DIAGNOSIS and TREATMENT
Robert A. Boraz, DDS
Cri-du-chat syndrome: dental considerations and report of case
Cri-du-chat syndrome is a severe disease resulting from a deletion of the short arm of chromosome number 5. The basic medical disorder includes dysmorphic facies, mental retardation, and a striking catlike cry in infancy. Because of significant oral anomalies and difficulty in behavior management, the syndrome is of particular interest to the dental practitioner. A case with many of the typical medical findings and significant dental considerations is reported. An aggressive preventive dentistry program is essential. A thorough understanding of the medical and developmental problems of the patient with cri-duchat syndrome ensures safe and effective dental care.
C
ri-du-chat syndrome (46,XY, 5p-) was first described by Lejeune in 1963.’ In the literature, three females with dysmorphic facies, mental retardation, and a striking catlike cry during infancy were described.’ In all three patients, a deletion of the short arm of a B group chromosome was demonstrated and identified subsequently by autoradiography as number 5 . 2 yMany experts used to consider all autosomal chromosome deletions lethal. Partial deletions of autosomal chromosomes carry a varied prognosis. The overall outlook for quality and length of life has improved greatly for these patients and is thus of significance to dentists.’*The underlying chromosomal aberration has appeared as a new phenomenon in the majority of cases.’ I ’ I 3 Approximately 100 cases of cri-du-chat syndrome have been identified.’
Review of the literature The classic abnormalities associated with cri-du-chat syndrome include low birth weight (less than 2.5 kg), slow growth, catlike cry, mental retardation, hypotonia, microcephaly , facial asymmetry, micrognathia, dental malocclusion, hypertelorism, epicanthal folds, downward slanting palpebral fissures, and congenital heart disease. Other findings in these patients may include cleft lip and palate, myopia, preauricular skin tags, bifid uvula, and an absent kidney or spleen. 2.5.6.12.14.15 Originally, these patients were thought to be profoundly mentally retarded with intelligence quotients in the range of 20 to 30.’ Recent observations have indicated that many children with cri-du-chat syndrome can attain social and developmental skills in the mild to moderate retardation range. Optimal results have been obtained with early infant and childhood training pro-
grams. Linguistic abilities have been the most difficult to influence in a favorable fashion.I3The intelligence of individuals is negatively correlated with the size of the 5p- deletion.I3 The catlike cry associated with cri-duchat syndrome is ascribed to abnormal laryngeal development.2,8Laryngeal webs, presumably remnants of the tissue that temporarily occludes the embryonic larynx, are almost anterior to the vocal cords. The larynx is narrow, and the epiglottis is flaccid, so that it falls back to obstruct the laryngeal inlet and causes stridor. I6 During phonation and crying, the voice is further weakened by air leakage because of failure of the vocal cords to approximate posteriorly and the highpitched mewing cry results from the approximated anterior portion of the vocal cords. As patients get older, the catlike cry is less noticeable and may complicate the late diagnosis of these patients.* Special Care in Dentistry, January-February 1990 13
With a high incidence of congenital heart disease, chronic respiratory infections from aspiration, and mental retardation, dental management of patients with cri-du-chat syndrome can be challenging. As with any patient with mental retardation, obtaining adequate patient management necessary for rendering safe and successful dental treatment may be difficult or impossible. If congenital heart disease is also present, appropriate antibiotic prophylaxis is essential. If general anesthesia is deemed necessary to manage the patient, additional anesthetic risks may result from the congenital heart disease. Retrognathia and a high, vaulted palate may increase the complexity of intubation. Because many infants are hypotonic, the response to muscle relaxants may be accentuated and unpredictable. This places emphasis on giving small doses and monitoring neurornuscular function to avoid the complications associated with respiratory distress. The main anesthetic concerns center around abnormalities in the larynx and upper airway. However, if appropriate care and precautions are taken, general anesthesia can usually be accomplished safely and effectively. ” The cause of cri-du-chat syndrome is the partial deletion of the short arm of chromosome number 5.’ This finding has appeared as a fresh entity in the majority of cases. Two possibilities may explain this genetically: mosaicism and translocation. Support for the theory of translocation comes from the observation that in 10%to 15%of the cases, a balanced translocation in one parent has been identified. These individuals carry an increased risk of occurrence of the syndrome. No similar support for the theory of mosaicism has been identified.’ Report of case
