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Sagittal craniostenosis: Fetal head constraint as one possible cause
Volume 95 Number 5, part 1
B r i e f clinical and laboratory observations
747
Sagittal craniostenosis." Fetal head constraint as one possible cause John M. Graham, Jr., M.D., Margot deSaxe, and David W. Smith, M.D.,* Seattle, Wash.
THE SAGITTAL SUTURE is the most commonly involved suture among all patients with craniostenosis, occurring with an estimated incidence of 0.4 per 1,000 live births? Premature closure of the sagittal suture is usually a sporadic congenital anomaly of unknown etiology in an otherwise normal child. We recently evaluated such an infant, whose mother had noted descent of her abdominal silhouette two to three months before delivery. She had the sensation that the fetal head had become "wedged" in her pelvis, and had severe symptoms of lower pelvic pressure and discomfort that caused marked difficulties in ambulation during the last six weeks of gestation. Her obstetrician noted a lower than expected fundal height throughout pregnancy, in the presence of normal fetal size and activity. This unusual prenatal history caused us to question whether head constraint in late fetal life could be one causative factor in the genesis of sagittal craniostenosis. This report sets forth the findings relative to possible prenatal head constraint in 16 instances-of congenital sagittal craniostenosis. PATIENTS
AND METHODS
Patients were selected by a review of the medical records at the University of Washington Hospital and the Children's Orthopedic Hospital and Medical Center for intances of isolated sagittal craniostenosis in which there was no evidence of associated malformations or mental deficiency, plus a negative family history for craniostenosis. Of 31 cases ascertained, we were able to interview 16 mothers concerning their prenatal history, noting in particular the duration and character of fetal head descent, symptoms of lower pelvic pressure and discomfort, and evidence of cephalopelvic disproportion. These From the Dysmorphology Unit, Department of Pediatrics, Child Development and Mental Retardation Center, and the Center for Inherited Diseases, University of Washington School of Medicine. Supported b), Bureau of Community Health Services, Health Services Administration, Public Health Service, Department of Health, Education and Welfare, Project 913," National Institutes of Health Grant No. HD 05961; Public Health Service Grant No. GM 15253; and Research Fellowship Grant, U.S. Public Health Service, National Institutes of Health No. HD-O04-04. *Reprint address: Department of Pediatrics RD-20, University of Washington, School of Medicine, Seattle, WA 98195.
0022-3476/79/110747 + 04500.40/0 9 1979 The C. V. Mosby Co.
interviews were further supplemented by medical documentation from records and roentgenograms. The mothers of the remaining fifteen patients with isolated sagittal craniostenosis were either dead or lost to follow-up. A survey of the time of lightening in 130 women who had delivered a normal term infant was undertaken. The term "lightening" was defined to those mothers as a realization that the fetus had "dropped" into the lower pelvis, associated with a change in the mother's abdominal silhouette and usually a sensation of pressure deep in the pelvis. Estimates were rounded off to the nearest week, and data for primiparous mothers were separated from those for multiparous mothers. RESULTS The gestational and perinatal historical features of these 16 pregnancies are summarized in the Table. Eight of these women (cases 1 to 8) gave a history of early descent of their abdominal silhouette and/or severe pelvic pressure and discomfort during the last one to three months of gestation. Four of these mothers noted pain radiating down their legs, and two others limited their ambulation because of the degree of pelvic pressure and discomfort. These symptoms were interpreted as a consequence of early descent of the fetal head into the lower pelvis. Histologic examination of synostotic sagittal suture tissues removed during partial calvariectomy for correction of headshape in two of these infants who appeared to have experienced fetal head constraint (Patients 1 and 2) revealed significant differences from normal suture tissue. There was thickened bone in the area of the fused suture. The endocranial surface revealed resorption, while there was active proliferation and deposition of bone along the ectocraniat surface. In contrast, suture tissue from autopsled neonates with normal heads showed thin bone at the suture margins and flattening of the endocranial contour through bone deposition. The history of early lightening six weeks or more prior to delivery in five of the mothers of infants with sagittal craniostenosis (31%) was in excess of that ascertained from a sample of 130 women delivering normal offspring. The latter survey indicated that only 10% (seven of 69) of primiparous and 2% (one of 61) of multiparous mothers perceived lightening four or more weeks before delivery. None of these women reported any severe pressure or
Brief clinical and laboratory observations
748
The Journal of Pediatrics November 1979
Table. Prenatal factors in 16 cases of isolated sagittal craniostenosis
Sex
Parity
Gestation
Time of lightening prior to delivery
1
F
2
40 wk
31/2 to 4 mo
6-8 wk
+ + +
2 3 4 5 6
M M M F M
3 2 3 3 2
35 wk 411k wk Term Term 37 wk
2-3 mo 2-3 mo ? ?
