DOI: https://doi.org/10.36347/sjmcr.2026.v14i09.030

Pages: 2088-2091

Cardio-facio-cutaneous (CFC) syndrome is an exceptionally rare RASopathy, with fewer than 300 cases reported worldwide, caused predominantly by de novo pathogenic variants in BRAF. We report the first molecularly confirmed Moroccan case, a 4-year-9-month-old girl born to non-consanguineous parents, presenting with severe global developmental delay (absent autonomous walking, marked speech delay, intellectual disability), severe growth retardation (height 86 cm), cutaneous xerosis, and subclinical hypothyroidism (TSH 7.58 µIU/mL with normal free T4). Brain and pituitary MRI, echocardiography, EEG, and karyotype were normal. Clinical exome sequencing identified a heterozygous pathogenic missense variant in BRAF (NM_004333.6: c.770A>G; p. Gln257Arg), classified as pathogenic in ClinVar (rs180177035), confirming the diagnosis of CFC syndrome. The variant was presumed de novo given the absence of parental consanguinity and the sporadic presentation; parental Sanger sequencing was recommended for formal confirmation. This case illustrates the phenotypic variability of CFC syndrome, showing that absence of structural cardiac malformation does not exclude the diagnosis when the molecular signature is present. The concurrent subclinical hypothyroidism represents an underrecognized endocrine complication warranting systematic thyroid screening in all affected patients. This report is the first molecularly confirmed case of CFC syndrome from Morocco, contributing to the geographic expansion of the known phenotypic spectrum of BRAF-related RASopathies.