American Journal of Medical Genetics 37:318-319 (1990)

Brief Clinical Report

Cleft Lip and Palate in Aicardi Syndrome Elizabeth McPherson and Susan M. Jones Capitol Area Permanente Medical Group, Reston, Virginia (E.M.); Division of H u m a n Genetics, Department of Pediatrics, State University of New York, Buffalo, (S.M.J.)

Cleft lip and palate were described previously in two patients with Aicardi syndrome; this report presents a third similarly affected child. Thus, facial clefts may be an occasional manifestation of Aicardi syndrome. KEY WORDS: Aicardi syndrome, cleft lip, cleft palate INTRODUCTION Aicardi syndrome is characterized by agenesis of the corpus callosum, brain heterotopias, seizure disorder, chorioretinal lacunae, vertebral anomalies, and mental retardation [Aicardi et al., 1965; Bertoni et al., 1978; DeJong et al., 1976; Dennis and Bower, 1972; Hoyt et al., 1978; Levy et al., 1984; McMahon et al., 1984; Phillips et al., 1978; Renier et al., 1973; Willis and Rosman, 19801. The disorder is presumed to be caused by a n X-linked gene t h a t is lethal in the hemizygous male. Cleft lip and palate have been reported in two affected patients [Chevrie and Aicardi, 19861; we describe here a third patient with Aicardi syndrome and cleft lipipalate. CLINICAL REPORT The patient was born to a 25-year-old G2 P1 woman. The unrelated patents had a healthy daughter; the family history was negative for birth defects, mental retardation, and genetic disease. There was no history of exposure to known human teratogens. The pregnancy and labor were uneventful and the infant was born by spontaneous vaginal delivery. Unilateral cleft lip and cleft palate were noted; no other anomalies were appreciated. Early postnatal growth and development were reported to be normal. At age 6 weeks the infant was hospitalized for a seizure disorder. She had generalized seizures that remained uncontrolled despite treatment with phenobarbital, phenytoin, carbamazepine, and mysoline. Her electro-encephalogram was abnormal with right spike and sharp wave bursts. A trial of pyridoxine was withReceived for publication August 7,1989; revision received March 19, 1990. Address reprint requests to Susan M. Jones, M.S., Division of Human Genetics, Children’s Hospital, 219 Bryant Street, Buffalo, NY, 14222.

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out benefit. Ophthalmologic examination demonstrated lacunar defects initially interpreted as “colobomas”and “dysplastic” discs. CT scan of the brain showed agenesis of the corpus callosum with ventriculomegaly, irregularities of the ventricular wall, and a left occipital porencephalic cyst (Fig. 1).Renal ultrasonography showed no abnormality. Voiding cystourethrogram was normal. Radiographs showed no vertebral malformations. Brain auditory evoked response was normal with the exception of a mild first wave delay. Chromosomes were normal. The infant was discharged a t age 4 months despite uncontrolled seizures. The child was readmitted a t age 7 months. There had been essentially no psychomotor development and she had almost continual seizures. Length was 67.5 cm (50th centile); weight was 7.56 kg (50th centile); OFC was 42 cm (10th centile). She had significant gastroesophageal reflux. She was brachycephalic with mild right occipital and left frontal flattening. Inner canthal distance was 3.0 cm (>97th centile). The nasal bridge was low and broad. The left-sided unilateral cleft lip had been repaired; the left-sided cleft palate was unrepaired. The heart and lungs were normal to auscultation. Abdomen, genitalia, and limbs were unremarkable. The child was hypertonic and hyperreflexic. No skin lesions were noted. Repeat ophthalmologic examination showed chaotic gaze movements, lacunar defects, and colobomas of the optic nerves. Electroretinogram was normal and visual evoked response was slightly prolonged on the left. Repeat EEG revealed hypsarrhythmia and repeat CT scan showed no change from previous studies. Developmental assessment a t age 14 months showed developmental functioning below a 1-month level. The child was noted to have sensory awareness of high intensity auditory and visual stimuli with no evidence of cortical processing of these stimuli. At age 15 months a second ophthalmologist and a neuro-ophthalmologist examined the child. She failed to fix or follow with either eye and did not react to a bright light or to a menace reflex. She held her eyes in constant rightward gaze without nystagmus. The globes were of normal size. Fundus examination showed “punched-out” lesions in the right fundus with peripapillary hyperpigmentation. In the left eye there was irregular spotted pigmentation without lacunae. The maculae were not involved. The examiners thought the findings were typical of Aicardi syndrome.