2-3 mo 2-3 mo lmo lmo 1 mo
+ + + + + + +++ +++ +++
7 8 9
F M M
2 1 1
Term 411/2 wk Term
6 wk 6 wk
10
M
1
9V>10 mo
11
M
4
431A wk
12
M
1
40 wk
13
M
1
Term
14
M
2
38-39 wk
15 16
M M
2 1
39 wk Term
Case
Pelvic pressure and discomfort Duration
Cephalopelvic disproportion
Birth presentation Vertex
+
+
Vertex Vertex ? brow Vertex Occiput posterior Vertex Face Brow
+
+
Vertex
+
+
Vertex
+
Vertex
9
+
Vertex
9
+
? occiput posterior Vertex Vertex
9
wk
---
-
Late gestation Late gestation Late gestation
1
Severity
1
wk
++
9
Mode of delivery Repeat cesarean section Vaginal Vaginal Forceps vaginal Vaginal Forceps vaginal Forceps vaginal Forceps vaginal Emergency cesarean section Forceps vaginal Emergency cesarean section Emergency cesarean section Emergency cesarean section Forceps vaginal Vaginal Forceps vaginal
= Negative; ? = no change in profile noted; + = present; + + = moderately severe; + + + = severe. discomfort in association with early lightening, a n d n o n e of their infants h a d craniostenosis. Eight of the 16 m o t h e r s of infants with sagittal craniostenosis recalled n o signs o f early descent of the fetal h e a d into the lower pelvis. O f these women, six h a d evidence of cephalopelvic d i s p r o p o r t i o n with failure of the head to progress during labor. This necessitated delivery by emergency cesarean section in four of the mothers a n d application o f midforceps for delivery i n t h e r e m a i n i n g two. One of the mothers h a d a negative history for either early d r o p p i n g o f the fetal head or cephalopelvic disproportion, and her i n f a n t was the only child in w h o m the craniostenosis resolved s p o n t a n e o u s l y without surgery, despite previous clinical a n d r o e n t g e n o g r a p h i c evidence for sagittal craniostenosis. DISCUSSION Normally, the cranial sutures are o p e n at birth, interdigitated by 7~k m o n t h s , a n d not comp!etely fused until the fourth d e c a d e 5 T h e d u r a appears { o b e the guiding tissue in the m o r p h o g e n e s i s o f the calvaiZ'ium a n d its m a j o r sutures. T h e sites o f ossification are d e t e r m i n e d by growth stretch tensile forces in the dura, a n d m e m b r a n o u s ossification begins m i d w a y between dural reflections a n d
spreads toward those reflections. Thus, sutures r e m a i n over m a j o r dural reflections as expansible connective tissue joints that are m a i n t a i n e d t h r o u g h growth stretch tensile forces generated by the developing brain.:'- ~ T h e patency of the sagittal suture, which forms in relation to the underlying dural reflection o f the falx cerebri, is contingent on persistent lateral growth stretch at the suture site. Lack o f growth stretch m a y occur secondary to a deficit o f b r a i n growth, as in p r i m a r y microcephaly, or vh~y result from excessive decompression of increased intracranial pressure via early ventriculovenous s h u n t i n g for h y d r o c e p h a l u s ? In b o t h instances, secondary craniosynostosis is liable to occur, t h o u g h reliable incidence figures are lacking. Persing and J a n e '~ h a v e recently d e m o n s t r a t e d that sutural immobilization, t h r o u g h the application of methyl-cyanoacrylic adhesive to sutdres ' i n 9-day-old rabbits, results in secondary craniosyhostosis across the sutures where growth stretch was constrained. W e hypothesize that, in a similar fashion, prolonged external constraint of the fetal head in the lateral d i m e n s i o n m a y limit growth stretch at the sagittal suture, resulting in an abutted, ridged sagittal suture. Such a ridge is usually p a l p a b l e a n d tends to be most p r o m i n e n t along the posterior p o r t i o n o f the sagittal
Volume 95 Number 5, part 1
suture, as shown in the Figure. This is the plane of the widest lateral cranial diameter, between the parietal eminences, where maximal lateral growth restraint would be expected to occur. Our data seem to be compatible with the hypothesis that prolonged constraint of the fetal head may be one factor in the genesis of sagittal craniostenosis. The head constraint would be the presumed consequence of the fetal head descending into the maternal pelvis and there becoming relatively constricted in terms of lateral growth. As an alternative hypothesis, it could be suggested that early sagittal craniostenosis, with consequent scaphocephalic elongation of the fetal head shape, might predispose toward early descent of the fetal head into the pelvis. It