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Prader-Willi Syndrome: Report of Cases
Prader-Willi syndrome: report of cases
Samuel C. Foster, DMD, Boston Delayed eruption of dentition and hypoplastic enamel form ation are among the classic charac te ristics o f the Prader-Willi syndrome. Two cases are reported.
The Prader-Willi syndrome (Prader-LabhartW illi-Fanconi syndrome) was first reported in 195 6 1; since then, approximately 70 cases o f the disease have been presented in the literature. A l though probably not rare, the syndrome has elud ed diagnosis2 in many patients. More males with the disease have been reported for no other rea son than that the syndrome is more easily diag nosed in the m ale sex.3
Physical characteristics Physical characteristics o f the syndrome include obesity, hypogenitalism, diabetes mellitus, hypo tonia, shortness o f stature, acromicria, and oligo phrenia. These characteristics appear in the pa tient in infancy or early childhood. Strabismus and blue eyes and fair hair also have been noted, along with a particular facies common to all those afflicted.1-4-8 Normal or increased head circum ference and delayed closure o f the anterior fon tanelles also have been reported.3 The males have undescended testicles and phim osis.1-3’4 634 ■ JADA, Vol. 83, September 1971
In children, eruption o f deciduous and perma nent teeth is delayed; most teeth have hypoplastic enamel. Rampant caries is also present.3-5 Lesser clinical findings include absence o f cartilage in the external ear, high palate, clinodactyly and partial syndactyly, and other bone defects.2 Newborn infants with this condition usually weigh approximately 3.0 kg2-6 and are extremely weak. Sucking and crying are almost absent to the extent that feeding may become a problem. '-4-7 Dunn has shown that histologic sections o f stri ated muscle have unusually narrow fibers.8 Behavioral development and psychomotor de velopment are retarded, as is growth.1-3 These chil dren are more emotionally than intellectually stable.2 At about 2 years o f age, they show a signifi cant weight gain. Concurrently, they m ay be af flicted with seizures,9 although electroencephalo grams and pneumoencephalograms often show no gross paroxysmal activity or structural defects.2-3 The intelligence quotients o f these children range from about 20 to 80, with 50 being a reasonable m ean.2-6-8 Endocrine disorders are a major characteristic o f this syndrome. M ales have displayed patho logic endocrine function in the excretion o f ab normal amounts o f gonadotropins and subnormal adrenal cortex activity; the latter is probably a structural or functional defect in the hypothala mus or related hypophysical structures.2-3 Diabetes mellitus, found in young teen-aged patients, signals the final development o f the dis-
Fig 2 ■ Hypoplastic enamel and rampant caries in decidu ous dentition.
combination of syndromes that conceals any sin gle identity.2
Differential diagnosis
Fig 1 ■ Five-year-old boy with typical faciesof the syndrome; note size of fingers.
ease. It has been diagnosed in almost all the re ported cases.1-3-6 Acidosis or emaciation rarely is associated with the onset of this phase.
The differential diagnosis should include two syndromes that also have some of the more salient characteristics of Prader-Willi syndrome. The Laurence-Moon-Biedle syndrome manifests polydactyly, obesity, mental retardation, and shortness of stature, and is autosomal recessive. The XXXXY syndrome, a variant of Klinefelter’s syndrome, ex hibits hypogenitalism, mental retardation, and shortness of stature.11
Discussion Etiology Etiology of the syndrome remains a question. Pregnant mothers have reported decreased fetal activity4"6; cyanosis at birth has been noted in a few patients.2 Although the genetic influence is purported to be a primary factor, the inheritance factor has not been elucidated.4 Recessive genetic traits,6-9 consangunity,9 and a 14-18 transloca tion10 have been reported in the literature. Some investigators report that there is no genetic basis for the syndrome,7 whereas others, with use of biochemical tests and blood groupings, disclose that the hypothalamus is the probable causative structure.3 Clinical, biochemical, histologic, psy chologic, and genetic elements will have to be scrutinized more closely before any single etiologic agent is found. The disease might involve a
Prader-Willi syndrome is a disease that affects both males and females. It is portrayed clinically by obesity, hypotonia, shortness of stature, hypo genitalism, acromicria, diabetes mellitus, and oligophrenia, with various bony anomalies. There has been evidence of delayed eruption of the den tition as well as hypoplastic enamel formation. Although both genetic and anatomic variations have been noted in the 70 cases reported in the literature, the etiology of the disease remains a question.
