American Journal of Medical Genetics 41:15-17 (1991)
Brief Clinical Report Interstitial Deletion of Chromosome 18[del(l8)(ql1.2q12.2or q12.2q21.11 Linda C. Surh, David H. Ledbetter, and Frank Greenberg Institute for Molecular Genetics (L.C.S.,D.H.L., F.G.) and Department of Biochemistry (L.C.S.),Baylor College of Medicine, Houston, Texas A 27-month-oldboy with mild developmental delay, growth delay, strabismus, midface hypoplasia, relative telecanthus, downslanting palpebral fissures, epicanthal folds, dental hypoplasia, and cardiac defects was found to have an interstitial deletion of chromosome 18 involving band q12.1 or q12.3.
KEY
WORDS: chromosome abnormality, chromosome 18
INTRODUCTION We report on a 27-month-oldwhite boy with an interstitial deletion of chromosome 18 involving band q12.1 or q12.3. Although he was previously suspected to have Williams syndrome, further clinical history and detailed physical examination were not consistent with that syndrome. CLINICAL REPORT The propositus (Fig. 1)was born at 38 weeks by dates to a gravida 2, para 1,23-year-old mother and 26-yearold father. The pregnancy was uncomplicated except for oral erythromycin treatment for a respiratory infection at 4 to 5 months’ gestation. He was delivered vaginally with Apgar scores of 3 at one minute, 5 a t 5 min with initial bagging. Oxygen was required for the first 30 hr. He appeared to be at 36 weeks of gestation by examination, with a birth weight of 2,780 g. He went home at 5 days. Breast feeding went well until age 6 months when he was switched to a lactose formula. He then began having multiple ear infections, documented episodes of pneumonia, diarrhea, and reduced weight gain. At age 9 months, lactose intolerance was diagnosed as the cause of his diarrhea. With appropriate diet management, he has had normal bowel movements without constipation. Received for publication March 5, 1990; revision received September 24, 1990. Address reprint requests to Frank Greenberg, M.D., Institute for Molecular Genetics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030.
0 1991 Wiley-Liss, Inc.
Psychomotor development was initially normal with smile at 3 weeks, sitting at 5 months, crawling at 9 months, and drinking from a cup a t 12 months. However, he walked a t 16 months and is not toilet trained at 27 months. He can make simple 3-word sentences and understands simple commands. At 22 months, he had a strabismus repair and wears glasses for hypermetropia. Behaviorly, he had a short attention span and was hyperdistractible. Family history was unremarkable. He was diagnosed as Williams syndrome elsewhere. The mother’s obstetrician referred him at the time of her second pregnancy t o confirm the diagnosis and provide recurrence risk counseling. Chromosome analysis was not previously done. Physical examination at 27 months showed a small, easily distractible male with a head circumference of 48.5 cm, height of 84.2 cm, and weight of 10.8 kg (all parameters 50% for 15 to 20 months). He had frontal bossing with mid-face hypoplasia, relative telecanthus, downslanting palpebral fissures with epicanthal folds. His nasal bridge was flat with a small nose, thin lips, and a normal appearing philtrum. Ears were normal in configuration and position. The palate appeared normal but there was dental hypoplasia of the upper central and lateral incisors with otherwise normal teeth. A grade l16 systolic ejection murmur was present at the right upper sternum. He had Tanner stage 1 male genitalia with bilaterally descended testes. Neurologically, he had intact cranial nerves II-XII, normal muscle tone and strength, and his reflexes were diminished (1+ ) but symmetric. Sensation and cerebellar functions were normal. Although hypoplastic nails were present on fingers and toes, his apparently normal sister also displayed this characteristic and upon further questioning, this appeared to be an autosomal dominant trait in the father’s family. Dermatoglyphic examination showed the presence of whorls on 7 fingertips and ulnar loops on 3. The atd angle was 50”.A whorl pattern was noted in the right hypothenar area. M-mode echocardiogram showed a patent foramen ovale and peripheral pulmonic stenosis. Renal ultrasonography was normal. Routine chromosome analysis showed an interstitial deletion of 18q.The deletion involved a single dark band
16
Surh et al.
