American Journal of Medical Genetics 44:635-637 (1992)
Brief Clinical Report Child With Multiple Congenital Anomalies and Mosaicism 46, XX/46,XX, del (14)(q32.3) Bruce Alan Miller, Parul Jayakar, and Hilda Capo Department of Ophthalmology, George Washington University Medical Center, Washington, D.C. (B.A.M.); Department of Pediatrics, Division of Genetics, Mailman Center for Child Development (P.J.) and Bascom Palmer Eye Institute, University of Miami School of Medicine (H.C.), Miami, Florida We report on a female infant with multiple congenital anomalies and severe developmental delay in association with a rare, terminal deletion of chromosome 14 [karyotype: mosaic. 46,XX/46,XX del (14) (q32.3) = 36%:64%1. 0 1992 Wiley-Liss,
KEY WORDS: human chromosome 14, chromosome deletion, chromosomal aberration, mosaic, multiple congenital anomalies
Inc.
Fig. 1. F’roposita aged
Received for publication December 20, 1991; revision received April 23, 1992. Address reprint requests to Bruce A. Miller, M.D., 3358 Second Street South, Arlington, VA 22204.
0 1992 Wiley-Liss, Inc.
2112
months.
636
Miller et al.
INTRODUCTION De novo deletions of 14q are rare. There have been only 8 previously reported cases of patients with 14q deletions not associated with ring formation, and only 3 had terminal deletions. None, to our knowledge, has expressed the particular mixoploid pattern present in our patient. CLINICAL REPORT R.E.W. (Fig. 1)was the 1,760 g female infant of a 38week pregnancy and was delivered in breech position by an uncomplicated cesarean section to a 26-year-old mother and a 26-year-old father. Pregnancy, delivery, and neonatal course were normal. There were no known exposuresto recognized teratogens. There was no family history of consanguinity, spontaneous abortions, congenital anomalies, or mental retardation. The father was adopted. Shortly after birth, multiple anomalies were recognized, including esophageal atresia with tracheoesophageal fistula, intestinal malrotation, coronal craniosynostosis unilateral left nuclear cataract, small orbits, downward slant of palpebral fissures, apparently lowset ears, small mouth and nose with a depressed nasal
bridge, . . maxillary hypoplasia, and mildly digitalized thumbs. The patient remained in the hospital for the first 4 months of life, undergoing multiple operations. At 6 months, she was below the fifth centile for length, weight, and head circumference, and she was delayed in psychomotor performance. Neurologically, a generalized hypotonia was present. An MRI of the brain was normal. A cochlear defect was found on brainstem auditory-evoked potentials. The child lived until age 2 years. The cause of death was respiratory failure.
CYTOGENETIC STUDIES Routine chromosome analysis performed shortly after birth on phytohemagglutinin (PHAI-stimulated peripheral lymphocytes documented a normal 46, XX chromosome complement. A repeat high resolution G-banded chromosome analysis done on PHA-stimulated lymphocytes disclosed two cell lines: normal 46, XX in 36% (15/42 cells examined) and an abnormal cell line, 46,XX, del (14Mq32.3) in 64% (27/42 cells examined), with a terminal deletion involving a portion of band q32.3 of 14q (Fig. 2). Parental chromosomes are normal. Satellite polymor-
9
22
n
Fig. 2. Idiogram showing the terminal deletion in chromosome 14 and its normal homologue.
Chromosome 14 Deletion phisms using G-banding did not uncover the origin of the deletion.
DISCUSSION Apparently, no cases of a terminal deletion of chromosome 14 with the above described mosaic pattern have been reported. Manifestations that the proposita had in common with other reported cases of 14q deletions include craniosynostosis, downward slant of palpebral fissures, apparently low-set ears, small mouth, small nose and depressed nasal bridge, thumb anomaly, hypotonia, and psychomotor retardation [Gorski et al., 1990; Hreidarsson et al., 1983; Nielson et al., 1978; Telford et al., 1990; Yen et al., 19881. Findings which seem to be unique in the proposita include esophageal atresia with tracheoesophageal fistula, intestinal malrotation, and unilateral cataract. In this case, the given diagnosis after the first (normal) chromosome study was acrocephalocraniostenosis, type undefined. The definitive high resolution chromosome study allowed the proper diagnosis. This highlights the need for utilization of currently available studies in the face of diagnostic difficulties. Many findings have been reported in chromosome 14
637
abnormalities, but the lack of consistent findings has made it impossible to define a specificclinical entity. We hope this case and others will help to better delineate chromosome 14 abnormalities.
ACKNOWLEDGMENTS We gratefully acknowledge the assistance of Neil F. Notaroberto, M.D. for his invaluable technical assistance. REFERENCES Gorski J L Uhlmann W, Glover T (1990): A child with multiple congenital anomalies and karyotype 46, XY, del (14) (q31q32.3): Further delineation of chromosome 14 deletion syndrome. Am J Med Genet 37:471-474.
Hreidarsson S, Stamberg J (1983): Distal monosomy 14 not associated with ring formation. J Med Genet 20:147-149. Nielson J , Homma A, Ramussen K, Ried E, Sorensen K, SaldanaGarcia P (1978): Deletion 14q and pericentric inversion 14. J Med Genet 15:236-238. Telford N, Thomson DA, Griffiths MJ, Ilett S,Watt J L (1990): Terminal deletion (14Xq32.3): A new case. J Med Genet 27:261-263. Yen F, Podruch P, Weisskopf B (1988):A terminal deletion(l4) (q31.1) in a child with microcephaly, narrow palate, gingival hypertrophy, protuberant ears, and mild mental retardation. J Med Genet 26:130-133.
