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Clinical and molecular genetics study of spinal muscular atrophy (SMA)
reflexes were hyperactive throughout. Arms and legs were constantly moving with gross tremor. Dystonic postures in the hands and legs were obvious. They did not have feeding difficulties. Laboratory studies, EEG, and CT were always normal. DHPR in both was 1.82 nM (normal). Complete remission of symptoms was obtained in 2 days on a continuous small dose of levodopa (30 rag/day). In May, 1990, treatment was stopped with a rapid return of symptoms and again disappeared when levodopa was restarted. Present age is 4 years. Motor and mental development are normal. Levodopa dose has been constant (30 mg/day). The condition of these patients suggest the probability of a very early form of Segawa disease but to our knowledge, there have been no reports of neonatal onset. Therefore, the possibility of a new, rare disease cannot be excluded.
We report the advanced study of a new syndrome characterized by the association of bilateral occipital calcifications (BOC), epilepsy, and celiac disease. Thirteen previously reported patients and 7 new ones, affected by BOC, were investigated. Nineteen of them (95%) suffered from epilepsy. In 8 of 16 cases studied (50%) intestinal biopsy revealed celiac disease. The following data emerged from our study: (1) patients with BOC present quite different clinical courses, which may vary from relatively benign partial epilepsy (14 cases) to severe epileptic encephalopathy (4 cases); (2) there is a high prevalence of celiac disease in patients with BOC; (3) clinical and neuroimaging features of BOC patients are clearly distinguishable from those with Sturge-Weber syndrome both on the clinical and neuroimaging level; and, (4) unilateral calcification may become bilateral.
104. INTERNATIONAL HEADACHE SOCIETY (IHS) CRITERIA AND CHILDHOOD HEADACHE Shashi S. Seshia, Jorg Wolstein, Coleen Adams, Frances Booth, and James Reggin, Winnipeg, Canada
106. CLINICAL AND MOLECULAR GENETICS STUDY OF SPINAL MUSCULAR ATROPHY (SMA) Michel Vanasse, MD, Solange Lebrun, IL, and Michael Strobel, PhD, Montr6al, Canada
The objective of our prospective study was to determine if the intuitive clinical diagnosis of headache made by 4 pediatric neurologists would also have fulfilled INS requirements for the diagnosis. The subjects were 58 children with recurrent headaches seen between October, 1991 and March, 1992. Clinical information was recorded on data sheets as were the clinicians' diagnoses. One author (JW) independently applied the INS criteria to the clinical information. There were 25 boys and 33 girls. Their ages ranged from 4.3-17 years (median age: 11.2 years). The history was obtained primarily from the child in 45%, from parents and child in 40% and from parents alone in 15%. The clinical diagnosis was: (1) migraine without aura (n = 41), (2) migraine with aura (n = 12), (3) tension type (n = 3), and (4) post traumatic (n = 2). The clinical diagnosis was concordant with the INS diagnosis in 43 of 58 (74%). All 15 children in whom the requirements for the IHS diagnosis were not met had migraine without aura. The following criteria/characteristics considered important by the INS for migraine without aura occurred in a relatively small number, and may have contributed to the failure to fulfill the INS requirements: (1) unilateral location (only 38%) and (2) aggravation by physical activity (only 28%), phonophobia (only 40%). Additionally, quality could not be judged in 30% and the duration was shorter than 2 hours in 13%. A family history of migraine in first- or seconddegree relatives was obtained in 77% of those with migraine. We conclude that: (1) there is good concordance between intuitive clinical diagnosis and INS diagnosis; and, (2) therefore, the INS criteria can be applied to the majority of children. However, the history may be biased by parental account. We suggest that: (1) less weight be given to unilateral location, quality and characteristics with a relatively low incidence and high subjectivity; (2) greater weight be given to vomiting and severe photophobia; and, (3) family history of migraine be included as a criterion.