Report of two cases ■ Case No. 1: A 5-year-old white boy had been admitted to The Children’s Hospital of Foster: PRADER-WILLI SYNDROME ■ 635
Fig 3 ■ Radiograph (left)of mandibular deciduous incisor region showing extensive caries and enam el hypoplasia. Unerupted permanent central incisors can be seen. Radiograph (right) of mandibular deciduous right molars with caries and enamel hypoplasia; first permanent molar iscovered with bone.
Philadelphia when he was 20 months old for a complete examination of hypotonia. As an infant, he was considered flabby, and neither turned over nor sat up until he was 1 year old. He was lethar gic and slept all day. The 19-year-old mother had been healthy dur ing her pregnancy, although she was exposed to measles during her third month, and had been treated with a vaccine. Neither she nor her 22year-old husband had any history of familial dis ease; nor did they show traits of this syndrome. A paternal grandmother had diabetes. The moth er experienced difficult labor and, under general anesthesia, had a forceps delivery of the 2.9 kg boy. The child had a left herniorrhaphy with concommitant orchiopexy at the age of 1Vz months. At 1 year of age, he had otitis media and a fe brile convulsion. The child had a good appetite, but was troubled with frequent urination (five to eight times daily) and severe constipation. There had been no re current seizures, or upper respiratory infections. No other problems were apparent. At 5 years of age, he walked (although he had difficulty climb ing and descending stairs), used sentences, and was quite congenial. Physical examination revealed an obese male, alert and pleasant, and in no distress (Fig 1). His pulse was 100 beats per minute, respiration 32, and his temperature was 37.2 C. His height was 99.6 cm and his weight was 29.1 kg. All systems were intact and within normal limits, except for size, poor muscular development, and decreased muscle bulk. His scrotum was unusually small. 636 ■ JADA, Vol. 83, September 1971
With the exception of a maxillary right decidu ous central incisor that had been extracted, all his deciduous teeth were present (Fig 2). There was also evidence on radiographs of hypoplastic enamel, as well as rampant caries (Fig 3). Biochemical tests were within normal limits, as were the blood tests for glucose and serum cholesterol. EEGs revealed an abnormal tracing, with several paroxysms of hypersynchronous slow activity mixed with spikes, suggesting a lowered potential for seizures, especially during sleep. Re sults of a right quadriceps muscle biopsy were negative for vacuolation, degeneration, and leu kocytic infiltration; diagnosis was that of normal striated muscle. Examination of a buccal smear provided no insight into chromosomal abnor mality. Radiographs of the dentition revealed caries and deficient enamel formation. The child currently is undergoing a multidisci plinary follow-up. ■ Case No. 2: A IV2 -year-old white girl was first seen by me at the special patient clinic, Uni versity of Pennsylvania School of Dental Medi cine, for routine dental procedures. Diagnosis of Prader-Willi syndrome had been made elsewhere. Past medical history revealed that the child was a month premature; her birth weight was 2.2 kg. Because of umbilical strangulation, the baby was cyanotic on delivery. She was in an incubator for two weeks and in a nursery for another four weeks. At age 9 months, she had pneumonia. When she was IV2 years old, Prader-Willi syndrome was diagnosed from clinical symptoms of hypotonia, obesity, hypogenitalism, and oligophrenia. She
Fig 6 ■ Fiadiograph of permanent m axillarycentral incisors with hypoplastic enamel. These teeth were not clinica lly evi dent.
Fig 4 ■ A 7V2-year-old girl affected with Prader-Willi syn drome. Dark brown hair and brown eyes depart from the typ i cal fair hair and blue eyes characteristic of the syndrome.
Fig 7 ■ Radiograph of mandibular right molar region show ing hypoplastic enamel and caries, especially in the first per manent molar.
Fig 5 ■ Mandibular permanent central incisors with hypo plastic enamel on labial surfaces; note delayed eruption of maxillary central incisors.
was treated at that time for bilateral club foot. The 37-year-old mother had an uneventful de livery of the child. The parents were not considered fat, although the father, who was 45 years old and 5 ft 11 inches tall, weighed 240 lb. Two siblings, a 23-year-old brother, 6 ft, 230 lb, and a 14-year-old sister, 5 ft 8 inches, 175 lb, would be considered overweight. Neither the immediate family nor distant relatives showed an uncommon medical history.
