Joubert syndrome (JS) is an autosomal recessive disorder characterized by cerebellar vermis hypoplasia, hypotonia, developmental delay, apnea/hypernea and ophthalmologic abnormalities. Since its description, most attention has focused on hindbrain malformations and the hallmark molar tooth sign (MTS) when visualized on axial magnetic resonance imaging (MRI). Few reports have described a characteristic clinical phenotype of JS and a large cohort of patients has not undergone dysmorphology examinations. In addition, very little is known about other conditions which share some of the clinical and radiological features of JS, including, Arima, Senior-Löken, Dekaban, COACH, and Varadi (OFD VI) syndromes. The purpose of this study was to document the morphologic characteristics of Joubert syndrome based upon detailed dysmorphology and anthropometric examinations in a large cohort of JS individuals to determine whether JS is associated with a specific pattern of malformation. Dysmorphology findings included long face, frontal prominence, bitemporal narrowing, ptosis, prominent nasal bridge and tip, prognathism, eyebrow abnormalities, trapezoid shaped mouth, lower lip eversion, and thick ear lobes. Anthropometric analyses showed several significant differences in measurements including bizygomatic, frontal, nasal, and mandibular dimensions. When compared to controls, younger JS patients had significantly increased facial widths whereas older patients had longer mandibular arc lengths. These data indicate that JS lacks a clear, specific recognizable pattern of malformation, despite being associated with several dysmorphic facial characteristics and distinct anthropometric facial patterns, which change with age. Variability and overlap of features in JS and other hindbrain syndromes makes clinical diagnosis difficult and probably reflects genetic heterogeneity within the cohort of patients with the MTS.

Tertiary trisomy, or double trisomy, is a rare occurrence. We present two individuals with a previously unreported tertiary trisomy for chromosomes 5p and 21q in an eight-generation pedigree. Their phenotypes are compared with other partial trisomies of either 5p or 21q from the literature. The propositus was diagnosed with trisomy 21 at 2 years of age after a karyotype study for short stature and developmental delay. His phenotype was described as atypical for Down syndrome. He presented at 9 years of age because of pervasive behavioral problems and obesity. He was brachycephalic with a flattened nasal bridge, but he lacked other characteristics of trisomy 21. Because of lack of phenotypic evidence of Down syndrome, a repeat karyotype was obtained and showed 47,XY, +der(21)t(5;21)(p15.1; q22.1), incorporating partial trisomies of both chromosomes 5 and 21. Mother had a balanced translocation, 46, XX,t(5;21)(p15.1; q22.1); 8 other relatives were examined. The translocation originated from the maternal great-grandmother, but only the propositus and his mentally retarded aunt had a similar phenotye and the derivative chromosome. Fluorescence in situ hybridization showed absence of band 21q22.2 in the derivative chromosome of the propositus and his aunt, indicating that neither had trisomy for the Down syndrome critical region. These cases represent a unique double partial trisomy of chromosome arms 5p and 21q that occurred because of 3:1 malsegregation of a reciprocal translocation. These cases further demonstrate that phenotypic discordance with cytogenetic results dictate further investigation using advanced cytogenetic hybridization.