750
Brief clinical and laboratory observations
patients with nonidiopathic scoliosis, the search for occult neuromuscular disorders in patients with any type of scoliosis is mandatory. The knowledge that certain n e u r o m u s c u l a r disorders are progressive may also modify surgical therapy or alter its results. The familial character of certain neuromuscular disorders indicates the importance of genetic counseling as well as the possibility of earlier therapeutic intervention in such patients with use of the Milwaukee brace. It was concluded that all patients with scoliosis require careful neurologic evaluation. Associated anomalies and neurologic disorders must be identified early in order to (1) plan appropriate therapy, (2) offer genetic counseling when indicated, (3) establish if progression of neurologic impairment is to be anticipated, and (4) identify those patients for whom risk of operative complications is increased.
Anomalies associated with partial deletion of long arm of chromosome 11 Louie G. Linarelli,* K. Gopalkrishna Pai, Sylvia F. Pan, and Harvey M. Rubin, Pittsburgh, Pa.
A CHILD with mental retardation and multiple congenital anomalies was found to have a partial deletion of the long arm of chromosome No. 11. A modified trypsinGiemsa banding technique 1 was employed to identify the c h r o m o s o m e a b n o r m a l i t y w h e r e c o n v e n t i o n a l staining had failed to identify an abnormality 6 years previously. CASE REPORT M. G., a 12-year-old boy, is the youngest of four children born at 2[8 weeks' gestation to a then 32-year-old mother and 33-year-old father. There was no history of miscarriages. The From the Departments of Pediatrics, Mercy Hospital and Children's Hospital Universityof Pittsburgh School of Medicine, and Radiation Health, Graduate School of Public Health. Supported inpart by the National Foundation-March of Dimes. *Reprint address:Departmentof Pediatrics, MercyHospital Pittsburgh, Pa. 15219.
The Journal of Pediatrics May1975
REFERENCES 1. Robin GC, and Brief LP: Scoliosisin childhood muscular dystrophy, J Bone Joint Surg 53A:466, 1971. 2. Huebert HT, and MacKinnon WB: Syringomyelia and scoliosis, J Bone Joint Surg 51B:338, 1969. 3. Scott JC: Scoliosis and neurofibromatosis, J Bone Joint Surg 47B:240, 1965. 4. Winter RB, Moe JH, and Eilers VE: Congenital scoliosis; a study of 234 patients treated and untreated, J Bone Joint Surg 50A:l, 1968. 5. Balmer GA, and MacEwen GD: The incidence and treatment of scoliosis in cerebral palsy, J Bone Joint Surg 52B:134, 1970. 6. Matson DD: Neurosurgery of Infancy and Childhood, ed 2, Springfield, Ill, Charles C Thomas, Publisher, p 654. 7. Wynne-Davies R: Familial (idiopathic) scoliosis; a family survey, J Bone Joint Surg 50B:24, 1968. 8. Goldstein LA: Current and developing aspects in management of scoliosis, NY State J Med 72:2977, 1972.
parents are unrelated and there is no family history of persons with similar anomalies. The pregnancy was complicated by vaginal bleeding during the third month. The birth weight was 2,353 gm (length not recorded). He was noted at birth to have trigonocephaly, epicanthal folds, bilateral simian creases, and aplasia of the distal phalanx of the third and fourth fingers of the left hand. He developed mild respiratory distress which lasted for 72 hours. Deafness was noted at 2 weeks of age. At 6 weeks of age he underwent surgery for pyloric stenosis which was complicated by a staphylococcal wound abscess. He was noted throughout early childhood to have frequent upper and lower respiratory infections and continual problems with staphylococcal skin infections. A bilateral inguinal herniorrhaphy was performed at 2 years, 8 months of age. A grade 3/6 harsh systolic murmur heard best at the lower left sternal border was first noted at 7 months of age and was felt to be a ventricular septal defect. His developmental milestones were severely delayed and psychologic testing on several occasions confirmed profound mental retardation. Audiometric evaluation demonstrated severe bilateral deafness. On physical examination at 12 years of age his height was 119.4 cm (less than third percentile), weight 24.5 kg (less than third percentile), and head circumference 53.5 cm (forty-fifth percentile). The pertinent physical findings included profound mental retardation, trigonocephaly, hypotelorism, epicanthal folds, bilateral ptosis, downward slanted palpebral fissures, left coloboma, fiat nasal bridge with anteverted nostrils, low-set small anomalous ears, carp-shaped mouth, mild micrognathia, aplasia of the distal phalanx of the left third and fourth fingers, bilateral clinodactyly, shortening of all the toes except the big
Volume 86 Number 5
Brief clinical and laboratory observations
m
-'~(~
751
............................ ~
V Yl
j#
Fig. 1. Full karyotype with trypsin-Giemsa banding. The ~Irrow indicates partial deletion of the long arm of chromosome No. 11. The left column shows the deletion fro m seven additional pairs of chromosome No. 11.