Medical history was normal except for moder ate retardation that necessitated special schooling. Physical examination revealed an obese IV2 year-old white girl (Fig 4) in no distress. Her pulse was 110 beats per minute, respiration 29, and temperature 37.0 C. Her height was 114.1 cm and weight was 42.3 kg. She had locomotive diffi culties, primarily in climbing stairs. Other systems were intact and in normal limits. She had to uri nate frequently. Laboratory tests were in normal limits. Results of blood tests, including those for glucose and serum cholesterol, biochemical and EEG findings, buccal smears, and a muscle biopsy were negative. Radiographs of the dentition and clinical find ings showed classic symptoms. Her pattern of den tition eruption was delayed about a year. Hypo plastic enamel was present in the permanent teeth (Fig 5). Radiographic examination revealed that the unerupted maxillary central incisor had hypo Foster: PRADER-WILLI SYNDROME ■ 637
plastic enamel as did the erupted mandibular cen tral incisors (Fig 6). Caries was evident in the hypoplastic regions on the permanent teeth (Fig
7). Discussion The two cases o f Prader-Willi syndrome exhibit classic medical and dental symptoms o f the dis ease. The children are short and obese, exhibit hypogenitalism, acromicria, and oligophrenia. At this time, there is no evidence o f diabetes, usual ly apparent in the early teen years, or hyperlip emia, a condition reported in some o f the litera ture. Both patients exhibit hypoplastic enamel. The boy had rampant caries, whereas the girl dis played delayed eruption with moderate caries in hypoplastic enamel regions. Follow-up medical and dental care is indicated for this syndrome.
The author is grateful to Mrs. Lillian Bryant, librarian, C hil dren’s Hospital of Philadelphia, for her aid in the preparation of th is paper. Doctor Foster is with the department of postgraduate o rth odontics, Tufts University School of Dental Medicine. His address is 136 Harrison Ave, Boston, 02111. This paper was
638 ■ JADA, Vol. 83, September 1971
prepared while he was in residency at The Children’s Hospital of Philadelphia. 1. Prader, A.; Labhart, A.; and Willi, H. Ein Syndrom von Adipositas, Kleinwuchs, Kryptorchismus und Oligophrenie nach Myatonieartigen Zustand im Neugemborenenalter. Schweiz Med Wschr 86:1260 Jan 1956. 2. Forssman, H., and Hagberg, B. Prader-Willi syndrome in boy o f ten with prediabetes. Acta Paediat 53:70 Jan 1964. 3. Dunn, H.G. The Prader-Labhart-Willi syndrome: review of the literature and report of nine cases. Acta Paediat Scand Suppl 186, 1968, c it no. 4124716. 4. Prader, A., and others. Ein Syndrom von Adipositas, Kleinwuchs, Kryptorchismus und Idiotie bie Kindern und Erwachsenen, die als Neugeborene ein Myatonie—artiges Bild Geboten Haben. Proc 8th Internati Cong Paediatrics, Copenhagen, 1956. 5. Hooft, C.; Deline, C.; and Casneuf, J. Le Syndrome de Prader-Labhardt-Willi-Fanconi. Acta Paediat Belg 20:27 April 1966. 6. Prader, A., and Willi, H. Das Syndrom von Imbezillität, Adipositas, Muskelhypotonie, Hypogenitalism us, Hypogonad ismus und Diabetes Mellitus m it “ Myotonie” . Proc 2nd Inter nati Cong Mental Retardation, Vienna, 1961. Part I, Basel and New York, S. Karger, 1963, p 353. 7. McKusick, V.A. Mendelian inheritance in man, ed 2. Catalogue no. 1646, Prader-Willi Syndrome. Baltimore, Johns Hopkins Press, 1968, p 178. 8. Dunn, H.G., and Miller, J.R. Benign hypotonia with hypogenitalism. Read at 73rd annual meeting, American Pe diatric Society, Atlantic City, Abstracted, no. 42, J Pediat 63: 873 Sept 1963. 9. Royer, P. Le Diabète sucré dans le syndrome de W illiPrader. Journées Ann Diabet, HStel Dieu 4:91, 1963. 10. Zellweger, H., and Mikamo, K. Autosomal cytogenetics. Helv Paediat Acta 16:670 Dec 1961. 11. Nelson, W.E., and others. Textbook of pediatrics, ed 9. Philadelphia, W. B. Saunders Co., 1969, p 1525.
