label: applied to treat

initial_unit_of_measurement: milligram per kilogram (mg/kg)

initial_frequency: Daily / Once per day (QD)

current_unit_of_measurement: milligram per kilogram (mg/kg)

current_frequency: Daily / Once per day (QD)

unit_of_measurement_duration: Month(s)

treatment_on_going: Unknown

additional_drug_info: Patient was intubated during treatment due to respiratory distress. Because of multifocal atrial tachycardia with rapid ventricular response, propranolol (1 mg/kg t.i.d.) was introduced and serial 24 h ECG Holter monitoring was indicated. For the persistence of subentrant episodes of MAT, flecainide (5 mg/kg b.i.d.) and then intravenous amiodarone (5 mcg/kg minute) were added on top of beta-blocker therapy. Because the patient showed a persistent need for mechanical ventilation and severe bilateral involvement was detected on chest HRCT, treatment with dexamethasone was started, with partial recovery of respiratory parameters. Trametinib was added at week 9 to this background regimen because of sub-entrant, drug-resistant episodes of MAT and progressive decline in respiratory function. This case report was extracted from an article in the published literature. The article's reference information is: Lioncino M, Fusco A, Monda E, Colonna D, Sibilio M, Caiazza M, Magri D, Borrelli AC, D'Onofrio B, Mazzella ML, Colantuono R, Arienzo MR, Sarubbi B, Russo MG, Chello G, Limongelli G. Severe Lymphatic Disorder and Multifocal Atrial Tachycardia Treated with Trametinib in a Patient with Noonan Syndrome and SOS1 Mutation. Genes (Basel). 2022 Aug 23;13(9):1503. doi: 10.3390/genes13091503. PMID: 36140671; PMCID: PMC9498305.The free full text of the article is available at: https://pmc.ncbi.nlm.nih.gov/articles/PMC9498305/

sex: Male

age_group: < 1 month

country_treated: Italy

current_dose_change: No

unit_of_measurement_duration: Day(s)

treatment_on_going: No

additional_drug_info: At day +46 after treatment initiation, a ventriculoperitoneal shunt was placed in order to manage the intraventricular hemorrhage and a red blood cell unit was transfused. After surgery, we observed rapid worsening of CHF (nt-pro-BNP increased from 2049 pg/mL to 47,000 pg/mL) as well as respiratory deterioration, requiring again mechanical ventilator support. Pulmonary artery dilation, stable until then, increased to 18 mm (+5.7 SDS) and death from untreatable CHF with hypoxic respiratory failure occurred on day +57.This case report was extracted from a published article. The reference information for this article is: Mussa A, Carli D, Giorgio E, Villar AM, Cardaropoli S, Carbonara C, Campagnoli MF, Galletto P, Palumbo M, Olivieri S, Isella C, Andelfinger G, Tartaglia M, Botta G, Brusco A, Medico E, Ferrero GB. MEK Inhibition in a Newborn with RAF1-Associated Noonan Syndrome Ameliorates Hypertrophic Cardiomyopathy but Is Insufficient to Revert Pulmonary Vascular Disease. Genes (Basel). 2021 Dec 21;13(1):6. doi: 10.3390/genes13010006. PMID: 35052347; PMCID: PMC8774485.The free full text of the article is available at: https://pmc.ncbi.nlm.nih.gov/articles/PMC8774485/

sex: Female

treatment_on_going: Yes

additional_drug_info: This case report was extracted from a published article. The reference information for the article is: Leegaard A, Gregersen PA, Nielsen TØ, Bjerre JV, Handrup MM. Succesful MEK-inhibition of severe hypertrophic cardiomyopathy in RIT1-related Noonan Syndrome. Eur J Med Genet. 2022 Nov;65(11):104630. doi: 10.1016/j.ejmg.2022.104630. Epub 2022 Sep 30. PMID: 36184070.The free full-text of the article is available at: https://www.sciencedirect.com/science/article/pii/S1769721222002117?via%3Dihub