Brief Clinical Report Child With Multiple Congenital Anomalies and Mosaicism 46, XX/46,XX, del (14)(q32.3) Bruce Alan Miller, Parul Jayakar, and Hilda Capo Department of Ophthalmology, George Washington University Medical Center, Washington, D.C. (B.A.M.); Department of Pediatrics, Division of Genetics, Mailman Center for Child Development (P.J.) and Bascom Palmer Eye Institute, University of Miami School of Medicine (H.C.), Miami, Florida We report on a female infant with multiple congenital anomalies and severe developmental delay in association with a rare, terminal deletion of chromosome 14 [karyotype: mosaic. 46,XX/46,XX del (14) (q32.3) = 36%:64%1. 0 1992 Wiley-Liss,
KEY WORDS: human chromosome 14, chromosome deletion, chromosomal aberration, mosaic, multiple congenital anomalies
Inc.
Fig. 1. F’roposita aged
Received for publication December 20, 1991; revision received April 23, 1992. Address reprint requests to Bruce A. Miller, M.D., 3358 Second Street South, Arlington, VA 22204.
0 1992 Wiley-Liss, Inc.
2112
months.
636
Miller et al.
INTRODUCTION De novo deletions of 14q are rare. There have been only 8 previously reported cases of patients with 14q deletions not associated with ring formation, and only 3 had terminal deletions. None, to our knowledge, has expressed the particular mixoploid pattern present in our patient. CLINICAL REPORT R.E.W. (Fig. 1)was the 1,760 g female infant of a 38week pregnancy and was delivered in breech position by an uncomplicated cesarean section to a 26-year-old mother and a 26-year-old father. Pregnancy, delivery, and neonatal course were normal. There were no known exposuresto recognized teratogens. There was no family history of consanguinity, spontaneous abortions, congenital anomalies, or mental retardation. The father was adopted. Shortly after birth, multiple anomalies were recognized, including esophageal atresia with tracheoesophageal fistula, intestinal malrotation, coronal craniosynostosis unilateral left nuclear cataract, small orbits, downward slant of palpebral fissures, apparently lowset ears, small mouth and nose with a depressed nasal
bridge, . . maxillary hypoplasia, and mildly digitalized thumbs. The patient remained in the hospital for the first 4 months of life, undergoing multiple operations. At 6 months, she was below the fifth centile for length, weight, and head circumference, and she was delayed in psychomotor performance. Neurologically, a generalized hypotonia was present. An MRI of the brain was normal. A cochlear defect was found on brainstem auditory-evoked potentials. The child lived until age 2 years. The cause of death was respiratory failure.
CYTOGENETIC STUDIES Routine chromosome analysis performed shortly after birth on phytohemagglutinin (PHAI-stimulated peripheral lymphocytes documented a normal 46, XX chromosome complement. A repeat high resolution G-banded chromosome analysis done on PHA-stimulated lymphocytes disclosed two cell lines: normal 46, XX in 36% (15/42 cells examined) and an abnormal cell line, 46,XX, del (14Mq32.3) in 64% (27/42 cells examined), with a terminal deletion involving a portion of band q32.3 of 14q (Fig. 2). Parental chromosomes are normal. Satellite polymor-
9
22
n
Fig. 2. Idiogram showing the terminal deletion in chromosome 14 and its normal homologue.
Chromosome 14 Deletion phisms using G-banding did not uncover the origin of the deletion.
DISCUSSION Apparently, no cases of a terminal deletion of chromosome 14 with the above described mosaic pattern have been reported. Manifestations that the proposita had in common with other reported cases of 14q deletions include craniosynostosis, downward slant of palpebral fissures, apparently low-set ears, small mouth, small nose and depressed nasal bridge, thumb anomaly, hypotonia, and psychomotor retardation [Gorski et al., 1990; Hreidarsson et al., 1983; Nielson et al., 1978; Telford et al., 1990; Yen et al., 19881. Findings which seem to be unique in the proposita include esophageal atresia with tracheoesophageal fistula, intestinal malrotation, and unilateral cataract. In this case, the given diagnosis after the first (normal) chromosome study was acrocephalocraniostenosis, type undefined. The definitive high resolution chromosome study allowed the proper diagnosis. This highlights the need for utilization of currently available studies in the face of diagnostic difficulties. Many findings have been reported in chromosome 14
637
abnormalities, but the lack of consistent findings has made it impossible to define a specificclinical entity. We hope this case and others will help to better delineate chromosome 14 abnormalities.
ACKNOWLEDGMENTS We gratefully acknowledge the assistance of Neil F. Notaroberto, M.D. for his invaluable technical assistance. REFERENCES Gorski J L Uhlmann W, Glover T (1990): A child with multiple congenital anomalies and karyotype 46, XY, del (14) (q31q32.3): Further delineation of chromosome 14 deletion syndrome. Am J Med Genet 37:471-474.
Hreidarsson S, Stamberg J (1983): Distal monosomy 14 not associated with ring formation. J Med Genet 20:147-149. Nielson J , Homma A, Ramussen K, Ried E, Sorensen K, SaldanaGarcia P (1978): Deletion 14q and pericentric inversion 14. J Med Genet 15:236-238. Telford N, Thomson DA, Griffiths MJ, Ilett S,Watt J L (1990): Terminal deletion (14Xq32.3): A new case. J Med Genet 27:261-263. Yen F, Podruch P, Weisskopf B (1988):A terminal deletion(l4) (q31.1) in a child with microcephaly, narrow palate, gingival hypertrophy, protuberant ears, and mild mental retardation. J Med Genet 26:130-133.