Samuel C. Foster, DMD, Boston Delayed eruption of dentition and hypoplastic enamel form ation are among the classic charac te ristics o f the Prader-Willi syndrome. Two cases are reported.
The Prader-Willi syndrome (Prader-LabhartW illi-Fanconi syndrome) was first reported in 195 6 1; since then, approximately 70 cases o f the disease have been presented in the literature. A l though probably not rare, the syndrome has elud ed diagnosis2 in many patients. More males with the disease have been reported for no other rea son than that the syndrome is more easily diag nosed in the m ale sex.3
Physical characteristics Physical characteristics o f the syndrome include obesity, hypogenitalism, diabetes mellitus, hypo tonia, shortness o f stature, acromicria, and oligo phrenia. These characteristics appear in the pa tient in infancy or early childhood. Strabismus and blue eyes and fair hair also have been noted, along with a particular facies common to all those afflicted.1-4-8 Normal or increased head circum ference and delayed closure o f the anterior fon tanelles also have been reported.3 The males have undescended testicles and phim osis.1-3’4 634 ■ JADA, Vol. 83, September 1971
In children, eruption o f deciduous and perma nent teeth is delayed; most teeth have hypoplastic enamel. Rampant caries is also present.3-5 Lesser clinical findings include absence o f cartilage in the external ear, high palate, clinodactyly and partial syndactyly, and other bone defects.2 Newborn infants with this condition usually weigh approximately 3.0 kg2-6 and are extremely weak. Sucking and crying are almost absent to the extent that feeding may become a problem. '-4-7 Dunn has shown that histologic sections o f stri ated muscle have unusually narrow fibers.8 Behavioral development and psychomotor de velopment are retarded, as is growth.1-3 These chil dren are more emotionally than intellectually stable.2 At about 2 years o f age, they show a signifi cant weight gain. Concurrently, they m ay be af flicted with seizures,9 although electroencephalo grams and pneumoencephalograms often show no gross paroxysmal activity or structural defects.2-3 The intelligence quotients o f these children range from about 20 to 80, with 50 being a reasonable m ean.2-6-8 Endocrine disorders are a major characteristic o f this syndrome. M ales have displayed patho logic endocrine function in the excretion o f ab normal amounts o f gonadotropins and subnormal adrenal cortex activity; the latter is probably a structural or functional defect in the hypothala mus or related hypophysical structures.2-3 Diabetes mellitus, found in young teen-aged patients, signals the final development o f the dis-
Fig 2 ■ Hypoplastic enamel and rampant caries in decidu ous dentition.
combination of syndromes that conceals any sin gle identity.2
Differential diagnosis
Fig 1 ■ Five-year-old boy with typical faciesof the syndrome; note size of fingers.
ease. It has been diagnosed in almost all the re ported cases.1-3-6 Acidosis or emaciation rarely is associated with the onset of this phase.
The differential diagnosis should include two syndromes that also have some of the more salient characteristics of Prader-Willi syndrome. The Laurence-Moon-Biedle syndrome manifests polydactyly, obesity, mental retardation, and shortness of stature, and is autosomal recessive. The XXXXY syndrome, a variant of Klinefelter’s syndrome, ex hibits hypogenitalism, mental retardation, and shortness of stature.11
Discussion Etiology Etiology of the syndrome remains a question. Pregnant mothers have reported decreased fetal activity4"6; cyanosis at birth has been noted in a few patients.2 Although the genetic influence is purported to be a primary factor, the inheritance factor has not been elucidated.4 Recessive genetic traits,6-9 consangunity,9 and a 14-18 transloca tion10 have been reported in the literature. Some investigators report that there is no genetic basis for the syndrome,7 whereas others, with use of biochemical tests and blood groupings, disclose that the hypothalamus is the probable causative structure.3 Clinical, biochemical, histologic, psy chologic, and genetic elements will have to be scrutinized more closely before any single etiologic agent is found. The disease might involve a
Prader-Willi syndrome is a disease that affects both males and females. It is portrayed clinically by obesity, hypotonia, shortness of stature, hypo genitalism, acromicria, diabetes mellitus, and oligophrenia, with various bony anomalies. There has been evidence of delayed eruption of the den tition as well as hypoplastic enamel formation. Although both genetic and anatomic variations have been noted in the 70 cases reported in the literature, the etiology of the disease remains a question.
