CNS imaging is a key diagnostic tool in the evaluation of patients with CFC syndrome: Two cases and literature review

Abstract

Cardio-facio-cutaneous (CFC) syndrome is characterized by a variable degree of cognitive impairment, and multiple congenital anomalies including characteristic facies, cardiac, and ectodermal abnormalities. CFC syndrome is caused by mutations in the genes BRAF, MEK1, or MEK2. Here we provide a follow-up report on two patients presenting distinct facial appearance and other features of the syndrome, and we present the first molecular evidence of paternal origin for a CFC-causing germline mutation. Brain imaging revealed a lipoma of the corpus callosum and periventricular leukoencephalopathy as well as a hypoplastic corpus callosum, and defects in myelinization, in each patient, respectively. A review of the literature showed that, although non-specific, ventriculomegaly, hydrocephalus, and cortical atrophy represent the most frequent imaging findings of brain anomalies in CFC syndrome. CNS abnormalities are significant diagnostic features of CFC syndrome and a brain MRI is recommended in individuals diagnosed with CFC or suspected of having CFC syndrome.

Cardio-Facio-Cutaneous Syndrome: Clinical Features, Diagnosis, and Management Guidelines

“…29,41,42 Peripheral neuropathy has been rarely documented in CFC, but may be underdiagnosed. 43,44 Brain MRI studies reveal structural malformations in 9% to 85% of patients with CFC.…”

“…43,44 Brain MRI studies reveal structural malformations in 9% to 85% of patients with CFC. 42 Abnormalities include ventriculomegaly, hydrocephalus, cortical atrophy, prominent Virchow-Robin spaces, and abnormal myelination. 40,42 Other structural anomalies such as type I Chiari malformation, arachnoid cyst, gray matter heterotopia, corpus callosum abnormalities, cerebellar calcification, and periventricular leukoencephalopathy have been reported.…”

“…42 Abnormalities include ventriculomegaly, hydrocephalus, cortical atrophy, prominent Virchow-Robin spaces, and abnormal myelination. 40,42 Other structural anomalies such as type I Chiari malformation, arachnoid cyst, gray matter heterotopia, corpus callosum abnormalities, cerebellar calcification, and periventricular leukoencephalopathy have been reported. [40][41][42] It has been suggested that central nervous system malformations are underreported in CFC because only 38% to 50% of children have had brain MRI or computed tomography scans.…”

“…40,42 Other structural anomalies such as type I Chiari malformation, arachnoid cyst, gray matter heterotopia, corpus callosum abnormalities, cerebellar calcification, and periventricular leukoencephalopathy have been reported. [40][41][42] It has been suggested that central nervous system malformations are underreported in CFC because only 38% to 50% of children have had brain MRI or computed tomography scans. 42,44 The fact that many children with CFC do have structural brain malformations suggests the need for brain imaging in patients with CFC, as finding morphologic brain changes could lead to better understanding of the individual' s neurologic findings or underlying diagnosis.…”

“…[40][41][42] It has been suggested that central nervous system malformations are underreported in CFC because only 38% to 50% of children have had brain MRI or computed tomography scans. 42,44 The fact that many children with CFC do have structural brain malformations suggests the need for brain imaging in patients with CFC, as finding morphologic brain changes could lead to better understanding of the individual' s neurologic findings or underlying diagnosis. For example, individuals with NS have relatively few central nervous system malformations, and a brain MRI with some of the above structural abnormalities may suggest a diagnosis of CFC rather than NS.…”