The male patient was born at the University of Kansas Medical Center in 1980. The mother, a 23-year-old female, had delivered a full-term, normal male child 4 1/2 years previously. The first child weighed approximately 7 Ibs. The family history was unremarkable. The mother then took oral contraceptives for 3 years and practiced no birth control for approximately 8 months before conception. She denied any infections, vaginal bleeding, or injuries during pregnancy. Calcium pills and vitamins were the only medications she 14 Special Care in Dentistry, January-February 1990
Fig 1. Facial view of patient. took. While pregnant, the mother indicated she smoked approximately one pack of cigarettes per week and she denied the use of alcoholic beverages. The pregnancy was uncomplicated until the mother noted maternal weight loss in the seventh month and a decided decrease in fetal movement. Two oxytocin challenge tests each demonstrated fetal distress. A sonogram also showed intrauterine growth retardation. The patient was delivered by cesarean section and weighed 1,760 g. He immediately developed respiratory stress syndrome and was placed on positive pressure oxygen via a ventilator. He remained hospitalized in a neonatal intensive care facility for approximately 4 weeks. The patient was hospitalized several times in the next 2 1/2 years, primarily for evaluation of developmental delays and failure to thrive. He did not even start to crawl until 22 months of age. Neurologic evaluation showed a severe developmental delay. He also demonstrated a severe hearing loss of the right ear and a slight loss of the left ear. Chromosome analysis revealed the patient had cri-du-chat syndrome (46,XY, 5p-) with the deletion being of a very significant size. The patient was first examined in the dental clinic at the University of Kansas Medical Center shortly after the diagnosis of his syndrome. Physical evaluation showed severe mental and growth retardation (Fig 1). He demonstrated microcephaly, a bifid uvula, and relative micrognathia (Fig 2). Epicanthal folds were present as well as unusual creases in the fifth fingers. The typical catlike cry associated with cri-du-chat syndrome was apparent. Visual and radiographic evaluation showed several dental carious lesions. An anterior open bite and a high, narrow, vaulted palate were
visible (Fig 3). Because of the recent diagnosis of the anomaly and the questionable ability of the patient to cooperate, the parents deferred treatment at that time. They also refused to consider the alternative of general anesthesia although no congenital heart defect was present. The patient returned for reexamination approximately 1 year later. Several new carious lesions were apparent. Amalgam, composite, and stainless steel crown restorations were safely and effectively provided. A papoose restraint board and chloral hydrate sedation (50 mg/kg) for patient management were used at each of two visits in addition to local anesthesia with 2 % mepivacaine hydrochloride with levonordefrin 1:20,OOO. The patient was alert and awake throughout treatment and cooper-
Fig 2. Patient profile view showing retrognathia.
Fig 3. View of anterior occlusion depicting anterior open bite.
ated at an acceptable level. The patient was carefully and appropriately monitored throughout the procedures. The parents had selected this mode of management over the use of general anesthesia. A thorough preventive dental program was designed and instituted for the patient. This program included the mother’s receiving instruction and demonstrating proficiency with the modified Stillman toothbrushing technique. Instructions included the mother’s brushing the patient’s teeth with a soft bristle toothbrush and use of a fluoride dentifrice twice daily after breakfast and before bedtime. The patient was unable to accomplish this task as demonstrated by the rate of dental caries and an inadequate plaque index. Dental flossing was taught to the patient’s mother with instruction to be performed daily. Home fluoride therapy was desirable but deemed inappropriate as the patient was not able to rinse and expectorate. Nutrition theory and practical recommendations were discussed in depth with an emphasis placed on decreased frequency of sugar intake. A recommendation for recall examinations at least every 3 months was instituted. With the patient being a difficult management problem, the parents were advised of the essential nature of compliance with the preventive program. Three years elapsed before the patient was seen in the dental clinic again as the family had moved away a significant distance. The patient was 8 1/2 years of age and was undergoing an orthodontic and orthopedic evaluation by another practitioner. His records indicated moderate to severe dental crowding of the maxillary and mandibular arches and an Angle Class II skeletal malocclusion as a result of mandibular retrognathia. A large dental overjet had developed. The orthodontist planned to use functional appliances to begin correcting the patient’s dental crowding and retrognathia.