seems more probable that prior scaphocephaly would actually reduce the likelihood of early descent of the fetal head. Among the eight mothers of children with sagittal craniostenosis who had not noted early lightening a n d / o r pelvic pressure and discomfort, there was a high incidence of cephalopelvic disporportion, which actually impeded the descent of the fetal head and contributed to a high frequency of emergency cesarean section of forcepsassisted deliveries. An excess of aberrant birth presentations was also noted among these infants with sagittal craniostenosis. These unusual delivery characteristics probably reflect the impact of a seaphocephalic head shape with a less malleable, fused sagittal suture, and render less plausible the alternate hypothesis that scaphocephaly might facilitate early descent of the fetal head. It was not possible to obtain reliable information concerning the role played by the shape of the mother's pelvis in any of these patients with sagittal craniostenosis, but this might be an important factor. The platypelloid type of pelvis demonstrates the shortest anteroposterior diameter and the widest transverse diameter, and therefore would be most likely to predispose toward lateral head constraint with early fetal head descent. This is the least common type of pelvic shape, occurring in about 2 to 3% of women.: Acknowledgement of fetal head constraint as one possible cause for sagittal craniostenosis might help to explain some of the observed phenomena noted in children with this type of craniostenosis. (1) The fact that sagittal craniostenosis most commonly occurs in otherwise normal individuals would be compatible with the thesis that a significant proportion of cases are deformational, the consequence of extrinsic molding forces in an otherwise normal fetus. (2) The striking excess of affected males versus females, 78% in the series of Hunter and Rudd 1 and 83% in the present small series, might relate to the more rapid rate of growth and larger head size of the
Brief clinical and laboratory observations
749
Figure. Sagittal craniostenosis in a 6-month-old child with ridging of the posterior sagittal sutm'e most prominent between the parietal eminences. male fetus versus the female fetus during the last trimester of gestation. Constraint deformations are more likely to occur in a larger fetus, and constraint-induced plagiocephalic craniofacial deformation is also more common in the male than in the female. It should be emphasized that fetal head constraint is suggested as only one possible cause for sagittal craniostenosis. Whether this potential mode of etiology should dictate any changes in management remains to be determined. Before considering the implications for parental counseling, the role of maternal pelvic shape and its inheritance needs further clarification. Head constraint in utero should be considered as one possible causal factor for patients with sagittal craniostenosis. Other possible etiologies for craniostenosis might include deficits in brain growth, primary problems in mesenchymal tissues that remain unspecified at this time, and metabolic derangements such as hyperthyroidism, rickets, and hypercalcemia. These causes should also be given careful consideration during the initial evaluation of any child with craniostenosis. We thank Ms. Jayne Moeller of the Children's Orthopedic Hospital and Medical Center Records Department and Ms. Anne Gregor of the University Hospital Medical Reco~TdsDepartment for their assistance. We also thank Dr. John Loeser of the University Hospital Neurosurgery Department and Dr. Timothy Stuntz of Children's Orthopedic Hospital and Medical Center for providing access to further case materials and surgical specimens. These specimens were processed and examined by Drs. Ben Moffett and Leena Koskinen-Moffett of the University of Wash-
750
B r i e f cfinical a n d laboratory observations
ington School o f Dentistry, and for this assistance, we are especially grateful. We are also indebted to Dr. Marvin Miller and Ms. Mary Ann Sedgwick Harvey for editorial advice and to Ms. Jane Fowler, Ms. Karin McDougall, and Ms. Jill Wolcott for secretarial assistance.
REFERENCES 1. Hunter AGW, and Rudd NL: Craniosynostosis I: Sagittal synostosis; its genetics and associated clinical findings in 214 patients who lacked involvement of the coronal suture(s), Teratology 14:185, 1976. 2. Freeman JM, and BorkowfS: Craniostenosis: Review of the
The Journal of Pediatrics November 1979
3. 4. 5.