Fig. 2. Chromosomes of patient. To the left is a n idiogram of chromosome 18 at the 550 band stage of resolution (ISCN, 1985). The deletion involves the loss of a single G-positive band in the proximal long arm, either q12.1 or q12.3 (arrows).A G-banded partial karyotype of the patient is shown with the normal chromosome 18 on the left and the deleted 18 on the right.
Fig. 1. Patient at age 30 months.
in the proximal long arm, either q12.1 or q12.3 (Fig. 2). Karyotypes from the parents were normal indicating that this is a de novo event.
DISCUSSION A computer search of the literature showed only 2 other case reports of an interstitial deletion of 18q unassociated with translocations. Both cases may involve the same region but have very different phenotypes. The first report comprised a deletion of q12.3 as well as
adjacent light staining chromatin from q21.1 [Wilson et al., 19793. In that case, a boy with a normal female twin was born a t 32 weeks gestation to a 25-year-old mother and a 28-year-oldfather. His growth parameters were at the 5th to 10th centile, with a large elongated head, ptosis, alternating esotropia, bilateral epicanthal folds, abnormal ears, bilateral cryptorchidism, and reduced muscle strength. Developmental delay was evident from early infancy and a Gesell developmental quotient was 30 to 40 a t 2 years. The second report described an interstitial deletion of q12.2q21.1 in a boy born at term to a 32-year-old mother and 34-year-old father [Wilson and A1 Saadi, 19891.The boy was hypotonic and developmentally delayed with onset of obesity at age 3. His height and weight were above the 97th centiles. He had relatively normal face, normal penis, bilaterally descended testes, and mild hypotonia. He was a withdrawn, easily distractible child, with an I& of 50 and a
TABLE I. Phenotypes Associated With Various del(l8q) Karyotypes* del (qll.lq12.2) or del(18)(q21-qter) del (q12.2q21.1) del (q12.2q21.1) Wilson et al. Wilson et al. Wilson and A1 [1979] [19791 Saaddi [19891 __
Manifestations Growth delay Developmental delay Normal birth weight Paternal age Brachycephaly Dolichocephaly Microcephaly (
Brief Clinical Report Interstitial Deletion of Chromosome 18[del(l8)(ql1.2q12.2or q12.2q21.11 Linda C. Surh, David H. Ledbetter, and Frank Greenberg Institute for Molecular Genetics (L.C.S.,D.H.L., F.G.) and Department of Biochemistry (L.C.S.),Baylor College of Medicine, Houston, Texas A 27-month-oldboy with mild developmental delay, growth delay, strabismus, midface hypoplasia, relative telecanthus, downslanting palpebral fissures, epicanthal folds, dental hypoplasia, and cardiac defects was found to have an interstitial deletion of chromosome 18 involving band q12.1 or q12.3.
KEY
WORDS: chromosome abnormality, chromosome 18
INTRODUCTION We report on a 27-month-oldwhite boy with an interstitial deletion of chromosome 18 involving band q12.1 or q12.3. Although he was previously suspected to have Williams syndrome, further clinical history and detailed physical examination were not consistent with that syndrome. CLINICAL REPORT The propositus (Fig. 1)was born at 38 weeks by dates to a gravida 2, para 1,23-year-old mother and 26-yearold father. The pregnancy was uncomplicated except for oral erythromycin treatment for a respiratory infection at 4 to 5 months’ gestation. He was delivered vaginally with Apgar scores of 3 at one minute, 5 a t 5 min with initial bagging. Oxygen was required for the first 30 hr. He appeared to be at 36 weeks of gestation by examination, with a birth weight of 2,780 g. He went home at 5 days. Breast feeding went well until age 6 months when he was switched to a lactose formula. He then began having multiple ear infections, documented episodes of pneumonia, diarrhea, and reduced weight gain. At age 9 months, lactose intolerance was diagnosed as the cause of his diarrhea. With appropriate diet management, he has had normal bowel movements without constipation. Received for publication March 5, 1990; revision received September 24, 1990. Address reprint requests to Frank Greenberg, M.D., Institute for Molecular Genetics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030.
0 1991 Wiley-Liss, Inc.