The mother of the patient requested a second opinion on the recommended orthodontic and orthopedic treatment. Review of the records and evaluation of the patient indicated the treatment proposed was appropriate for a compliant patient. However, the patient demonstrated no significant improvement in his ability to cooperate and the mother and practitioner agreed that the treatment prognosis would be highly questionable. The mother decided to proceed with the treatment anyway. Visual examination at the time of the consultation showed a significant improvement in oral hygiene. No new restorations were visually apparent and no new dental problems were noted. The patient did not return for further evaluation nor was information available on the success of the orthodontic treatment. Conclusion
The case of a patient with cri-du-chat syndrome is presented. Oral anomalies that develop in these patients can be difficult to manage because of the associated medical and developmental problems. An aggressive preventive dentistry program is indicated. Behavior management of these patients is usually difficult, as is frequently the case with medically and mentally compromised patients. A thorough understanding of the medical problems of the patient with cri-du-chat syndrome can allow for the safe and effective delivery of dental care that is essential for the attainment of the maximum level of quality of life possible.
Dr. Boraz is associate professor of surgery and pediatrics and director, dental service, University of Kansas Medical Center, 39th and Rainbow Blvd, Kansas City, KS 66103. Address requests for reprints to Dr. Boraz.
I . Lejeune J, Lafouracade 1, Berger, R, et al. Trois cas de deletion partielle du bras court du chromosome 5 . CR Acad Sci [D] (Paris)
1963;257:3098-102. 2. Jones KL. Smith’s recognizable patterns of human malformation. Philadelphia: Saunders, I988:40- I . 3. Wilkins LE, Brown, JA. Nance, WE, et al. Clinical heterogeneity in 80 home reared children with cri-du-chat syndrome. J Pediatr 1983; 102528-33. 4. Berg JM, Delhanty JDA, Faunch JA, et al. Partial deletion of short arm of a chromosome of the 4 and S group (Denver) in an adult male. J Ment Defic Res 1965;9:219-28. 5 . Breg WR, Steele MW, Miller 01, et al. The cri-du-chat syndrome in adolescents and adults: clinical findings in 13 older patients with partial deletion of the short arm of chromosome no. S (5p-). I Pediatr 1970;77:782-91. 6. Sucheston ME, Cannon MS. Congenital malformations. Philadelphia: FA Davis Co, 1973: 15-7. 7. German 1, Lejeune J, Macentyre MN, et al. Chromosomal autoradiography in cri-du-chat syndrome. Cytogenetics I964;3:347-52. 8. Macintyre MN. Stiples WT, La Polla JJ, el al. “The cat cry” syndrome. Am J Dis Child 1964; 108538.42. 9. Wilkins LE, Brown JA, Wolf B. Psychomotor development in 6.5 home-reared children with cri-du-chat syndrome. J Pediatr 1980;97:4O1-5. 10. Behram RE, Vaughan VC. Nelson Textbook of Pediatrics. Philadelphia: Saunders, 1983:302-3. 1 1 , Miller OJ, Breg WR, Warburton D, el al. Partial deletion of the short arm chromosome no. 4 (4p.): clinical studies in five unrelated patients. J Pediatr 1970;77:792-801. 12. Bergsma D, McKusick VA, Ozer FL, et al. The fifth conference on the clinical delineation of birth defects. Part XVI, urinary system and others. Baltimore: Williams and Wilkins , 1974:349-50. 13. Kushnick T, Rao KW, Lamb AN. Familial Sp-syndrome. Clin Genet 1984;26:472-6. 14. Fenger K, Niebuhr E. Discriminant analysis of dermatoglyphic sole and palm patterns in cri-du-chat probands and normal controls. J Men1 Defic Res 1985;29:281-8. IS. Kitsiou-Tzeli S , Dellagrammaticas HD, Papas CB, et al. Unusual ocular findings in an infant with cri-du-chat syndrome. J Med Genet 1983;20:304-7. 16. Persaud TVN, Persaud P. Cardiovascular, respiratory, gastrointestinal, and genitourinary malformations. New York: Alan R. Liss, 1982:16,4O. 17. Yamashita M, Tanioka F, Taniguchi K, et al. Anesthetic considerations in cri-du-chat syndrome: a report of three cases. Anesthesiology 1985;63:201-2.