6. 7.
literature and report of thirty-four cases, Pediatrics 30:57, 1962. Moss ML: The pathogenesis of premature cranial synostosis in man, Acta Anat (Basel) 37:351, 1959. Smith DW, and TOndury G: Origins o f the calvaria and its sutures, Am J Dis Child 132:662, 1978. Andersson H: Craniosynostosis as a complication after operation for hydrocephalus, Acta Paediatr Scand 55:192, 1966. Persing JA, and Jane JA: University of Virginia School of Medicine, personal communication. Hellman LM, and Pritchard JA: in Williams obstetrics, ed 14, New York, 1971, Appleton-Century-Crofts, p 316.
Galactokinase deficiency and mental retardation Stanton Segal, M.D.,* Philadelphia, Pa, Joel Y. Rutman, M.D., and George W. Frimpter, M.D., San Antonio, Texas
IN CONTRAST TO t h e s y n d r o m e o f g a l a c t o s e m i a associated with g a l a c t o s e - l - p h o s p h a t e uridyl t r a n s f e r a s e deficiency, the e m e r g e n t clinical p i c t u r e o f g a l a c t o s e m i a o w i n g to g a l a c t o k i n a s e deficiency h a s b e e n l i m i t e d to cataracts w i t h o u t m e n t a l r e t a r d a t i o n or o t h e r m a n i f e s t a tion o f galactose toxicity. 1' '-' W e have s t u d i e d two b r o t h e r s with g a l a c t o k i n a s e deficiency w h o , in a d d i t i o n to cataracts, h a v e severe m e n t a l r e t a r d a t i o n . T h e i r d e s c r i p t i o n is d e t a i l e d in this report.
CASE REPORT Patient 1. The propositus is a 13-year-old boy of nonconsanguineous parents of northern European extraction whose pre- and postnatal courses were normal. He sat at 11 months and walked at 16 months. At age 3 years he was noted to have bilateral cataracts. Bladder control was n9t achieved until 6 years and bowel training until 9 years. He remains unable to talk although hearing is normal. He has never had seizures, jaundice, anemia, or nausea and vomiting while on a normal galactosecontaining diet. Eye examination disclosed multicentric, mottled, very dense cataracts bilaterally. Except for generalized clumsiFrom the Department of Pediatrics, University of Pennsylvania School of Medicine, and Children's Hospital of Philadelphia: and the Santa Rosa Children's Hospital, Santa Rosa Medical Center," and the Department of Medicine, Univers#y of Texas Health Science Center and Veteran's.7; Administration Hospital. Supported by grant HD 08536 f/om the National Institutes of Health. *Reprint address: Children's Hospital of Philadelphia, 34th St. and Civic Center Blvd., Philadelphia. PA 19104.
ness, general physi(al and neurologic examinations were unremarkable. There was no hepatomegaly. He communicated by pointing and gesture. He required help in all activities of daily living. Psychologic testing at age 8 years showed few scorable responses even at the 2-year level. A Stanford-Binet test at age 11 years, 2 months, showed a mental age of 3 years, 8 months. Blood chemistry values were normal except for a blood galactose concentration of 95 mg/dl. Results of liver function tests were normal. Quantitative ion exchange amino acid chromatography of urine and plasma revealed no abnormality. No abnormal organic acids were present in the urine. Patient 2. The brother had a normal pre- and postnatal course. He sat at 6 to 7 months and walked at 16 months. At 8 years of age he was unable to dress or feed himself, had no speech, and was not toilet-trained. Bilateral cataracts were first noted at 3% years. He has had several operations for cataracts on both eyes with visual acuity now 20/50 in both eyes. Hearing has been normal. At age 6 ye~'~s he had a brief grand mal seizure; an electroencephalogram showed spike discharges from the right hemisphere. He has been free of seizures since receiving phenobarbital. The general and neurologic examinations have been normal except for his mental status. Vineland Social Maturity Scale at age 6 years gave a social age of 2 years. He was unable to perform any tasks on the Stanford-Binet, even at the two-year level, psychologists have indicated that the mental retardation present m both boys is independent of visual loss. Results of an urine screen using Clinitest and glucose oxidase were negative, as were results of tests for amino and organic acids. The parents have been noted by multiple observers to be solicitous of these boys' welfare and to stimulate their development adequately. An older sister, age 15, and the parents are of normal intelligence and do not have cataracts. In the Table are shown the values of red cel ! galactokinase:' and d
.
