Cardiofaciocutaneous syndrome (CFC) with congenital peripheral neuropathy and nonorganic malnutrition: An autopsy study

Abstract

Many phenotypic manifestations have been reported in cardiofaciocutaneous (CFC) syndrome, but none, to date, are pathognomonic or obligatory. Previous histopathological studies reported findings in skin and hair; no autopsy studies have been published. We report the clinical and autopsy findings of a 7‐year‐old boy with severe CFC syndrome and malnutrition of psychosocial origin. Manifestations of CFC, reported previously, included macrocephaly and macrosomia at birth; short stature; hypotonia; global developmental delays; dry, sparse thin curly hair; sparse eyebrows and eyelashes; dilated cerebral ventricles; high cranial vault; bitemporal constriction; supraorbital ridge hypoplasia; hypertelorism; ptosis; exophthalmos; depressed nasal bridge; anteverted nostrils; low‐set, posteriorly‐rotated, large, thick ears; decayed, dysplastic teeth; strabismus; hyperelastic skin; wrinkled palms; keratosis pilaris atrophicans faciei; ulerythema ophryogenes; hyperkeratosis; gastroesophageal reflux; and tracheobronchomalacia. Additional findings, not previously reported, include islet cell hyperplasia, lymphoid depletion, thymic atrophy and congenital hypertrophy of peripheral nerves with onion bulb formations. Although the islet cell hyperplasia, lymphoid depletion, and thymic atrophy are nonspecific findings that may be associated with either CFC or malnutrition, the onion bulb hypertrophy is specific for a demyelinating–remyelinating neuropathy. These findings implicate congenital peripheral neuropathy in the pathogenesis of the developmental delays, feeding difficulties, respiratory difficulties, ptosis and short stature in this case. Additional studies of other cases of CFC are needed. © 2005 Wiley‐Liss, Inc.

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. 42 Abnormalities include ventriculomegaly, hydrocephalus, cortical atrophy, prominent Virchow-Robin spaces, and abnormal myelination.…”

“…[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.…”

“…Gastroenterologists can differentiate the constipation caused by intestinal dysmotility from other less common conditions such as intestinal malrotation, functional megacolon, anal stenosis, or rarely intestinal atrophy. 41,44,57 Constipation can continue into adulthood and follow-up by a gastroenterologist may be helpful in planning a satisfactory bowel regimen.…”

Neurological complications of cardio‐facio‐cutaneous syndrome

“…9 There are several case reports where these neurological features are described in patients with CFC; however, there has never been a systematic evaluation of neurological involvement in this condition. [10][11][12][13][14][15] This report describes neurological features of the largest cohort of mutation-positive individuals with CFC reported to date.…”

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

“…In a large series of CFC syndrome patients, the percentage of children who have undergone a brain CT or MRI ranges from 38% to 50% [Gross-Tsur et al, 1990;Wieczorek et al, 1997;Manci et al, 2005]. The incidence of structural brain abnormalities in CFC patients who have undergone brain imaging ranges from 9.4-85.7% [Gross-Tsur et al, 1990;Wieczorek et al, 1997;Manci et al, 2005].…”