Special Care in Dentistry, January-February 1990 15
Robert A. Boraz, DDS
Cri-du-chat syndrome: dental considerations and report of case
Cri-du-chat syndrome is a severe disease resulting from a deletion of the short arm of chromosome number 5. The basic medical disorder includes dysmorphic facies, mental retardation, and a striking catlike cry in infancy. Because of significant oral anomalies and difficulty in behavior management, the syndrome is of particular interest to the dental practitioner. A case with many of the typical medical findings and significant dental considerations is reported. An aggressive preventive dentistry program is essential. A thorough understanding of the medical and developmental problems of the patient with cri-duchat syndrome ensures safe and effective dental care.
C
ri-du-chat syndrome (46,XY, 5p-) was first described by Lejeune in 1963.’ In the literature, three females with dysmorphic facies, mental retardation, and a striking catlike cry during infancy were described.’ In all three patients, a deletion of the short arm of a B group chromosome was demonstrated and identified subsequently by autoradiography as number 5 . 2 yMany experts used to consider all autosomal chromosome deletions lethal. Partial deletions of autosomal chromosomes carry a varied prognosis. The overall outlook for quality and length of life has improved greatly for these patients and is thus of significance to dentists.’*The underlying chromosomal aberration has appeared as a new phenomenon in the majority of cases.’ I ’ I 3 Approximately 100 cases of cri-du-chat syndrome have been identified.’
Review of the literature The classic abnormalities associated with cri-du-chat syndrome include low birth weight (less than 2.5 kg), slow growth, catlike cry, mental retardation, hypotonia, microcephaly , facial asymmetry, micrognathia, dental malocclusion, hypertelorism, epicanthal folds, downward slanting palpebral fissures, and congenital heart disease. Other findings in these patients may include cleft lip and palate, myopia, preauricular skin tags, bifid uvula, and an absent kidney or spleen. 2.5.6.12.14.15 Originally, these patients were thought to be profoundly mentally retarded with intelligence quotients in the range of 20 to 30.’ Recent observations have indicated that many children with cri-du-chat syndrome can attain social and developmental skills in the mild to moderate retardation range. Optimal results have been obtained with early infant and childhood training pro-
grams. Linguistic abilities have been the most difficult to influence in a favorable fashion.I3The intelligence of individuals is negatively correlated with the size of the 5p- deletion.I3 The catlike cry associated with cri-duchat syndrome is ascribed to abnormal laryngeal development.2,8Laryngeal webs, presumably remnants of the tissue that temporarily occludes the embryonic larynx, are almost anterior to the vocal cords. The larynx is narrow, and the epiglottis is flaccid, so that it falls back to obstruct the laryngeal inlet and causes stridor. I6 During phonation and crying, the voice is further weakened by air leakage because of failure of the vocal cords to approximate posteriorly and the highpitched mewing cry results from the approximated anterior portion of the vocal cords. As patients get older, the catlike cry is less noticeable and may complicate the late diagnosis of these patients.* Special Care in Dentistry, January-February 1990 13
With a high incidence of congenital heart disease, chronic respiratory infections from aspiration, and mental retardation, dental management of patients with cri-du-chat syndrome can be challenging. As with any patient with mental retardation, obtaining adequate patient management necessary for rendering safe and successful dental treatment may be difficult or impossible. If congenital heart disease is also present, appropriate antibiotic prophylaxis is essential. If general anesthesia is deemed necessary to manage the patient, additional anesthetic risks may result from the congenital heart disease. Retrognathia and a high, vaulted palate may increase the complexity of intubation. Because many infants are hypotonic, the response to muscle relaxants may be accentuated and unpredictable. This places emphasis on giving small doses and monitoring neurornuscular function to avoid the complications associated with respiratory distress. The main anesthetic concerns center around abnormalities in the larynx and upper airway. However, if appropriate care and precautions are taken, general anesthesia can usually be accomplished safely and effectively. ” The cause of cri-du-chat syndrome is the partial deletion of the short arm of chromosome number 5.’ This finding has appeared as a fresh entity in the majority of cases. Two possibilities may explain this genetically: mosaicism and translocation. Support for the theory of translocation comes from the observation that in 10%to 15%of the cases, a balanced translocation in one parent has been identified. These individuals carry an increased risk of occurrence of the syndrome. No similar support for the theory of mosaicism has been identified.’ Report of case