toes, and partial syndactyly of the second and third toes bilaterally. The previously heard murmur was no longer present. Normal laboratory results included complete blood count, urinalysis, and concentrations of fasting blood glucose, blood urea nitrogen, serum electrolytes, cholesterol, protein-bound iodine, calcium, phosphorous, alkaline phosphatase, SGOT, SGPT, total LDH, LDH isozymes, and metabolic screening (ferric chloride, DNPH, cyanide-nitroprusside, mucopolysaccharides by toluidine blue spot test and one-way paper chromotography by butanol: acetic acid: water). Laboratory determinations of humoral immunity which were normal included immunoelectrophoresis, serum protein electropboresis, C 3 and C 4 complement, and Schick test. Determinations of cellular immunity by delayed skin tests with tuberculin, mumps, monilia, and tetanus toxoid gave appropriate responses. Investigations of leukocyte function by quantitative nitrotetrazolium blue dye reduction test in the patient's resting and phagocytosing cells were normal. Roentgenograms at age 5 years, 11 months, demonstrated clinodactyly of the right fifth finger with partial hypoplasia of the middle ptialanx. Clinodactyly of the fifth finger and aplasia of the distal phalanges of the third and fourth fingers and of the fourth middle phalanx were present on the left hand. There
Was marked hypoplasia of the middle phalanges of the second, third, and fifth digits. Spina bifida occulta of L5 was noted at 12 years of age and his bone age was 7 years, 3 months. The cytogenetic studies demonstrated a normal male karyotype by conventional technique in 1967. A partially deleted lolag arm of chromosome No, 11 (46 XY, del (11) (q 22), which was present in all cells analyzed, (Fig. 1) was identified in a repeat chromosomal analysis in 1973 by trypsin-Giemsa banding. 1Chromosomal analysis of each parent was normal. The patient's dermatoglyphics included five arches, four ulnar loops, and one whorl. There was a single palmar simian crease on the left hand. The right hand had two transverse palmar creases. The proximal crease extends across the palm and the distal one is a partial transverse crease. The ATD angles were 50 degrees. DISCUSSION A partial deletion o f the 10ng arm o f c h r o m o s o m e No. 11 was identified by t r y p s i n - G i e m s a banding in a 12year-old b o y w h o was of low birth weight and has growth failure, p r o f o u n d m e n t a l retardation, m u l t i p l e physical anomalies, and f r e q u e n t infections. This is the first reported patient to our k n o w l e d g e with a deletion i n v o l v i n g c h r o m o s o m e No. 11. O n e p r e v i o u s r e p o r t
7$2
Brief clinical and laboratory observations
d e m o n s t r a t e d a m o r e e x t e n s i v e deletion of t h e long arm of one o f the a u t o s o m a l c h r o m o s o m e s in group 6-12 but the exact c h r o m o s o m e was not identified. 2 T h a t patient was a 2-year, 1 0 - m o n t h - o l d girl with m e n t a l retardation, hypertelorism, low-set ears, bilateral clinodactyly, and simian creases. We wish to thank Kenneth Garver, M.D., Mark Steele, M.D., Gilbert Friday, M.D., and David Lee Miller, M.D. for their re-
The Journal of Pediatrics May 1975
view of this patient. We are grateful to Ruth Sorg for her cytogenetic technical assistance and to John Bobik and Caroline Bobik for their biochemical assistance. REFERENCES
1. Seabright M: A rapid banding technique for human chromosomes, Lancet 2:971, 1971. 2. Biscatti G: Parziale delezione delle braccia Lunghe di un cromosoma del gruppo 6-12, Pediatriia 73:660, 1965.