Report of two cases ■ Case No. 1: A 5-year-old white boy had been admitted to The Children’s Hospital of Foster: PRADER-WILLI SYNDROME ■ 635
Fig 3 ■ Radiograph (left)of mandibular deciduous incisor region showing extensive caries and enam el hypoplasia. Unerupted permanent central incisors can be seen. Radiograph (right) of mandibular deciduous right molars with caries and enamel hypoplasia; first permanent molar iscovered with bone.
Philadelphia when he was 20 months old for a complete examination of hypotonia. As an infant, he was considered flabby, and neither turned over nor sat up until he was 1 year old. He was lethar gic and slept all day. The 19-year-old mother had been healthy dur ing her pregnancy, although she was exposed to measles during her third month, and had been treated with a vaccine. Neither she nor her 22year-old husband had any history of familial dis ease; nor did they show traits of this syndrome. A paternal grandmother had diabetes. The moth er experienced difficult labor and, under general anesthesia, had a forceps delivery of the 2.9 kg boy. The child had a left herniorrhaphy with concommitant orchiopexy at the age of 1Vz months. At 1 year of age, he had otitis media and a fe brile convulsion. The child had a good appetite, but was troubled with frequent urination (five to eight times daily) and severe constipation. There had been no re current seizures, or upper respiratory infections. No other problems were apparent. At 5 years of age, he walked (although he had difficulty climb ing and descending stairs), used sentences, and was quite congenial. Physical examination revealed an obese male, alert and pleasant, and in no distress (Fig 1). His pulse was 100 beats per minute, respiration 32, and his temperature was 37.2 C. His height was 99.6 cm and his weight was 29.1 kg. All systems were intact and within normal limits, except for size, poor muscular development, and decreased muscle bulk. His scrotum was unusually small. 636 ■ JADA, Vol. 83, September 1971
With the exception of a maxillary right decidu ous central incisor that had been extracted, all his deciduous teeth were present (Fig 2). There was also evidence on radiographs of hypoplastic enamel, as well as rampant caries (Fig 3). Biochemical tests were within normal limits, as were the blood tests for glucose and serum cholesterol. EEGs revealed an abnormal tracing, with several paroxysms of hypersynchronous slow activity mixed with spikes, suggesting a lowered potential for seizures, especially during sleep. Re sults of a right quadriceps muscle biopsy were negative for vacuolation, degeneration, and leu kocytic infiltration; diagnosis was that of normal striated muscle. Examination of a buccal smear provided no insight into chromosomal abnor mality. Radiographs of the dentition revealed caries and deficient enamel formation. The child currently is undergoing a multidisci plinary follow-up. ■ Case No. 2: A IV2 -year-old white girl was first seen by me at the special patient clinic, Uni versity of Pennsylvania School of Dental Medi cine, for routine dental procedures. Diagnosis of Prader-Willi syndrome had been made elsewhere. Past medical history revealed that the child was a month premature; her birth weight was 2.2 kg. Because of umbilical strangulation, the baby was cyanotic on delivery. She was in an incubator for two weeks and in a nursery for another four weeks. At age 9 months, she had pneumonia. When she was IV2 years old, Prader-Willi syndrome was diagnosed from clinical symptoms of hypotonia, obesity, hypogenitalism, and oligophrenia. She
Fig 6 ■ Fiadiograph of permanent m axillarycentral incisors with hypoplastic enamel. These teeth were not clinica lly evi dent.
Fig 4 ■ A 7V2-year-old girl affected with Prader-Willi syn drome. Dark brown hair and brown eyes depart from the typ i cal fair hair and blue eyes characteristic of the syndrome.
Fig 7 ■ Radiograph of mandibular right molar region show ing hypoplastic enamel and caries, especially in the first per manent molar.
Fig 5 ■ Mandibular permanent central incisors with hypo plastic enamel on labial surfaces; note delayed eruption of maxillary central incisors.
was treated at that time for bilateral club foot. The 37-year-old mother had an uneventful de livery of the child. The parents were not considered fat, although the father, who was 45 years old and 5 ft 11 inches tall, weighed 240 lb. Two siblings, a 23-year-old brother, 6 ft, 230 lb, and a 14-year-old sister, 5 ft 8 inches, 175 lb, would be considered overweight. Neither the immediate family nor distant relatives showed an uncommon medical history.