9
0022-3476/79/110750+03500.30/0 9 1979 The C. V. Mosby Co.
B r i e f clinical and laboratory observations
747
Sagittal craniostenosis." Fetal head constraint as one possible cause John M. Graham, Jr., M.D., Margot deSaxe, and David W. Smith, M.D.,* Seattle, Wash.
THE SAGITTAL SUTURE is the most commonly involved suture among all patients with craniostenosis, occurring with an estimated incidence of 0.4 per 1,000 live births? Premature closure of the sagittal suture is usually a sporadic congenital anomaly of unknown etiology in an otherwise normal child. We recently evaluated such an infant, whose mother had noted descent of her abdominal silhouette two to three months before delivery. She had the sensation that the fetal head had become "wedged" in her pelvis, and had severe symptoms of lower pelvic pressure and discomfort that caused marked difficulties in ambulation during the last six weeks of gestation. Her obstetrician noted a lower than expected fundal height throughout pregnancy, in the presence of normal fetal size and activity. This unusual prenatal history caused us to question whether head constraint in late fetal life could be one causative factor in the genesis of sagittal craniostenosis. This report sets forth the findings relative to possible prenatal head constraint in 16 instances-of congenital sagittal craniostenosis. PATIENTS
AND METHODS
Patients were selected by a review of the medical records at the University of Washington Hospital and the Children's Orthopedic Hospital and Medical Center for intances of isolated sagittal craniostenosis in which there was no evidence of associated malformations or mental deficiency, plus a negative family history for craniostenosis. Of 31 cases ascertained, we were able to interview 16 mothers concerning their prenatal history, noting in particular the duration and character of fetal head descent, symptoms of lower pelvic pressure and discomfort, and evidence of cephalopelvic disproportion. These From the Dysmorphology Unit, Department of Pediatrics, Child Development and Mental Retardation Center, and the Center for Inherited Diseases, University of Washington School of Medicine. Supported b), Bureau of Community Health Services, Health Services Administration, Public Health Service, Department of Health, Education and Welfare, Project 913," National Institutes of Health Grant No. HD 05961; Public Health Service Grant No. GM 15253; and Research Fellowship Grant, U.S. Public Health Service, National Institutes of Health No. HD-O04-04. *Reprint address: Department of Pediatrics RD-20, University of Washington, School of Medicine, Seattle, WA 98195.
0022-3476/79/110747 + 04500.40/0 9 1979 The C. V. Mosby Co.
interviews were further supplemented by medical documentation from records and roentgenograms. The mothers of the remaining fifteen patients with isolated sagittal craniostenosis were either dead or lost to follow-up. A survey of the time of lightening in 130 women who had delivered a normal term infant was undertaken. The term "lightening" was defined to those mothers as a realization that the fetus had "dropped" into the lower pelvis, associated with a change in the mother's abdominal silhouette and usually a sensation of pressure deep in the pelvis. Estimates were rounded off to the nearest week, and data for primiparous mothers were separated from those for multiparous mothers. RESULTS The gestational and perinatal historical features of these 16 pregnancies are summarized in the Table. Eight of these women (cases 1 to 8) gave a history of early descent of their abdominal silhouette and/or severe pelvic pressure and discomfort during the last one to three months of gestation. Four of these mothers noted pain radiating down their legs, and two others limited their ambulation because of the degree of pelvic pressure and discomfort. These symptoms were interpreted as a consequence of early descent of the fetal head into the lower pelvis. Histologic examination of synostotic sagittal suture tissues removed during partial calvariectomy for correction of headshape in two of these infants who appeared to have experienced fetal head constraint (Patients 1 and 2) revealed significant differences from normal suture tissue. There was thickened bone in the area of the fused suture. The endocranial surface revealed resorption, while there was active proliferation and deposition of bone along the ectocraniat surface. In contrast, suture tissue from autopsled neonates with normal heads showed thin bone at the suture margins and flattening of the endocranial contour through bone deposition. The history of early lightening six weeks or more prior to delivery in five of the mothers of infants with sagittal craniostenosis (31%) was in excess of that ascertained from a sample of 130 women delivering normal offspring. The latter survey indicated that only 10% (seven of 69) of primiparous and 2% (one of 61) of multiparous mothers perceived lightening four or more weeks before delivery. None of these women reported any severe pressure or
Brief clinical and laboratory observations
748
The Journal of Pediatrics November 1979
Table. Prenatal factors in 16 cases of isolated sagittal craniostenosis
Sex
Parity
Gestation
Time of lightening prior to delivery
1
F
2
40 wk
31/2 to 4 mo
6-8 wk
+ + +
2 3 4 5 6
M M M F M
3 2 3 3 2
35 wk 411k wk Term Term 37 wk
2-3 mo 2-3 mo ? ?