Brief clinical and laboratory observations
patients with nonidiopathic scoliosis, the search for occult neuromuscular disorders in patients with any type of scoliosis is mandatory. The knowledge that certain n e u r o m u s c u l a r disorders are progressive may also modify surgical therapy or alter its results. The familial character of certain neuromuscular disorders indicates the importance of genetic counseling as well as the possibility of earlier therapeutic intervention in such patients with use of the Milwaukee brace. It was concluded that all patients with scoliosis require careful neurologic evaluation. Associated anomalies and neurologic disorders must be identified early in order to (1) plan appropriate therapy, (2) offer genetic counseling when indicated, (3) establish if progression of neurologic impairment is to be anticipated, and (4) identify those patients for whom risk of operative complications is increased.
Anomalies associated with partial deletion of long arm of chromosome 11 Louie G. Linarelli,* K. Gopalkrishna Pai, Sylvia F. Pan, and Harvey M. Rubin, Pittsburgh, Pa.
A CHILD with mental retardation and multiple congenital anomalies was found to have a partial deletion of the long arm of chromosome No. 11. A modified trypsinGiemsa banding technique 1 was employed to identify the c h r o m o s o m e a b n o r m a l i t y w h e r e c o n v e n t i o n a l staining had failed to identify an abnormality 6 years previously. CASE REPORT M. G., a 12-year-old boy, is the youngest of four children born at 2[8 weeks' gestation to a then 32-year-old mother and 33-year-old father. There was no history of miscarriages. The From the Departments of Pediatrics, Mercy Hospital and Children's Hospital Universityof Pittsburgh School of Medicine, and Radiation Health, Graduate School of Public Health. Supported inpart by the National Foundation-March of Dimes. *Reprint address:Departmentof Pediatrics, MercyHospital Pittsburgh, Pa. 15219.
The Journal of Pediatrics May1975
REFERENCES 1. Robin GC, and Brief LP: Scoliosisin childhood muscular dystrophy, J Bone Joint Surg 53A:466, 1971. 2. Huebert HT, and MacKinnon WB: Syringomyelia and scoliosis, J Bone Joint Surg 51B:338, 1969. 3. Scott JC: Scoliosis and neurofibromatosis, J Bone Joint Surg 47B:240, 1965. 4. Winter RB, Moe JH, and Eilers VE: Congenital scoliosis; a study of 234 patients treated and untreated, J Bone Joint Surg 50A:l, 1968. 5. Balmer GA, and MacEwen GD: The incidence and treatment of scoliosis in cerebral palsy, J Bone Joint Surg 52B:134, 1970. 6. Matson DD: Neurosurgery of Infancy and Childhood, ed 2, Springfield, Ill, Charles C Thomas, Publisher, p 654. 7. Wynne-Davies R: Familial (idiopathic) scoliosis; a family survey, J Bone Joint Surg 50B:24, 1968. 8. Goldstein LA: Current and developing aspects in management of scoliosis, NY State J Med 72:2977, 1972.
parents are unrelated and there is no family history of persons with similar anomalies. The pregnancy was complicated by vaginal bleeding during the third month. The birth weight was 2,353 gm (length not recorded). He was noted at birth to have trigonocephaly, epicanthal folds, bilateral simian creases, and aplasia of the distal phalanx of the third and fourth fingers of the left hand. He developed mild respiratory distress which lasted for 72 hours. Deafness was noted at 2 weeks of age. At 6 weeks of age he underwent surgery for pyloric stenosis which was complicated by a staphylococcal wound abscess. He was noted throughout early childhood to have frequent upper and lower respiratory infections and continual problems with staphylococcal skin infections. A bilateral inguinal herniorrhaphy was performed at 2 years, 8 months of age. A grade 3/6 harsh systolic murmur heard best at the lower left sternal border was first noted at 7 months of age and was felt to be a ventricular septal defect. His developmental milestones were severely delayed and psychologic testing on several occasions confirmed profound mental retardation. Audiometric evaluation demonstrated severe bilateral deafness. On physical examination at 12 years of age his height was 119.4 cm (less than third percentile), weight 24.5 kg (less than third percentile), and head circumference 53.5 cm (forty-fifth percentile). The pertinent physical findings included profound mental retardation, trigonocephaly, hypotelorism, epicanthal folds, bilateral ptosis, downward slanted palpebral fissures, left coloboma, fiat nasal bridge with anteverted nostrils, low-set small anomalous ears, carp-shaped mouth, mild micrognathia, aplasia of the distal phalanx of the left third and fourth fingers, bilateral clinodactyly, shortening of all the toes except the big
Volume 86 Number 5
Brief clinical and laboratory observations
m
-'~(~
751
............................ ~
V Yl
j#
Fig. 1. Full karyotype with trypsin-Giemsa banding. The ~Irrow indicates partial deletion of the long arm of chromosome No. 11. The left column shows the deletion fro m seven additional pairs of chromosome No. 11.