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tion with Aicardi syndrome is too small to generate a statistically meaningful statement about clefting as a complication of this disorder. Nonetheless, these 3 cases suggest that cleft lip and/or palate may be a rare finding of Aicardi syndrome and that this disorder should be added to the list of syndromes (over 300) [Gorlin et al., 19901 known to be associated with facial clefting.

REFERENCES

Fig. 1. CT scan showing agenesis of the corpus callosum, mild ventriculomegaly with irregularities of the ventricular walls, and left occipital porencephalic cyst.

DISCUSSION Aicardi syndrome has been described in over 180 patients; we think that our case represents the third affected patient reported to have a cleft lip and palate. A particular malformation is presumed to be an occasional component of a syndrome if the malformation occurs more frequently in patients with the syndrome than in individuals in the general population. However, such assessments can be difficult to make if the total number of known patients with a particular syndrome is small and the individual malformation occurs in only a minority of patients with the underlying disorder. Many syndromes with midline defects show cleft lip or palate as a n occasional finding [Opitz and Gilbert, 19821; since Aicardi syndrome involves the midline (agenesis of corpus callosum), the occasional association of orofacial clefts should not be surprising. The sample size (3) of patients reported to have cleft lip and palate in associa-

Aicardi J, LeFebvre J, Lerique-Koechlin A (1965): Spasm in flexion, callosal agenesis, ocular abnormalities: A new syndrome. Electroencephalogr Clin Neurophysiol 19:609-610. Bertoni JM, von Loh S, Allen RJ (1978):The Aicardi syndrome: Report of four cases and review of the literature. Ann Neurol 5475-482. Chevrie JJ, Aicardi J (1986): The Aicardi syndrome. In Pedley TA, Meldrum BS (eds): “Recent Advances in Epilepsy.” Edinburgh: Churchill-Livingstone; pp 189-210. DeJong JGY, Delleman JW, Houben M, Manschot WA, De Minjer A, Mol J , Slooff J L (1976):Agenesis of the corpus callosum, infantile spasms, ocular anomalies (Aicardi’s syndrome). Neurology 26:1152- 1158. Dennis J , Bower BD (1972): The Aicardi syndrome. Dev Med Child Neurol 14:382-390. Gorlin R J , Cohen MM, Levin LS (1990): “Syndromes of the Head and Neck,” 3rd ed. New York: McGraw-Hill. Hoyt CS, Billson F, Ouvrier R, Wise G (1978): Ocular features of Aicardi’s syndrome. Arch Ophthalmol 96291-295. Levv Y. Waisman Y. Weitz R. Kiviti S. Nissenkorn I. Wiisenbeek J. Steinherz R (1984):Aicardlsyndrome: A cause of infantile seizures: Clin Pediatr (Phila) 23:284-287. McMahon RG, Bell RA, Moore GRW, Ludwin SK (1984): Aicardi’s syndrome: A clinicopathologic study. Arch Ophthalmol 102: 250-253. Opitz JM, Gilbert EF (1982): CNS anomalies and the midline as a “developmental field. Am J Med Genet 12:443-455. Phillips HE, Carter AP, Kennedy J L , Rosman NP, OConnor J F (1978): Aicardi’s syndrome: Radiologic manifestations. Radiology 127: 453-455. Renier W, Gabreels F, Mol L, Korten J (19731: Agenesis of the corpus callosum, chorioretinopathy and infantile spasms (Aicardi syndrome). Psychiatr Neurol Neurochir 76:39-45. Willis J, Rosman NP (1980):The Aicardi syndrome versus congenital infection: Diagnostic considerations. J Pediatr 96:235-239.

Cleft lip and palate in Aicardi syndrome.

Cleft lip and palate were described previously in two patients with Aicardi syndrome; this report presents a third similarly affected child. Thus, fac...
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