Over the last 12 years, we followed 53 patients affected by chronic SMA. An evaluation including spine x-rays, manual testing of 30 muscles and respiratory function tests was done, on average, every 6 months in children and once a year in adults. Patients were divided into two groups. Group I included 41 patients who never walked without assistance and group II consisted of 22 patients who could do so. Eight patients died over the follow-up period; their ages ranged from 5-37 years and all belonged to group I. In the 55 surviving patients, statistical analysis showed a clear correlation between the duration of the disease and the three variables measured (manual muscle testing, scoliosis, and respiratory function tests). Fourteen of the 22 patients of group II have already lost ambulation at a mean age of 6.5 years (range: 1.5-17 years). They were 7 families with two affected patients each but in only 4 families did the two sibs belong to the same group. Molecular genetics studies done in these families confirmed a linkage with chromosome 5 in all cases. These data clearly show that although there may be a varying degree of clinical severity, childhood chronic SMA is a single clinical and genetic entity which is clearly progressive in the vast majority of patients.
105. SYNDROME OF BILATERAL OCCIPITAL CALCIFICATIONS, EPILEPSY, AND CELIAC DISEASE: REPORT OF 20 CASES Adriana Magaudda, Bernardo Della Bernardina, Vito Colamaria, Pasquale De Marco, Zen6n M. Sfaello, Ornella Daniele, Gaetano Tortorella, and Mario Meduri, Messina, Italy
107. FOLLOW-UP OF EARLY DIAGNOSED PHENYLKETONURIC PATIENTS IN CHILE Ver6nica Cornejo, Erna Raimann, Carmen G. Perales, and Marta Colombo, Santiago, Chile Phenylketonuria (PKU) is the most frequent inborn error of metabolism. The average incidence is 1:10,000 newborns. In 1988, a newborn screening program for PKU was started in the central area of Santiago, Chile, covering 25% of the newborn population of the city. We present 7 patients with classic PKU, 6 of whom were diagnosed through this program and the other is a sibling of a late diagnosed PKU patient. Their average age is 24 months (range: 2-72 months). All of them had phenylalanine (Phe) plasma levels > 20 mg/dl in the first blood sample. The diagnosis was confirmed by quantitative amino acid assay by HPLC (X Phe level 32 mg/dl). They began the Phe-restricted diet at average age of 17.5 days of life (10-28 days). The Phe intake is 180-250 mg/day. The follow-up includes medical, bio-
PEDIATRIC NEUROLOGY Vol.8 No. 5 371
We report the advanced study of a new syndrome characterized by the association of bilateral occipital calcifications (BOC), epilepsy, and celiac disease. Thirteen previously reported patients and 7 new ones, affected by BOC, were investigated. Nineteen of them (95%) suffered from epilepsy. In 8 of 16 cases studied (50%) intestinal biopsy revealed celiac disease. The following data emerged from our study: (1) patients with BOC present quite different clinical courses, which may vary from relatively benign partial epilepsy (14 cases) to severe epileptic encephalopathy (4 cases); (2) there is a high prevalence of celiac disease in patients with BOC; (3) clinical and neuroimaging features of BOC patients are clearly distinguishable from those with Sturge-Weber syndrome both on the clinical and neuroimaging level; and, (4) unilateral calcification may become bilateral.