age_group: 4 - 6 months

country_treated: Denmark

additional_drug_info: At day of life 3, she developed frequent atrial ectopy with rapid atrial rate and numerous P wave morphologies. Echocardiogram was performed and demonstrated early hypertrophic cardiomyopathy with concentric left ventricular hypertrophy, pulmonary valve stenosis, and atrial septal defect. Based on the cardiac manifestations, macrocephaly, and widely spaced nipples, a RASopathy sequencing panel was performed, revealing a RAF1 c.770C>T pathogenic variant. She was started onpropranolol and discharged on home oxygen at 4 weeks. At 6 weeks, she presented with respiratory failure because of coronavirus HKU1 requiring intubation. Her arrhythmias and hypertrophic cardiomyopathy progressed, and she was diagnosed with MAT. The MAT frequently degenerated to atrial flutter/fibrillation with rapid ventricular response requiring multiple cardioversions. Progressive escalation of antiarrhythmic therapies included esmolol infusion, nadolol, amiodarone, and flecainide without successful rhythm or rate control. She developed chylothoraces requiring pleural tubes with inability to extubate because of congestive heart failure and severe left mainstem bronchomalacia. At 17 weeks, she had 2 cardiac arrests caused by degeneration of her MAT in the setting of high antiarrhythmic doses, resulting in polymorphic ventricular tachycardia requiring defibrillation. Her flecainide was transitioned to diltiazem infusion while continuing on amiodarone and nadolol. Because of her recalcitrant MAT and progressive biventricular hypertrophy, management options were discussed including cardiac transplantation, and the decision was made to pursue compassionate use of pharmacological MEK inhibition.While on trametinib, she developed severe diarrhea for which her trametinib was held for 3 days and dose was reduced to 0.01875 mg/kg per day, during which atrial ectopy briefly returned. Amiodarone and diltiazem were slowly weaned and discontinued. She remained on trametinib and nadolol with trivial residual atrial ectopy <1% of beats. This case was reported in the published literature. The article reference information is: Meisner JK, Bradley DJ, Russell MW. Molecular Management of Multifocal Atrial Tachycardia in Noonan's Syndrome With MEK1/2 Inhibitor Trametinib. Circ Genom Precis Med. 2021;14(5):e003327. doi:10.1161/CIRCGEN.121.003327. PMID: 34463117. The free full text link to the article is: https://www.ahajournals.org/doi/10.1161/CIRCGEN.121.003327?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed

ethnicity: Unknown

country_treated: United States


name: SYNGAP1-related developmental and epileptic encephalopathy

initial_unit_of_measurement: milligram (mg)

initial_frequency: 2 times a day (BID)

initial_route: Oral (PO)

current_unit_of_measurement: milligram (mg)

current_frequency: 2 times a day (BID)

current_route: Oral (PO)

current_dose_change: Yes

treatment_begin_month: June

additional_drug_info: increased dose 3 times. now we are giving her 500 mg. We also give it all in one dose in the morning as her school would not administer it. Although it works great all in the morning.

age_group: 1 - 5 years

ethnicity: Not Hispanic/Latino

race:
Black or African American
White

initial_unit_of_measurement: grams (g)

current_unit_of_measurement: grams (g)

unit_of_measurement_duration: Year(s)

additional_drug_info: Symptoms come back as soon as we stop. We also see less benefits when taking generic brand of Tanganil.

age_group: 6 - 10 years


initial_unit_of_measurement: milliliters (mL)

current_unit_of_measurement: milliliters (mL)


initial_unit_of_measurement: Other

initial_route: Topical

current_unit_of_measurement: Other

current_route: Topical

additional_drug_info: Clobetasol propionate 0.05% topical; Keratosis pillaris and hyperkeratosis were described as "Dermatologic condition including rough, dry areas on the skin of his arms and legs gradually developed into blisters with surrounding erythema and subsequent scaling, multiple cup-shaped hyperkeratotic, inflammatory papules with significant scale on his scalp, face, trunk, and upper and lower limbs, all the lesions had a ‘‘nutmeg grater’’ texture"


additional_drug_info: The hypertrophic cardiomyopathy had decreased by 7 days after ACTH treatment was discontinued. Left ventricular stroke volume decreased from 10.5 to 5.9 mL.

