A very short, microcephalic, and mentally retarded 2 year old girl showed minor anomalies including prominent occiput, delayed closure of the anterior fontanelle, high frontal hairline, prominent ears, upward slanting palpebral fissures, a small nose with bulbous tip, delayed tooth eruption and bone maturation, and short and tapering fingers and toes. She did not have a white forelock. Cytogenetic investigation disclosed a de novo unbalanced translocation between chromosomes 4 and 18 with deletion of 4q12-->q21.1. Molecular investigation showed lack of a paternal allele for the microsatellite markers D4S392 and D4S398. This case shows indirect evidence that the piebald gene maps to proximal 4q12.
Three patients and one fetus with almost complete trisomy 17p due to familial rearrangements are described. Two patients followed unbalanced transmission of a familial pericentric inversion, and one patient and one fetus were due to unbalanced segregation of familial translocations. In the inversion family, another two patients with multiple malformations had died before chromosome examination could be performed. The pattern of congenital anomalies as revealed from eleven cases of trisomy 17p11-pter include as the most prominent features: prenatal growth retardation, microcephaly, downslanting palpebral fissures, small mouth, small mandible, poorly shaped ears, short and webbed neck, genital hypoplasia, clinodactyly of fingers, crowding of toes, a high incidence of congenital heart defects and hernias. Postnatal survival is short mainly in patients with congenital heart defects. From the age of about 6 years onward, clinical findings become more distinct, with some signs of Charcot-Marie-Tooth neuropathy (pes cavus, adducted thumbs, dorsiflexed hallux, camptodactyly and limitation of movements in different joints), and the nose gets narrow and sharp, with hypoplastic alae.
A 7 year old girl with intrachromosomal triplication 46,XX,-15,+der(15)(pter-->q13::q13-->q11::q11-->qter) resulting in tetrasomy of 15q11-q13 is reported. Fluorescence in situ hybridisation confirmed that the tetrasomic region included the entire segment normally deleted in Prader-Willi and Angelman syndrome patients, and breakpoints were similar to those reported in two tandem duplications of 15q11-q13. The middle repeat was inverted, suggesting a possible origin through an inverted duplication intermediate. Microsatellite analysis showed that the rearrangement was of maternal origin and involved both maternal homologues. Clinical findings included multiple minor anomalies (a fistula over the glabella, epicanthic folds, downward slanting palpebral fissures, ptosis of the upper lids, strabismus, a broad and bulbous tip of the nose, and small hands and feet), motor and mental retardation, a seizure disorder, and limited verbal abilities. In addition, immunological examination disclosed a selective immunodeficiency. The overall phenotype did not clearly resemble that of cases with tetrasomy 15pter-q13 associated with an extra inv dup(15)(pter-->q13:q13-->pter) chromosome. The latter aberration causes more severe mental deficit and intractable seizures, but less marked phenotypic alterations, although some overlap in mild facial dysmorphic features is present. A number of features common to Angelman syndrome were also observed in the patient.
