.

 

Due to clinical features, the following management is recommended: neurolgical: attention deficit and mild intellectual dissability, dislalic language; cardiac, abdominal and pelvine USG- normal; genetic: cranio-facial dismorphia, ephelides, low inserted large ears, micrognatism; microdentia, short neck, thorax assymentry, abnormal dermatoglyphics, II-III partial cutaneos sindactily feet, multiple cafe au lait spots, inguinal and axilar freckles. Molecular testing: MLPA (P081): heterozygous microdeletion NF1 gene (17q11.2). Ocular: ortophoria, hypertelorism, bilateral epicantus, corrected hyperopia, 3 Lish nodules in right eye, 5 in left eye, normal fundus both eyes.

Clinical diagnosis is based on National Institute of Health criteria (NIH).

Differential diagnosis in NF1S: Legius syndrome; McCune-Albright syndrome, Noonan syndrome with lentigines; LEOPARD Syndrome; Proteus syndrome; Piebald, infantile myofibromatosis, schwannomatosis, multiple orbital neurofibromas.

According to NIH: the diagnosis is based on 4 out of 7 criterias and molecular confirmation.

NF1S is autosomal dominant inherited (50%) NF1 gene (17q11.2) or have a de novo NF1 pathogenic variant. Germline mosaicism in a parent with no clinical signs of NF1S is possible but much less likely.

Specific multisystem manifestations may occur.

Controlled trials of several therapeutic approaches to malignant peripheral nerve sheath tumors are available to individuals with NF1 [Karajannis & Ferner 2015].

For NF1S are recommended:

• Annual physical examination by a physician familiar with the disease;
• Annual ophthalmologic examination in early childhood; in older children and adults;
• Regular developmental assessment by screening questionnaire (in childhood);
• Regular blood pressure monitoring;
• Other studies (e.g., MRI) only as indicated on the basis of clinically apparent signs or symptoms;
• Monitoring of those who have abnormalities of the central nervous system, skeletal system, or cardiovascular system by an appropriate specialists;
• Genetic counseling.

As treatment in Romania : solumetinib is available: 25 mg/m² orally twice a day on an empty stomach until disease progression or unacceptable toxicity.