country_treated: Japan


country_treated: Canada


initial_frequency: Every 14 Days / Every Two Weeks

initial_route: Subcutaneous (Sub-Q)

current_frequency: Every 14 Days / Every Two Weeks

current_route: Subcutaneous (Sub-Q)

additional_drug_info: We noticed a failure of all topical (steroids, calcineurin inhibitors, and vitamin D3 analogues) or systemic medications (acitretin up to 0.5 mg/kg, methotrexate 20 mg/week, subcutaneous injections of ustekinumab 45 mg every 12 weeks).Despite dupilumab therapy being capable of inducing drastic reductions of IgE synthesis in patients with atopic dermatitis (13), the reduction of IgE concentrations at 18 months of treatment is moderate in this case of CFC. This is in contrast with the observed strong and durable improvement of skin symptoms.This case report was extracted from the published literature. The reference information for the publication is: Altandi SA, Apoil PA, Mazereeuw-Hautier J, Severino-Freire M. Cardio-facio-cutaneous Syndrome with Severe Inflammatory Cutaneous Lesions: Dramatic Effect of Dupilumab. Acta Derm Venereol. 2024 Sep 5;104:adv40465. doi: 10.2340/actadv.v104.40465. PMID: 39235050; PMCID: PMC11388110.The free full text of the article is available at: https://pmc.ncbi.nlm.nih.gov/articles/PMC11388110/

age_group: 21 - 30 years

country_treated: France


additional_drug_info: Diarrhea with each increase dose.


name: Noonan syndrome with multiple lentigines

treatment_begin_month: February

treatment_end_month: April

severity:
Outpatient
Inpatient
ICU/Critical Care

additional_drug_info: Patient born with severe hypertrophic cardiomyopathy with obstruction. Patient had open heart surgery (myectomy) at two months old 12/2019.  Everolimus started in February 2020. Continued medication with titrations until April 2022. No significant changes in hypertrophic cardiomyopathy. Decided to discontinue Everolimus to see impact on patient’s condition. Patient currently 4 yrs old and hypertrophic cardiomyopathy consider considered mild to moderate. No scientific evidence Everolimus contributed to HCM stabilization, but hopeful!


additional_drug_info: Hydrocortisone 2.5% topical; Keratosis pillaris and hyperkeratosis were described as "Dermatologic condition including rough, dry areas on the skin of his arms and legs gradually developed into blisters with surrounding erythema and subsequent scaling, multiple cup-shaped hyperkeratotic, inflammatory papules with significant scale on his scalp, face, trunk, and upper and lower limbs, all the lesions had a ‘‘nutmeg grater’’ texture"


initial_unit_of_measurement: micrograms (mcg) (µg)

initial_frequency: Every Month /Monthly / Every Four Weeks

initial_route: Intramuscular (IM)

current_unit_of_measurement: micrograms (mcg) (µg)

current_frequency: Every Month /Monthly / Every Four Weeks

current_route: Intramuscular (IM)

severity: Outpatient Inpatient


additional_drug_info: Used in combination with midazolam, phenobarbital and valproic acid to try to control refractory seizures.


additional_drug_info: Used in combination with levetiracetam, phenobarbital and valproic acid to try to control refractory seizures.


additional_drug_info: Mometasone furoate 0.1% topical; Keratosis pillaris and hyperkeratosis were described as "Dermatologic condition including rough, dry areas on the skin of his arms and legs gradually developed into blisters with surrounding erythema and subsequent scaling, multiple cup-shaped hyperkeratotic, inflammatory papules with significant scale on his scalp, face, trunk, and upper and lower limbs, all the lesions had a ‘‘nutmeg grater’’ texture"


additional_drug_info: Used in combination with midazolam, levetiracetam, and valproic acid


additional_drug_info: Pimecrolimus 1% topical treatment; Keratosis pillaris and hyperkeratosis were described as: "Dermatologic condition including rough, dry areas on the skin of his arms and legs gradually developed into blisters with surrounding erythema and subsequent scaling, multiple cup-shaped hyperkeratotic, inflammatory papules with significant scale on his scalp, face, trunk, and upper and lower limbs, all the lesions had a ‘‘nutmeg grater’’ texture"


treatment_begin_month: October


unit_of_measurement_duration: Week(s)


