Frank Yen

Changing phenotype in Floating-Harbor syndrome

We report on a girl with Floating-Harbor syndrome, trigonocephaly due to metopic suture synostosis, preauricular pit, hypoplastic thumb, subluxated radial head, and Sprengel deformity. A review suggests that trigonocephaly may be an important craniofacial manifestation in this syndrome that is recognizable in infancy. With time, this finding appears to become less noticeable, and the face develops a triangular shape, accentuated by a broad and bulbous nose.

Case of partial duplication 2q3 with characteristic phenotype: Rare occurrence of an unbalanced offspring resulting from a parental pericentric inversion

We report on a male infant with partial trisomy 2q (q34-->qter) resulting from a maternal pericentric inversion of chromosome 2 (p25. 2q34). The infant had clinical findings similar to the characteristic phenotype associated with a partial duplication of chromosome 2q3. Carriers of pericentric inversions of chromosome 2 have an increased risk of pregnancy loss but have only rarely been reported to have a liveborn offspring with an unbalanced chromosome constitution. This case further confirms the risks associated with a pericentric inversion of chromosome 2 and is the second report with manifestations of the trisomy 2q3 phenotype.

Greig cephalopolysyndactyly syndrome : altered phenotype of a microdeletion syndrome due to the presence of a cytogenetic abnormality

A male had several features of Greig cephalopolysyndactyly syndrome (GCPS) and significant developmental delay. He was found to have a de novo chromosomal deletion of chromosome no. 7 involving p13; this resulted in loss of the zinc finger gene, GLI3, which is the candidate gene in this syndrome. Modification of the CGPS phenotype in a sporadic case emphasizes the importance of searching for a chromosomal origin of this autosomal dominant disorder. Detection of a chromosomal deletion in these patients may be associated with a poor prognosis from the standpoint of cognitive development, and the potential for other structural abnormalities not normally associated with GCPS.

Case of partial trisomy 9p and partial trisomy 14q resulting from a maternal translocation: Overlapping manifestations of characteristic phenotypes

We report on a female infant with partial trisomy 9p (pter-->p13) and partial trisomy 14q (pter-->q22) resulting from a 3:1 segregation of a maternal reciprocal translocation (9;14)(p13;q22). Both trisomy 9p and partial trisomy 14q have been described as recognized phenotypes with characteristic patterns of anomalies. This patient appears to be the first reported with a partial duplication of both 9p and 14q resulting in an overlapping phenotype including minor facial anomalies, cleft palate, and hand-foot anomalies. However, the facial findings were more pronounced than commonly observed in cases with only one or the other duplicated chromosome regions, resulting in a distinctive appearance.

Patient with terminal duplication 3q and terminal deletion 5q: Comparison with the 3q duplication syndrome and distal 5q deletion syndrome

Partial duplication of chromosome 3q is a well‐described condition of multiple congenital anomalies and developmental delay that resembles the Brachmann‐de Lange syndrome. Similarly, an emerging phenotype of a distal 5q deletion syndrome has recently been described. The combination of both chromosome abnormalities has not been previously described. We report on a child with both a de novo duplication of distal 3q (q27 → qter) and terminal deletion of 5q (q35.2 → qter). The patient had facial anomalies, hypoplastic toenails, lymphedema of the dorsum of the feet, type I Chiari malformation, a seizure disorder, and moderate developmental delays. The phenotype is compared and contrasted to the few reports of patients with similar terminal 3q duplications and 5q deletions. Our patient did not have the characteristic phenotype of the 3q duplication syndrome, suggesting that the chromosome region responsible for this phenotype is more proximal than the terminal 3q27 region. In addition, comparison with three other reported cases of terminal 5q35 deletions suggests a possible association of terminal 5q deletions with central nervous system (CNS) structural abnormalities.

XY gonadal dysgenesis associated with a multiple pterygium syndrome phenotype

Most phenotypic females with an XY male karyotype do not have significant extragenital anomalies; however, some patients with additional abnormalities have been described. We report on an individual with XY gonadal dysgenesis, mental retardation, microcephaly, growth retardation, and multiple pterygia. Although not previously reported, the possible relationship between these findings is discussed in the context of evident heterogeneity of XY gonadal dysgenesis.

