Three cell line mosaicism involving structural and numerical abnormalities of chromosome 18 in a 3.5-year-old girl: 47,XX,+18/47,XX,+del(18)(q22)/46,XX.

We report on a 3.5-year-old girl with a mosaic karyotype including full trisomy 18, normal cells and a majority of cells with partial trisomy involving an extra chromosome 18 deleted at band q22. She had cardiac and CNS anomalies, dysmorphic facial features failure to thrive and developmental delay. A gastrostomy tube was placed at 2 years of age. The combination of improved nutrition and optimal developmental therapy has led to her sitting supported, attempting to stand and enhancement of her cognitive and non-verbal communication abilities. Molecular investigation of the patient and her parents using microsatellite analysis has led to the conclusion that, as expected, the additional copy of chromosome 18 constituting the full trisomic cell line is maternal meiosis I in origin. The data, however, indicate that in the trisomic cell line containing the deleted chromosome 18q, the structurally abnormal 18 was of paternal origin. We think this case is the first described with both structural and numerical trisomic mosaicism involving chromosome 18 in a liveborn infant. We propose a mechanism of origin and review the literature, comparing the clinical presentation of this case with individuals having full or partial trisomy 18.

Ocular and systemic findings in the Aarskog (facial-digital-genital) syndrome.

The Aarskog (facial-digital-genital) syndrome is an X-linked disorder in which short stature is accompanied by hypertelorism, digital anomalies, and shawl scrotum. Except for hypertelorism and blepharoptosis, ophthalmic abnormalities have been rarely noted in this condition. We examined four patients who had Aarskog syndrome and unilaterally or bilaterally decreased vision on initial examination. Three family members had V-pattern esotropia, latent nystagmus, inferior oblique overaction, and amblyopia. A fourth patient had bilateral blepharoptosis and severe astigmatism. Other ocular features included hyperopia, anisometropia, deficient ocular elevation, blue sclerae, and posterior embryotoxon. These findings underscore the need for ophthalmic examination in asymptomatic patients with Aarskog syndrome to rule out treatable causes of visual loss.

Autism in association with fragile X syndrome in females: implications for diagnosis and treatment in children.

Fragile X syndrome is the second most common chromosomal cause of mental retardation (MR). The calculated incidence is 1/1000, making accurate and early diagnosis important for specific preventive, pharmacologic, and cognitive treatment. The timely diagnosis in males is facilitated by the characteristic phenotype and an association with autism. In contrast, in females heterozygous for fragile X, the characteristic phenotype and infantile autism are rarely reported. We present two females with cytogenetic expression of the fragile X chromosome for whom the studies were performed because of the presence of autism or prominent autistic features and a behavioral and physical phenotype consistent with fragile X syndrome. The first female, age three years, has autism, hyperactivity, echolalia, language delay, hand stereotypies, and mild MR. The characteristic phenotype was not present nor was there a family history of X-linked MR. Fragile X expression was 6% in the proband, 3% in the mother and 1% (normal) in the father. The second child, seven years old, has prominent autistic features, hyperactivity, mild MR, mild language disorder, and a family history consistent with X-linked MR. Fragile X expression was 3% in the proband and 0% in the mother. These cases support the occurrence of fragile X in autistic females and emphasize the importance of cytogenetic screening for fragile X in this high risk population. Early diagnosis of fragile X allows precise genetic counseling and more specific cognitive and pharmacologic treatment.