The male patient was born at the University of Kansas Medical Center in 1980. The mother, a 23-year-old female, had delivered a full-term, normal male child 4 1/2 years previously. The first child weighed approximately 7 Ibs. The family history was unremarkable. The mother then took oral contraceptives for 3 years and practiced no birth control for approximately 8 months before conception. She denied any infections, vaginal bleeding, or injuries during pregnancy. Calcium pills and vitamins were the only medications she 14 Special Care in Dentistry, January-February 1990
Fig 1. Facial view of patient. took. While pregnant, the mother indicated she smoked approximately one pack of cigarettes per week and she denied the use of alcoholic beverages. The pregnancy was uncomplicated until the mother noted maternal weight loss in the seventh month and a decided decrease in fetal movement. Two oxytocin challenge tests each demonstrated fetal distress. A sonogram also showed intrauterine growth retardation. The patient was delivered by cesarean section and weighed 1,760 g. He immediately developed respiratory stress syndrome and was placed on positive pressure oxygen via a ventilator. He remained hospitalized in a neonatal intensive care facility for approximately 4 weeks. The patient was hospitalized several times in the next 2 1/2 years, primarily for evaluation of developmental delays and failure to thrive. He did not even start to crawl until 22 months of age. Neurologic evaluation showed a severe developmental delay. He also demonstrated a severe hearing loss of the right ear and a slight loss of the left ear. Chromosome analysis revealed the patient had cri-du-chat syndrome (46,XY, 5p-) with the deletion being of a very significant size. The patient was first examined in the dental clinic at the University of Kansas Medical Center shortly after the diagnosis of his syndrome. Physical evaluation showed severe mental and growth retardation (Fig 1). He demonstrated microcephaly, a bifid uvula, and relative micrognathia (Fig 2). Epicanthal folds were present as well as unusual creases in the fifth fingers. The typical catlike cry associated with cri-du-chat syndrome was apparent. Visual and radiographic evaluation showed several dental carious lesions. An anterior open bite and a high, narrow, vaulted palate were
visible (Fig 3). Because of the recent diagnosis of the anomaly and the questionable ability of the patient to cooperate, the parents deferred treatment at that time. They also refused to consider the alternative of general anesthesia although no congenital heart defect was present. The patient returned for reexamination approximately 1 year later. Several new carious lesions were apparent. Amalgam, composite, and stainless steel crown restorations were safely and effectively provided. A papoose restraint board and chloral hydrate sedation (50 mg/kg) for patient management were used at each of two visits in addition to local anesthesia with 2 % mepivacaine hydrochloride with levonordefrin 1:20,OOO. The patient was alert and awake throughout treatment and cooper-
Fig 2. Patient profile view showing retrognathia.
Fig 3. View of anterior occlusion depicting anterior open bite.
ated at an acceptable level. The patient was carefully and appropriately monitored throughout the procedures. The parents had selected this mode of management over the use of general anesthesia. A thorough preventive dental program was designed and instituted for the patient. This program included the mother’s receiving instruction and demonstrating proficiency with the modified Stillman toothbrushing technique. Instructions included the mother’s brushing the patient’s teeth with a soft bristle toothbrush and use of a fluoride dentifrice twice daily after breakfast and before bedtime. The patient was unable to accomplish this task as demonstrated by the rate of dental caries and an inadequate plaque index. Dental flossing was taught to the patient’s mother with instruction to be performed daily. Home fluoride therapy was desirable but deemed inappropriate as the patient was not able to rinse and expectorate. Nutrition theory and practical recommendations were discussed in depth with an emphasis placed on decreased frequency of sugar intake. A recommendation for recall examinations at least every 3 months was instituted. With the patient being a difficult management problem, the parents were advised of the essential nature of compliance with the preventive program. Three years elapsed before the patient was seen in the dental clinic again as the family had moved away a significant distance. The patient was 8 1/2 years of age and was undergoing an orthodontic and orthopedic evaluation by another practitioner. His records indicated moderate to severe dental crowding of the maxillary and mandibular arches and an Angle Class II skeletal malocclusion as a result of mandibular retrognathia. A large dental overjet had developed. The orthodontist planned to use functional appliances to begin correcting the patient’s dental crowding and retrognathia.