toes, and partial syndactyly of the second and third toes bilaterally. The previously heard murmur was no longer present. Normal laboratory results included complete blood count, urinalysis, and concentrations of fasting blood glucose, blood urea nitrogen, serum electrolytes, cholesterol, protein-bound iodine, calcium, phosphorous, alkaline phosphatase, SGOT, SGPT, total LDH, LDH isozymes, and metabolic screening (ferric chloride, DNPH, cyanide-nitroprusside, mucopolysaccharides by toluidine blue spot test and one-way paper chromotography by butanol: acetic acid: water). Laboratory determinations of humoral immunity which were normal included immunoelectrophoresis, serum protein electropboresis, C 3 and C 4 complement, and Schick test. Determinations of cellular immunity by delayed skin tests with tuberculin, mumps, monilia, and tetanus toxoid gave appropriate responses. Investigations of leukocyte function by quantitative nitrotetrazolium blue dye reduction test in the patient's resting and phagocytosing cells were normal. Roentgenograms at age 5 years, 11 months, demonstrated clinodactyly of the right fifth finger with partial hypoplasia of the middle ptialanx. Clinodactyly of the fifth finger and aplasia of the distal phalanges of the third and fourth fingers and of the fourth middle phalanx were present on the left hand. There
Was marked hypoplasia of the middle phalanges of the second, third, and fifth digits. Spina bifida occulta of L5 was noted at 12 years of age and his bone age was 7 years, 3 months. The cytogenetic studies demonstrated a normal male karyotype by conventional technique in 1967. A partially deleted lolag arm of chromosome No, 11 (46 XY, del (11) (q 22), which was present in all cells analyzed, (Fig. 1) was identified in a repeat chromosomal analysis in 1973 by trypsin-Giemsa banding. 1Chromosomal analysis of each parent was normal. The patient's dermatoglyphics included five arches, four ulnar loops, and one whorl. There was a single palmar simian crease on the left hand. The right hand had two transverse palmar creases. The proximal crease extends across the palm and the distal one is a partial transverse crease. The ATD angles were 50 degrees. DISCUSSION A partial deletion o f the 10ng arm o f c h r o m o s o m e No. 11 was identified by t r y p s i n - G i e m s a banding in a 12year-old b o y w h o was of low birth weight and has growth failure, p r o f o u n d m e n t a l retardation, m u l t i p l e physical anomalies, and f r e q u e n t infections. This is the first reported patient to our k n o w l e d g e with a deletion i n v o l v i n g c h r o m o s o m e No. 11. O n e p r e v i o u s r e p o r t
7$2
Brief clinical and laboratory observations
d e m o n s t r a t e d a m o r e e x t e n s i v e deletion of t h e long arm of one o f the a u t o s o m a l c h r o m o s o m e s in group 6-12 but the exact c h r o m o s o m e was not identified. 2 T h a t patient was a 2-year, 1 0 - m o n t h - o l d girl with m e n t a l retardation, hypertelorism, low-set ears, bilateral clinodactyly, and simian creases. We wish to thank Kenneth Garver, M.D., Mark Steele, M.D., Gilbert Friday, M.D., and David Lee Miller, M.D. for their re-
The Journal of Pediatrics May 1975
view of this patient. We are grateful to Ruth Sorg for her cytogenetic technical assistance and to John Bobik and Caroline Bobik for their biochemical assistance. REFERENCES
1. Seabright M: A rapid banding technique for human chromosomes, Lancet 2:971, 1971. 2. Biscatti G: Parziale delezione delle braccia Lunghe di un cromosoma del gruppo 6-12, Pediatriia 73:660, 1965.