2-3 mo 2-3 mo lmo lmo 1 mo
+ + + + + + +++ +++ +++
7 8 9
F M M
2 1 1
Term 411/2 wk Term
6 wk 6 wk
10
M
1
9V>10 mo
11
M
4
431A wk
12
M
1
40 wk
13
M
1
Term
14
M
2
38-39 wk
15 16
M M
2 1
39 wk Term
Case
Pelvic pressure and discomfort Duration
Cephalopelvic disproportion
Birth presentation Vertex
+
+
Vertex Vertex ? brow Vertex Occiput posterior Vertex Face Brow
+
+
Vertex
+
+
Vertex
+
Vertex
9
+
Vertex
9
+
? occiput posterior Vertex Vertex
9
wk
---
-
Late gestation Late gestation Late gestation
1
Severity
1
wk
++
9
Mode of delivery Repeat cesarean section Vaginal Vaginal Forceps vaginal Vaginal Forceps vaginal Forceps vaginal Forceps vaginal Emergency cesarean section Forceps vaginal Emergency cesarean section Emergency cesarean section Emergency cesarean section Forceps vaginal Vaginal Forceps vaginal
= Negative; ? = no change in profile noted; + = present; + + = moderately severe; + + + = severe. discomfort in association with early lightening, a n d n o n e of their infants h a d craniostenosis. Eight of the 16 m o t h e r s of infants with sagittal craniostenosis recalled n o signs o f early descent of the fetal h e a d into the lower pelvis. O f these women, six h a d evidence of cephalopelvic d i s p r o p o r t i o n with failure of the head to progress during labor. This necessitated delivery by emergency cesarean section in four of the mothers a n d application o f midforceps for delivery i n t h e r e m a i n i n g two. One of the mothers h a d a negative history for either early d r o p p i n g o f the fetal head or cephalopelvic disproportion, and her i n f a n t was the only child in w h o m the craniostenosis resolved s p o n t a n e o u s l y without surgery, despite previous clinical a n d r o e n t g e n o g r a p h i c evidence for sagittal craniostenosis. DISCUSSION Normally, the cranial sutures are o p e n at birth, interdigitated by 7~k m o n t h s , a n d not comp!etely fused until the fourth d e c a d e 5 T h e d u r a appears { o b e the guiding tissue in the m o r p h o g e n e s i s o f the calvaiZ'ium a n d its m a j o r sutures. T h e sites o f ossification are d e t e r m i n e d by growth stretch tensile forces in the dura, a n d m e m b r a n o u s ossification begins m i d w a y between dural reflections a n d
spreads toward those reflections. Thus, sutures r e m a i n over m a j o r dural reflections as expansible connective tissue joints that are m a i n t a i n e d t h r o u g h growth stretch tensile forces generated by the developing brain.:'- ~ T h e patency of the sagittal suture, which forms in relation to the underlying dural reflection o f the falx cerebri, is contingent on persistent lateral growth stretch at the suture site. Lack o f growth stretch m a y occur secondary to a deficit o f b r a i n growth, as in p r i m a r y microcephaly, or vh~y result from excessive decompression of increased intracranial pressure via early ventriculovenous s h u n t i n g for h y d r o c e p h a l u s ? In b o t h instances, secondary craniosynostosis is liable to occur, t h o u g h reliable incidence figures are lacking. Persing and J a n e '~ h a v e recently d e m o n s t r a t e d that sutural immobilization, t h r o u g h the application of methyl-cyanoacrylic adhesive to sutdres ' i n 9-day-old rabbits, results in secondary craniosyhostosis across the sutures where growth stretch was constrained. W e hypothesize that, in a similar fashion, prolonged external constraint of the fetal head in the lateral d i m e n s i o n m a y limit growth stretch at the sagittal suture, resulting in an abutted, ridged sagittal suture. Such a ridge is usually p a l p a b l e a n d tends to be most p r o m i n e n t along the posterior p o r t i o n o f the sagittal
Volume 95 Number 5, part 1
suture, as shown in the Figure. This is the plane of the widest lateral cranial diameter, between the parietal eminences, where maximal lateral growth restraint would be expected to occur. Our data seem to be compatible with the hypothesis that prolonged constraint of the fetal head may be one factor in the genesis of sagittal craniostenosis. The head constraint would be the presumed consequence of the fetal head descending into the maternal pelvis and there becoming relatively constricted in terms of lateral growth. As an alternative hypothesis, it could be suggested that early sagittal craniostenosis, with consequent scaphocephalic elongation of the fetal head shape, might predispose toward early descent of the fetal head into the pelvis. It