104. INTERNATIONAL HEADACHE SOCIETY (IHS) CRITERIA AND CHILDHOOD HEADACHE Shashi S. Seshia, Jorg Wolstein, Coleen Adams, Frances Booth, and James Reggin, Winnipeg, Canada
106. CLINICAL AND MOLECULAR GENETICS STUDY OF SPINAL MUSCULAR ATROPHY (SMA) Michel Vanasse, MD, Solange Lebrun, IL, and Michael Strobel, PhD, Montr6al, Canada
The objective of our prospective study was to determine if the intuitive clinical diagnosis of headache made by 4 pediatric neurologists would also have fulfilled INS requirements for the diagnosis. The subjects were 58 children with recurrent headaches seen between October, 1991 and March, 1992. Clinical information was recorded on data sheets as were the clinicians' diagnoses. One author (JW) independently applied the INS criteria to the clinical information. There were 25 boys and 33 girls. Their ages ranged from 4.3-17 years (median age: 11.2 years). The history was obtained primarily from the child in 45%, from parents and child in 40% and from parents alone in 15%. The clinical diagnosis was: (1) migraine without aura (n = 41), (2) migraine with aura (n = 12), (3) tension type (n = 3), and (4) post traumatic (n = 2). The clinical diagnosis was concordant with the INS diagnosis in 43 of 58 (74%). All 15 children in whom the requirements for the IHS diagnosis were not met had migraine without aura. The following criteria/characteristics considered important by the INS for migraine without aura occurred in a relatively small number, and may have contributed to the failure to fulfill the INS requirements: (1) unilateral location (only 38%) and (2) aggravation by physical activity (only 28%), phonophobia (only 40%). Additionally, quality could not be judged in 30% and the duration was shorter than 2 hours in 13%. A family history of migraine in first- or seconddegree relatives was obtained in 77% of those with migraine. We conclude that: (1) there is good concordance between intuitive clinical diagnosis and INS diagnosis; and, (2) therefore, the INS criteria can be applied to the majority of children. However, the history may be biased by parental account. We suggest that: (1) less weight be given to unilateral location, quality and characteristics with a relatively low incidence and high subjectivity; (2) greater weight be given to vomiting and severe photophobia; and, (3) family history of migraine be included as a criterion.
Over the last 12 years, we followed 53 patients affected by chronic SMA. An evaluation including spine x-rays, manual testing of 30 muscles and respiratory function tests was done, on average, every 6 months in children and once a year in adults. Patients were divided into two groups. Group I included 41 patients who never walked without assistance and group II consisted of 22 patients who could do so. Eight patients died over the follow-up period; their ages ranged from 5-37 years and all belonged to group I. In the 55 surviving patients, statistical analysis showed a clear correlation between the duration of the disease and the three variables measured (manual muscle testing, scoliosis, and respiratory function tests). Fourteen of the 22 patients of group II have already lost ambulation at a mean age of 6.5 years (range: 1.5-17 years). They were 7 families with two affected patients each but in only 4 families did the two sibs belong to the same group. Molecular genetics studies done in these families confirmed a linkage with chromosome 5 in all cases. These data clearly show that although there may be a varying degree of clinical severity, childhood chronic SMA is a single clinical and genetic entity which is clearly progressive in the vast majority of patients.
105. SYNDROME OF BILATERAL OCCIPITAL CALCIFICATIONS, EPILEPSY, AND CELIAC DISEASE: REPORT OF 20 CASES Adriana Magaudda, Bernardo Della Bernardina, Vito Colamaria, Pasquale De Marco, Zen6n M. Sfaello, Ornella Daniele, Gaetano Tortorella, and Mario Meduri, Messina, Italy
107. FOLLOW-UP OF EARLY DIAGNOSED PHENYLKETONURIC PATIENTS IN CHILE Ver6nica Cornejo, Erna Raimann, Carmen G. Perales, and Marta Colombo, Santiago, Chile Phenylketonuria (PKU) is the most frequent inborn error of metabolism. The average incidence is 1:10,000 newborns. In 1988, a newborn screening program for PKU was started in the central area of Santiago, Chile, covering 25% of the newborn population of the city. We present 7 patients with classic PKU, 6 of whom were diagnosed through this program and the other is a sibling of a late diagnosed PKU patient. Their average age is 24 months (range: 2-72 months). All of them had phenylalanine (Phe) plasma levels > 20 mg/dl in the first blood sample. The diagnosis was confirmed by quantitative amino acid assay by HPLC (X Phe level 32 mg/dl). They began the Phe-restricted diet at average age of 17.5 days of life (10-28 days). The Phe intake is 180-250 mg/day. The follow-up includes medical, bio-
PEDIATRIC NEUROLOGY Vol.8 No. 5 371