additional_drug_info: Tacrolimus 0.1% topical; Although persistent, the lesions showed marked improvement with heat avoidance, including the lack of development of new skin lesions. This case was unique in that it reported previously unreported histopathologic findings in CFC of eccrine squamous metaplasia and periadnexal granuloma. Keratosis pillaris and hyperkeratosis were described in the article as "Dermatologic condition including rough, dry areas on the skin of his arms and legs gradually developed into blisters with surrounding erythema and subsequent scaling, multiple cup-shaped hyperkeratotic, inflammatory papules with significant scale on his scalp, face, trunk, and upper and lower limbs, all the lesions had a ‘‘nutmeg grater’’ texture."This case report was extracted from a published article. The article's reference information is: Jeffries ML, Aleck KA, Bernert RA, Hansen RC. Eccrine squamous metaplasia and periadnexal granulomas: new cutaneous histopathologic findings in cardiofaciocutaneous syndrome. Pediatr Dermatol. 2010 May-Jun;27(3):274-8. doi: 10.1111/j.1525-1470.2009.00982.x. Epub 2009 Oct 4. PMID: 19804494.The full text of the article is available at: https://onlinelibrary.wiley.com/doi/10.1111/j.1525-1470.2009.00982.x


initial_route: Nasogastric (NG)

current_route: Gtube

treatment_begin_month: January

severity:
Outpatient
ICU/Critical Care

additional_drug_info: At dose of 0.025 mg/kg patient had clinically significant rhabdomyolysis with myoglobinuria. She had an elevated troponin which lead to temporary discontinuation of medication. While off trametinib patient continued to have intermittent elevated troponins, though to be due to her congenital heart disease and not trametinib. Did not have rhabdomyolysis at 0.0125 mg/kg dose. Checked patient's pharmacogenomics as well as trametinib level at the time of rhabdomyolysis which was normal.

age_group: 7 - 11 months

ethnicity: Hispanic/Latino


additional_drug_info: Triamcinolone 0.1% topical. Keratosis pillaris and hyperkeratosis were described in the article as "Dermatologic condition including rough, dry areas on the skin of his arms and legs gradually developed into blisters with surrounding erythema and subsequent scaling, multiple cup-shaped hyperkeratotic, inflammatory papules with significant scale on his scalp, face, trunk, and upper and lower limbs, all the lesions had a ‘‘nutmeg grater’’ texture". This case report was extracted from a published article. The article's reference information is: Jeffries ML, Aleck KA, Bernert RA, Hansen RC. Eccrine squamous metaplasia and periadnexal granulomas: new cutaneous histopathologic findings in cardiofaciocutaneous syndrome. Pediatr Dermatol. 2010 May-Jun;27(3):274-8. doi: 10.1111/j.1525-1470.2009.00982.x. Epub 2009 Oct 4. PMID: 19804494.The full text of the article is available at: https://onlinelibrary.wiley.com/doi/10.1111/j.1525-1470.2009.00982.x


additional_drug_info: Used in combination with midazolam, levetiracetam, and phenobarbital for control of refractory seizures.This case report was extracted from the published literature. The reference information for the case is: Lenet S, Polychronakos C. Endocrine abnormalities in cardiofaciocutaneous syndrome: a case of precocious puberty, hyperprolactinemia and diabetes insipidus. BMJ Case Rep. 2019 Jun 18;12(6):e229032. doi: 10.1136/bcr-2018-229032. PMID: 31217210; PMCID: PMC6586202.The full text of the article is available at: https://pmc.ncbi.nlm.nih.gov/articles/PMC6586202/


additional_drug_info: The patient was treated with antiepileptic drugs (levetiracetam, zonisamide, clonazepam, topiramate, phenobarbital, and lamotrigine), intravenous immunoglobulin, thyrotropin-releasing hormone, and a ketogenic diet but showed no decrease in clinical seizures or improvement in EEG findings. Finally, we decided to administer vigabatrin with the consent of our hospital’s ethics committee and written informed consent from theparents, because vigabatrin has not been approved for use in Japan.This case report was extracted from the published literature. The reference information for the published case is: Hatori T, Sugiyama Y, Yamashita S, Hirakubo Y, Nonaka K, Ichihashi K. Vigabatrin Therapy for Infantile Spasms in a Case of Cardiofaciocutaneous Syndrome with Cardiac Hypertrophy Developing during Adrenocorticotropic Hormone Treatment. J Nippon Med Sch. 2016;83(4):167-71. doi: 10.1272/jnms.83.167. PMID: 27680485.The free full text of the article is available at: https://www.jstage.jst.go.jp/article/jnms/83/4/83_167/_article