Juvenile juxtacortical chondromyxoid fibroma of bone: a case report

Conventional intramedullary chondromyxoid fibroma (CMF) is a rare benign tumor of bone; juxtacortical lesions are rarer still, and juxtacortical lesions occurring in children are heretofore essentially unreported. We present a case of such a lesion in a 12-year-old boy. This patient, who was previously healthy, presented with a 1-week history of poorly defined pain and mild swelling in the region of the left proximal tibia. Magnetic resonance imaging and bone scan showed changes most consistent with an aggressive biological process. However, the permanent histologic sections showed a (pseudo) lobular pattern of spindle cells with minimal pleomorphism and other features consistent with CMF. A clonal abnormality was detected in 15% of tumor cells karyotyped, characterized by a break in the long arm of chromosome 6 and a balanced Robertsonian translocation involving chromosomes 14 and 21. The patient has remained well and free of recurrence for more than 4 years. In general, CMF needs to be distinguished from its mimicker low-grade chondrosarcoma, and it must be recognized as occurring on bone surfaces among a wide age range of individuals. Juxtacortical CMF has not proven to be unusually aggressive in adults nor in this child, and marginal (en-block) resection remains the treatment of choice.

Mild intellectual deficits in a child with 49,XXXXY

Severe mental retardation usually is present in males with a 49,XXXXY karyotype, although occasionally, intellectual functioning has been reported to be in the mild range of mental retardation. One child was previously described to have normal development at 15 months, but had mental retardation at 41 months. We present a male with 49,XXXXY who had mild-cognitive and motor delays and age-appropriate adaptive skills at 59 months. Greatest deficits were in expressive verbalizations similar to other male sex chromosome abnormalities. Mosaicism could not be demonstrated in blood or skin specimens. Although most males with 49,XXXXY syndrome will have significant mental retardation, findings in our patient and other reports suggest that variability in intellectual functioning may occur, in some instances, and may justify guarded optimism in affected males demonstrating close to or age-appropriate developmental skills through early childhood.

X chromatin and chromosome examination in aged women

X chromatin frequencies were compared between aged, middle-aged and young women and statistically significant decrease in frequency was found in the aged as compared to the middle-aged and the young women. For a subsample of aged women results of chromosome examinations were also available which allowed comparison of the frequencies of X chromatin and monosomy C; no significant correlation emerged. This latter finding indicates that karyotypic analysis is necessary for the determination of monosomy C; and that X chromatin counts from buccal mucosal cells cannot be substituted for the examination of karyotypes.

Chromosomal Mosaicism for Translocation Breakpoints in a Patient with Congenital Absence of the Uterus and Vagina

Background Congenital absence of the uterus and vagina (CAUV) is a well known syndrome in which a phenotypic females lack mullerian derived structures. Identification of the genes responsible for this disorder has been hampered because in general patients with CAUV cannot reproduce, and inheritance patterns of mutations cannot be traced. De novo translocation break points have been used successfully to aid in identifying genes responsible for a wide variety disorders and does not rely on a reproductive history for identifying the genes. Methods Chromosomal studies utilizing high-resolution banding were performed on peripheral leukocytes and fibroblast cultures from various sites on a patient with CAUV. Results We have identified tissue specific mosaicism in a patient with CAUV and de novo balanced translocations from leukocyte and tissue fibroblast cultures by GTG banding techniques. Chromosome analysis from leukocyte on the patients parents showed normal karyotypes while the patient herself had a more complex pattern. Studies on leukocyte cultures from this patient identified a 46, XX, t(8;13) q22.1;q32.1) de novo balanced reciprocal translocation. Analysis of metaphase spreads from fibroblasts cultures of the buttock region revealed a second set of chromosome mosaicism. One cell line was similar to the leukocyte culture with a 46, XX, t(8:13)(q22.1;q32.1) karyotype. The other cell line had three balanced translocations showing a 46, XX, t(1;12)(q23;q24.3), t(6;6)(q15;p25), t(8;13)(q22;q32) karyotype. These two cell lines were in a ratio of 20: 5 respectively. Chromosome analysis of fibroblast cultures from the breast region shows cells with both the simple and more complex translocation. Conclusion These results indicate the importance of analyzing multiple tissue samples in the process of locating de novo break points for gene identification. It also suggests that somatic mosaicism may be a mechanism in the pathogenesis of uterovaginal agenisis. Identification of the genes at the specific break points of these translocations is in progress.