Psychomotor development was initially normal with smile at 3 weeks, sitting at 5 months, crawling at 9 months, and drinking from a cup a t 12 months. However, he walked a t 16 months and is not toilet trained at 27 months. He can make simple 3-word sentences and understands simple commands. At 22 months, he had a strabismus repair and wears glasses for hypermetropia. Behaviorly, he had a short attention span and was hyperdistractible. Family history was unremarkable. He was diagnosed as Williams syndrome elsewhere. The mother’s obstetrician referred him at the time of her second pregnancy t o confirm the diagnosis and provide recurrence risk counseling. Chromosome analysis was not previously done. Physical examination at 27 months showed a small, easily distractible male with a head circumference of 48.5 cm, height of 84.2 cm, and weight of 10.8 kg (all parameters 50% for 15 to 20 months). He had frontal bossing with mid-face hypoplasia, relative telecanthus, downslanting palpebral fissures with epicanthal folds. His nasal bridge was flat with a small nose, thin lips, and a normal appearing philtrum. Ears were normal in configuration and position. The palate appeared normal but there was dental hypoplasia of the upper central and lateral incisors with otherwise normal teeth. A grade l16 systolic ejection murmur was present at the right upper sternum. He had Tanner stage 1 male genitalia with bilaterally descended testes. Neurologically, he had intact cranial nerves II-XII, normal muscle tone and strength, and his reflexes were diminished (1+ ) but symmetric. Sensation and cerebellar functions were normal. Although hypoplastic nails were present on fingers and toes, his apparently normal sister also displayed this characteristic and upon further questioning, this appeared to be an autosomal dominant trait in the father’s family. Dermatoglyphic examination showed the presence of whorls on 7 fingertips and ulnar loops on 3. The atd angle was 50”.A whorl pattern was noted in the right hypothenar area. M-mode echocardiogram showed a patent foramen ovale and peripheral pulmonic stenosis. Renal ultrasonography was normal. Routine chromosome analysis showed an interstitial deletion of 18q.The deletion involved a single dark band
16
Surh et al.
Fig. 2. Chromosomes of patient. To the left is a n idiogram of chromosome 18 at the 550 band stage of resolution (ISCN, 1985). The deletion involves the loss of a single G-positive band in the proximal long arm, either q12.1 or q12.3 (arrows).A G-banded partial karyotype of the patient is shown with the normal chromosome 18 on the left and the deleted 18 on the right.
Fig. 1. Patient at age 30 months.
in the proximal long arm, either q12.1 or q12.3 (Fig. 2). Karyotypes from the parents were normal indicating that this is a de novo event.
DISCUSSION A computer search of the literature showed only 2 other case reports of an interstitial deletion of 18q unassociated with translocations. Both cases may involve the same region but have very different phenotypes. The first report comprised a deletion of q12.3 as well as
adjacent light staining chromatin from q21.1 [Wilson et al., 19793. In that case, a boy with a normal female twin was born a t 32 weeks gestation to a 25-year-old mother and a 28-year-oldfather. His growth parameters were at the 5th to 10th centile, with a large elongated head, ptosis, alternating esotropia, bilateral epicanthal folds, abnormal ears, bilateral cryptorchidism, and reduced muscle strength. Developmental delay was evident from early infancy and a Gesell developmental quotient was 30 to 40 a t 2 years. The second report described an interstitial deletion of q12.2q21.1 in a boy born at term to a 32-year-old mother and 34-year-old father [Wilson and A1 Saadi, 19891.The boy was hypotonic and developmentally delayed with onset of obesity at age 3. His height and weight were above the 97th centiles. He had relatively normal face, normal penis, bilaterally descended testes, and mild hypotonia. He was a withdrawn, easily distractible child, with an I& of 50 and a
TABLE I. Phenotypes Associated With Various del(l8q) Karyotypes* del (qll.lq12.2) or del(18)(q21-qter) del (q12.2q21.1) del (q12.2q21.1) Wilson et al. Wilson et al. Wilson and A1 [1979] [19791 Saaddi [19891 __
Manifestations Growth delay Developmental delay Normal birth weight Paternal age Brachycephaly Dolichocephaly Microcephaly (
