Ophthalmologic observations in a patient with partial mosaic trisomy 8.

BACKGROUND: To carefully assess the phenotype and genotype of a patient with partial mosaic trisomy 8 with particular attention to ophthalmologic features. METHODS: Ophthalmologic and neuro-ophthalmologic examination; neuroimaging; conventional karyotyping; and array comparative genomic hybridization (CGH). RESULTS: The proband was the only affected child of a non-consanguineous family. At birth she was noted to have facial dysmorphism including telecanthus, low set ears, prominent nares, and an everted lower lip. She had an accommodative esotropia with otherwise normal globes, optic nerves, retinae, and orbits. She also had delayed motor milestones and mild mental retardation associated with agenesis of the corpus callosum. Both karyotyping and array CGH documented mosaic partial trisomy of chromosome 8 that included all of the "q" arm and part of the proximal "p" arm. CONCLUSIONS: This girl had a number of the classic features of mosaic trisomy 8, including an accommodative esotropia with none of the other ocular and orbital anomalies described in patients with mosaic trisomy 8. This report constitutes an initial effort to create a virtual database of patients with mosaic chromosome 8 in which careful phenotype-genotype correlation employing high resolution array CGH may help identify clues regarding the genetic etiology of ophthalmologic features of this syndrome.

3M syndrome: an easily recognizable yet underdiagnosed cause of proportionate short stature.

OBJECTIVE: To characterize, via clinical and molecul criteria, a cohort of patients with 3M syndrome and thereby increase awareness of this syndrome as a recognizable cause of proportionate short stature. STUDY DESIGN: We conducted a case series of patients referred to clinical genetics for proportionate short stature. CUL7, OBSL1, and CCDC8 genes were clinically phenotyped and sequenced. RESULTS: In 6 Saudi families with 3M syndrome, we identified three CUL7, one OBSL1, and one CCDC8 novel mutations, which we show result in a remarkably similar clinical phenotype. Despite their typical and easily discernible clinical phenotype, all these patients have been extensively investigated for alternative causes of their short stature and received erroneous diagnoses. CONCLUSION: Increased awareness about this syndrome among pediatricians and endocrinologists is needed to avoid a costly and unnecessary diagnostic odyssey.