The cardiofaciocutaneous syndrome was first described by Reynolds and co-workers in 1986. x Patients have a characteristic facial appearance, mental retardation, abnormal skin and hair, and congenital heart disease. Typical facial characteristics consist of a high forehead with bitemporal narrowing, downslanting of the palpebral fissures, a depressed nasal bridge, and posteriorly rotated ears with prominent helices. Poor vision, ptosis, strabismus, nystagmus, and optic atrophy have been noted in some of the cases reported to date.2 No specific etiology for the poor vision, nystagmus, or strabismus in this syndrome has been established, although optic atrophy and central nervous system dysfunction may be contributory factors.
A 9-year-old white boy was born at term to a 34-year-old mother and a 41-year-old father. Pregnancy was complicated by mild polyhydramnios. Birth weight was 3 kg (40th percentile), length 39.5 cm (50th percentile), and head circumference 34.9 cm (75th percentile). Dysmorphic features were noted at birth and included downslanting palpebral fissures; bilateral undescended testicles; and low-set, posteriorly rotated ears. During the newborn period, a cardiac evaluation revealed a patent foramen ovale and asymmetric septal hypertrophy, and renal ultrasound showed duplication of the calyceal system with an obstructed left ureter. Cutaneous abnormalities included hyperkeratosis. He had transient stridor resulting from a tubular epiglottis and mild laryngomalacia. A karyotype study was performed and was found to be normal.
During childhood, he had a partial nephrectomy. Skin biopsy showed hyperkeratosis and verrucous acanthosis. He had a bilateral heel cord lengthening for toe walking. Because of self-injurious behavior, he was admitted to the hospital at 8 V2 years of age for behavioral evaluation and assessment. Weight and head circumference were at the 50th percentile. Height was less than the third percentile. He had curly hair, a maculopapular rash, and a dermatofibroma of the left thigh. On cognitive assessment, he was functioning in the range of profound mental retardation. On genetic evaluation, he was diagnosed with the cardiofaciocutaneous (CFC) syndrome,1 although selfinjurious behavior had not been previously reported in this condition.
FIGURE: Nine-year-old boy with the cardiofaciocutaneous syndrome. Note bilateral ptosis and absence of eyebrows and lashes.
Because of long-standing poor vision noted by the parents since early childhood, an ophthalmological examination was requested. By history, he had been very sensitive to light since age 2 years and could not keep his eyes open outdoors. On examination, there was no nystagmus or strabismus. Visual acuity could not be fully assessed because of his cognitive function. However, he could fixate steadily on a small toy with either eye. He had total loss of eyebrows, partial loss of eyelashes, and bilateral ptosis (Figure). The fundus appeared normal except for a tilted optic disc OD. Retinoscopy showed - 5.00 = +0.50 x 120 OD and -5.00= +1.50 x 75 OS.
Because of the perceived poor vision and the photophobia, an electroretinogram was obtained showing markedly reduced cone responses (amplitude 16 to 20 microvolts; normal >100 microvolts) and low normal rod responses (amplitude 240 microvolts; normal >300 microvolts).
We propose that in some patients with the CFC syndrome, a cone or possibly cone-rod dystrophy may be responsible for the decreased vision and possibly for the nystagmus and strabismus sometimes seen in this condition. Unfortunately, we could not perform color vision testing on our patient because of his cognitive development. It is unclear whether his cone dystrophy is progressive or whether it is congenital and similar to achromatopsia. If it is congenital and is due to the same abnormal gene causing the CFC syndrome, we postulate that the genetic defect resulted in photoreceptor maldevelopment of the cones leading to a clinical picture similar to achromatopsia.
Pentao and co-workers described a girl with isodisomy of chromosome 14, multiple congenital malformations, and achromatopsia.3 It is possible that the gene for the CFC syndrome is on chromosome 14 and affects the development of the retina, as well as other organs, giving rise to the clinical phenotype seen in our patient. We recommend that patients with the CFC syndrome undergo electroretinographic studies and color vision testing looking for a cone dystrophy.
1. Reynolds JF, Neri G, Hermann JP, et al. New multiple congenital anomalies/retardation syndrome with cardio-facio-cutaneous involvement-the CFC syndrome. Am J Med Genet. 1986;25:413-427.
2. Grose-Tsur V, Gross-Kieselstein E, Amir N. Cardio-facio-cutaneous syndrome: neurological manifestations. Clin Genet. 1990;38:382-386.
3. Pentao L, Lewis RA, Ledbetter DH, et al. Maternal uniparental isodisomy of chromosome 14: association with autosomal recessive rod monochromacy. Am J Hum Genet. 1992;50:690-699.