seems more probable that prior scaphocephaly would actually reduce the likelihood of early descent of the fetal head. Among the eight mothers of children with sagittal craniostenosis who had not noted early lightening a n d / o r pelvic pressure and discomfort, there was a high incidence of cephalopelvic disporportion, which actually impeded the descent of the fetal head and contributed to a high frequency of emergency cesarean section of forcepsassisted deliveries. An excess of aberrant birth presentations was also noted among these infants with sagittal craniostenosis. These unusual delivery characteristics probably reflect the impact of a seaphocephalic head shape with a less malleable, fused sagittal suture, and render less plausible the alternate hypothesis that scaphocephaly might facilitate early descent of the fetal head. It was not possible to obtain reliable information concerning the role played by the shape of the mother's pelvis in any of these patients with sagittal craniostenosis, but this might be an important factor. The platypelloid type of pelvis demonstrates the shortest anteroposterior diameter and the widest transverse diameter, and therefore would be most likely to predispose toward lateral head constraint with early fetal head descent. This is the least common type of pelvic shape, occurring in about 2 to 3% of women.: Acknowledgement of fetal head constraint as one possible cause for sagittal craniostenosis might help to explain some of the observed phenomena noted in children with this type of craniostenosis. (1) The fact that sagittal craniostenosis most commonly occurs in otherwise normal individuals would be compatible with the thesis that a significant proportion of cases are deformational, the consequence of extrinsic molding forces in an otherwise normal fetus. (2) The striking excess of affected males versus females, 78% in the series of Hunter and Rudd 1 and 83% in the present small series, might relate to the more rapid rate of growth and larger head size of the
Brief clinical and laboratory observations
749
Figure. Sagittal craniostenosis in a 6-month-old child with ridging of the posterior sagittal sutm'e most prominent between the parietal eminences. male fetus versus the female fetus during the last trimester of gestation. Constraint deformations are more likely to occur in a larger fetus, and constraint-induced plagiocephalic craniofacial deformation is also more common in the male than in the female. It should be emphasized that fetal head constraint is suggested as only one possible cause for sagittal craniostenosis. Whether this potential mode of etiology should dictate any changes in management remains to be determined. Before considering the implications for parental counseling, the role of maternal pelvic shape and its inheritance needs further clarification. Head constraint in utero should be considered as one possible causal factor for patients with sagittal craniostenosis. Other possible etiologies for craniostenosis might include deficits in brain growth, primary problems in mesenchymal tissues that remain unspecified at this time, and metabolic derangements such as hyperthyroidism, rickets, and hypercalcemia. These causes should also be given careful consideration during the initial evaluation of any child with craniostenosis. We thank Ms. Jayne Moeller of the Children's Orthopedic Hospital and Medical Center Records Department and Ms. Anne Gregor of the University Hospital Medical Reco~TdsDepartment for their assistance. We also thank Dr. John Loeser of the University Hospital Neurosurgery Department and Dr. Timothy Stuntz of Children's Orthopedic Hospital and Medical Center for providing access to further case materials and surgical specimens. These specimens were processed and examined by Drs. Ben Moffett and Leena Koskinen-Moffett of the University of Wash-
750
B r i e f cfinical a n d laboratory observations
ington School o f Dentistry, and for this assistance, we are especially grateful. We are also indebted to Dr. Marvin Miller and Ms. Mary Ann Sedgwick Harvey for editorial advice and to Ms. Jane Fowler, Ms. Karin McDougall, and Ms. Jill Wolcott for secretarial assistance.
REFERENCES 1. Hunter AGW, and Rudd NL: Craniosynostosis I: Sagittal synostosis; its genetics and associated clinical findings in 214 patients who lacked involvement of the coronal suture(s), Teratology 14:185, 1976. 2. Freeman JM, and BorkowfS: Craniostenosis: Review of the
The Journal of Pediatrics November 1979
3. 4. 5.