Medical history was normal except for moder ate retardation that necessitated special schooling. Physical examination revealed an obese IV2 year-old white girl (Fig 4) in no distress. Her pulse was 110 beats per minute, respiration 29, and temperature 37.0 C. Her height was 114.1 cm and weight was 42.3 kg. She had locomotive diffi culties, primarily in climbing stairs. Other systems were intact and in normal limits. She had to uri nate frequently. Laboratory tests were in normal limits. Results of blood tests, including those for glucose and serum cholesterol, biochemical and EEG findings, buccal smears, and a muscle biopsy were negative. Radiographs of the dentition and clinical find ings showed classic symptoms. Her pattern of den tition eruption was delayed about a year. Hypo plastic enamel was present in the permanent teeth (Fig 5). Radiographic examination revealed that the unerupted maxillary central incisor had hypo Foster: PRADER-WILLI SYNDROME ■ 637
plastic enamel as did the erupted mandibular cen tral incisors (Fig 6). Caries was evident in the hypoplastic regions on the permanent teeth (Fig
7). Discussion The two cases o f Prader-Willi syndrome exhibit classic medical and dental symptoms o f the dis ease. The children are short and obese, exhibit hypogenitalism, acromicria, and oligophrenia. At this time, there is no evidence o f diabetes, usual ly apparent in the early teen years, or hyperlip emia, a condition reported in some o f the litera ture. Both patients exhibit hypoplastic enamel. The boy had rampant caries, whereas the girl dis played delayed eruption with moderate caries in hypoplastic enamel regions. Follow-up medical and dental care is indicated for this syndrome.
The author is grateful to Mrs. Lillian Bryant, librarian, C hil dren’s Hospital of Philadelphia, for her aid in the preparation of th is paper. Doctor Foster is with the department of postgraduate o rth odontics, Tufts University School of Dental Medicine. His address is 136 Harrison Ave, Boston, 02111. This paper was
638 ■ JADA, Vol. 83, September 1971
prepared while he was in residency at The Children’s Hospital of Philadelphia. 1. Prader, A.; Labhart, A.; and Willi, H. Ein Syndrom von Adipositas, Kleinwuchs, Kryptorchismus und Oligophrenie nach Myatonieartigen Zustand im Neugemborenenalter. Schweiz Med Wschr 86:1260 Jan 1956. 2. Forssman, H., and Hagberg, B. Prader-Willi syndrome in boy o f ten with prediabetes. Acta Paediat 53:70 Jan 1964. 3. Dunn, H.G. The Prader-Labhart-Willi syndrome: review of the literature and report of nine cases. Acta Paediat Scand Suppl 186, 1968, c it no. 4124716. 4. Prader, A., and others. Ein Syndrom von Adipositas, Kleinwuchs, Kryptorchismus und Idiotie bie Kindern und Erwachsenen, die als Neugeborene ein Myatonie—artiges Bild Geboten Haben. Proc 8th Internati Cong Paediatrics, Copenhagen, 1956. 5. Hooft, C.; Deline, C.; and Casneuf, J. Le Syndrome de Prader-Labhardt-Willi-Fanconi. Acta Paediat Belg 20:27 April 1966. 6. Prader, A., and Willi, H. Das Syndrom von Imbezillität, Adipositas, Muskelhypotonie, Hypogenitalism us, Hypogonad ismus und Diabetes Mellitus m it “ Myotonie” . Proc 2nd Inter nati Cong Mental Retardation, Vienna, 1961. Part I, Basel and New York, S. Karger, 1963, p 353. 7. McKusick, V.A. Mendelian inheritance in man, ed 2. Catalogue no. 1646, Prader-Willi Syndrome. Baltimore, Johns Hopkins Press, 1968, p 178. 8. Dunn, H.G., and Miller, J.R. Benign hypotonia with hypogenitalism. Read at 73rd annual meeting, American Pe diatric Society, Atlantic City, Abstracted, no. 42, J Pediat 63: 873 Sept 1963. 9. Royer, P. Le Diabète sucré dans le syndrome de W illiPrader. Journées Ann Diabet, HStel Dieu 4:91, 1963. 10. Zellweger, H., and Mikamo, K. Autosomal cytogenetics. Helv Paediat Acta 16:670 Dec 1961. 11. Nelson, W.E., and others. Textbook of pediatrics, ed 9. Philadelphia, W. B. Saunders Co., 1969, p 1525.