The mother of the patient requested a second opinion on the recommended orthodontic and orthopedic treatment. Review of the records and evaluation of the patient indicated the treatment proposed was appropriate for a compliant patient. However, the patient demonstrated no significant improvement in his ability to cooperate and the mother and practitioner agreed that the treatment prognosis would be highly questionable. The mother decided to proceed with the treatment anyway. Visual examination at the time of the consultation showed a significant improvement in oral hygiene. No new restorations were visually apparent and no new dental problems were noted. The patient did not return for further evaluation nor was information available on the success of the orthodontic treatment. Conclusion
The case of a patient with cri-du-chat syndrome is presented. Oral anomalies that develop in these patients can be difficult to manage because of the associated medical and developmental problems. An aggressive preventive dentistry program is indicated. Behavior management of these patients is usually difficult, as is frequently the case with medically and mentally compromised patients. A thorough understanding of the medical problems of the patient with cri-du-chat syndrome can allow for the safe and effective delivery of dental care that is essential for the attainment of the maximum level of quality of life possible.
Dr. Boraz is associate professor of surgery and pediatrics and director, dental service, University of Kansas Medical Center, 39th and Rainbow Blvd, Kansas City, KS 66103. Address requests for reprints to Dr. Boraz.
I . Lejeune J, Lafouracade 1, Berger, R, et al. Trois cas de deletion partielle du bras court du chromosome 5 . CR Acad Sci [D] (Paris)
1963;257:3098-102. 2. Jones KL. Smith’s recognizable patterns of human malformation. Philadelphia: Saunders, I988:40- I . 3. Wilkins LE, Brown, JA. Nance, WE, et al. Clinical heterogeneity in 80 home reared children with cri-du-chat syndrome. J Pediatr 1983; 102528-33. 4. Berg JM, Delhanty JDA, Faunch JA, et al. Partial deletion of short arm of a chromosome of the 4 and S group (Denver) in an adult male. J Ment Defic Res 1965;9:219-28. 5 . Breg WR, Steele MW, Miller 01, et al. The cri-du-chat syndrome in adolescents and adults: clinical findings in 13 older patients with partial deletion of the short arm of chromosome no. S (5p-). I Pediatr 1970;77:782-91. 6. Sucheston ME, Cannon MS. Congenital malformations. Philadelphia: FA Davis Co, 1973: 15-7. 7. German 1, Lejeune J, Macentyre MN, et al. Chromosomal autoradiography in cri-du-chat syndrome. Cytogenetics I964;3:347-52. 8. Macintyre MN. Stiples WT, La Polla JJ, el al. “The cat cry” syndrome. Am J Dis Child 1964; 108538.42. 9. Wilkins LE, Brown JA, Wolf B. Psychomotor development in 6.5 home-reared children with cri-du-chat syndrome. J Pediatr 1980;97:4O1-5. 10. Behram RE, Vaughan VC. Nelson Textbook of Pediatrics. Philadelphia: Saunders, 1983:302-3. 1 1 , Miller OJ, Breg WR, Warburton D, el al. Partial deletion of the short arm chromosome no. 4 (4p.): clinical studies in five unrelated patients. J Pediatr 1970;77:792-801. 12. Bergsma D, McKusick VA, Ozer FL, et al. The fifth conference on the clinical delineation of birth defects. Part XVI, urinary system and others. Baltimore: Williams and Wilkins , 1974:349-50. 13. Kushnick T, Rao KW, Lamb AN. Familial Sp-syndrome. Clin Genet 1984;26:472-6. 14. Fenger K, Niebuhr E. Discriminant analysis of dermatoglyphic sole and palm patterns in cri-du-chat probands and normal controls. J Men1 Defic Res 1985;29:281-8. IS. Kitsiou-Tzeli S , Dellagrammaticas HD, Papas CB, et al. Unusual ocular findings in an infant with cri-du-chat syndrome. J Med Genet 1983;20:304-7. 16. Persaud TVN, Persaud P. Cardiovascular, respiratory, gastrointestinal, and genitourinary malformations. New York: Alan R. Liss, 1982:16,4O. 17. Yamashita M, Tanioka F, Taniguchi K, et al. Anesthetic considerations in cri-du-chat syndrome: a report of three cases. Anesthesiology 1985;63:201-2.
Special Care in Dentistry, January-February 1990 15