6. 7.
literature and report of thirty-four cases, Pediatrics 30:57, 1962. Moss ML: The pathogenesis of premature cranial synostosis in man, Acta Anat (Basel) 37:351, 1959. Smith DW, and TOndury G: Origins o f the calvaria and its sutures, Am J Dis Child 132:662, 1978. Andersson H: Craniosynostosis as a complication after operation for hydrocephalus, Acta Paediatr Scand 55:192, 1966. Persing JA, and Jane JA: University of Virginia School of Medicine, personal communication. Hellman LM, and Pritchard JA: in Williams obstetrics, ed 14, New York, 1971, Appleton-Century-Crofts, p 316.
Galactokinase deficiency and mental retardation Stanton Segal, M.D.,* Philadelphia, Pa, Joel Y. Rutman, M.D., and George W. Frimpter, M.D., San Antonio, Texas
IN CONTRAST TO t h e s y n d r o m e o f g a l a c t o s e m i a associated with g a l a c t o s e - l - p h o s p h a t e uridyl t r a n s f e r a s e deficiency, the e m e r g e n t clinical p i c t u r e o f g a l a c t o s e m i a o w i n g to g a l a c t o k i n a s e deficiency h a s b e e n l i m i t e d to cataracts w i t h o u t m e n t a l r e t a r d a t i o n or o t h e r m a n i f e s t a tion o f galactose toxicity. 1' '-' W e have s t u d i e d two b r o t h e r s with g a l a c t o k i n a s e deficiency w h o , in a d d i t i o n to cataracts, h a v e severe m e n t a l r e t a r d a t i o n . T h e i r d e s c r i p t i o n is d e t a i l e d in this report.
CASE REPORT Patient 1. The propositus is a 13-year-old boy of nonconsanguineous parents of northern European extraction whose pre- and postnatal courses were normal. He sat at 11 months and walked at 16 months. At age 3 years he was noted to have bilateral cataracts. Bladder control was n9t achieved until 6 years and bowel training until 9 years. He remains unable to talk although hearing is normal. He has never had seizures, jaundice, anemia, or nausea and vomiting while on a normal galactosecontaining diet. Eye examination disclosed multicentric, mottled, very dense cataracts bilaterally. Except for generalized clumsiFrom the Department of Pediatrics, University of Pennsylvania School of Medicine, and Children's Hospital of Philadelphia: and the Santa Rosa Children's Hospital, Santa Rosa Medical Center," and the Department of Medicine, Univers#y of Texas Health Science Center and Veteran's.7; Administration Hospital. Supported by grant HD 08536 f/om the National Institutes of Health. *Reprint address: Children's Hospital of Philadelphia, 34th St. and Civic Center Blvd., Philadelphia. PA 19104.
ness, general physi(al and neurologic examinations were unremarkable. There was no hepatomegaly. He communicated by pointing and gesture. He required help in all activities of daily living. Psychologic testing at age 8 years showed few scorable responses even at the 2-year level. A Stanford-Binet test at age 11 years, 2 months, showed a mental age of 3 years, 8 months. Blood chemistry values were normal except for a blood galactose concentration of 95 mg/dl. Results of liver function tests were normal. Quantitative ion exchange amino acid chromatography of urine and plasma revealed no abnormality. No abnormal organic acids were present in the urine. Patient 2. The brother had a normal pre- and postnatal course. He sat at 6 to 7 months and walked at 16 months. At 8 years of age he was unable to dress or feed himself, had no speech, and was not toilet-trained. Bilateral cataracts were first noted at 3% years. He has had several operations for cataracts on both eyes with visual acuity now 20/50 in both eyes. Hearing has been normal. At age 6 ye~'~s he had a brief grand mal seizure; an electroencephalogram showed spike discharges from the right hemisphere. He has been free of seizures since receiving phenobarbital. The general and neurologic examinations have been normal except for his mental status. Vineland Social Maturity Scale at age 6 years gave a social age of 2 years. He was unable to perform any tasks on the Stanford-Binet, even at the two-year level, psychologists have indicated that the mental retardation present m both boys is independent of visual loss. Results of an urine screen using Clinitest and glucose oxidase were negative, as were results of tests for amino and organic acids. The parents have been noted by multiple observers to be solicitous of these boys' welfare and to stimulate their development adequately. An older sister, age 15, and the parents are of normal intelligence and do not have cataracts. In the Table are shown the values of red cel ! galactokinase:' and d
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0022-3476/79/110750+03500.30/0 9 1979 The C. V. Mosby Co.