Journal of Dentistry,
7, No. 4, 1979,
pp. 313-320.
Primed
Orofacial manifestations syndrome (Sp-) Crispian %xlly, Marie-France
in Great Britain
in the Cri du Chat
MB BS, BDS, BSc”
Davison,
RNMS
Harperbury Hospital, Radlett, Hem.,
UK
INTRODUCTION The Cri du Chat syndrome
(Crying Cat Syndrome) (Lejeune et al., 1963) is a rare chromosome abnormality characterized by a distinctive cry in association with orofacial anomalies, mental handicap and a number of other abnormalities. The four cases presented here appear to be the first reported in the dental literature. The Cri du Chat syndrome is a rare autosomal abnormality in which there is deletion of part of the short arm of chromosome 5, one of the B group of chromosomes, and the condition is therefore designated as 5 p- (Lejeune et al., 1963, 1964; German et al., 1964; Miller et al., 1969b). While the majority of cases are due to simple deletions, some IO-15 per cent are due to translocations (de Capoa et al., 1967; Warburton and Miller, 1967) and a few are mosaics (Zellweger, 1966; Antich et al., 1968; Mennicken et al., 1968; Neuhauser et a1.,1968). It became apparent following the early case reports, that some patients, while having deletions of the short arm of a B group chromosome, had different phenotypes from the Cri du Chat syndrome. This group of patients was characterized by multiple midline fusion defects including palatal clefts, and it is now clear that the deletion is of the short arm of chromosome 4 (Hirschhorn and Cooper, 1961; Gustavson et al., 1964; Hirschhorn et al., 1965; Wolf et al., 1965). This latter syndrome is termed the Wolf-Hirschhorn syndrome (Wolf et al., 1965) which, although similar to the Cri du Chat syndrome, is a more severe anomaly (Polani, 1969). The Cri du Chat syndrome is a very rare condition. The prevalence in the general population is 1 in 50 000 to 1 in 100 000 (Polani, 1969) and even in the severely mentally handicapped population it is less than 1 per cent (Gorlin, 1974). The majority of patients are female (Taylor, 1967; Polani, 1969; Gorlin 1974) although this is less obvious in the older age groups (Polani, 1969; Breg et al., 1970). The aetiology of the chromosome anomaly is unknown and there is no parental age influence (Polani, 1969; Taylor, 1969; Goodman and Gorlin, 1977). General manifestations The common features include neurological, cutaneous and possibly cardiac and skeletal defects. Most cases are of low birth weight (Taylor, 1969; Gorlin, 1974) and are later characterized by short stature. Many patients survive to adulthood in spite of their severe handicap (Breg at al., 1970).
*Present Address: School, Glasgow.
University
Department
of Oral Medicine
and Pathology,
Glasgow
Dental
Hospital
and
314
Journal of Dentistry,
Vol. ~/NO. 4
Neurological abnormalities Severe mental handicap is a prominent finding, the intelligence quotient usually falling below 30 (Hijmans and Shearn, 1965). Most of the patients are thus institutionalized. The characteristic cry is heard mainly during early infancy and tends to abate with age (McCracken and Gordon, 1965; Gordon and Cooke, 1968; Breg et al., 1970). The infant utters a plaintive monotone, weak and shrill cry similar to that of a mewing cat, being almost one octave higher than normal (Schroeder et al., 1967). Although there may be minor laryngeal malformations (Lejeune et al., 1964; Macintyre et al., 1964; Micheau and Schlumberger, 1968) it is probable that the abnormal cry is neurological in origin (Schroeder et al., 1967; Micheau and Schlumberger, 1968). The cry is now known not to be absolutely specific and may occur in a variety of neurological disorders (Granoff and Preston, 1971). The young patient with the Cri du Chat syndrome may be hypotonic (Lejeune et al., 1963; Taylor, 1967; Miller et al., 1969a; Breg et al., 1970) but hypertonia is frequently seen in adults (Schreegans et al., 1966; Platt and Holmes, 1971).
Cutaneous manifestations Dermatoglyphic characteristics include cent of patients; a distal axial triradius, a deficiency of ulnar loops (Warburton 1969). Cutaneous haemangiomata may Schmid and Vischer, 1967).
a single transverse (simian) palmar crease in 35 per and mainly arches and whorls on the fingertips with and Miller, 1967; Mennicken et al., 1968; Valentine, uncommonly occur (Milunsky and Chitham, 1966;
Cardiac abnormalities Congenital cardiac defects are found in 20 per cent of patients with Cri du Chat syndrome (Taylor, 1967). The most common defect is a ventricular septal defect, but other lesions such as a patent ductus arteriosus may occur (Cavalieri et al., 1964; Lejeune et al., 1964; Genest et al., 1965; Giorgi et al., 1965).
Other abnormalities The various skeletal abnormalities which may occur include scoliosis, small ilia, syndactyly, small metatarsals and metacarpals, and talipes equinovarus (Neuhauser and Lother, 1966; Mennicken et al., 1968; Goodman and Gorlin, 1977). Genito-urinary defects may be present (Goodman and Gorlin, 1977).
Orofacial manifestations Microcephaly is a prominent finding and occurs in association with brachycephaly and a typical rounded ‘moon face’ (Taylor, 1967; Polani, 1969; Sedan0 et al., 1971). The frontal sinuses are often large and the frontal bossing may mask the microcephaly (S&mid and Vischer, 1967). The nasal bridge is broad and this together with the presence ofepicanthic folds contributes to an apparent hypertelorism (Sedan0 et al., 1971). The palpebral fissures have an antimongoloid slope and there may be strabismus; the facial appearance is thus quite distinct from the common autosomal anomaly, Down’s syndrome (Scully, 1973). The pupillary response to methacholine is abnormal (Howard, 1972). The abnormal facial appearance of the child with the Cri du Chat syndrome seems to become less characteristic with age (Gordon and Cooke, 1968) but other features such as premature greying of the hair may appear (Breg et al., 1970). Low set ears, with preauricular appendages are seen in
Scully and Davison: Cri du Chat syndrome
Fig. 1. Case 1. Hypertelorism, bridge and microcephaly.
prominent
Fig. 3. Case 1. Karyotype
nasal
Fig. 2. Case 1. Lateral skull large frontal microcephaly, pituitary fossa.
by G banding (trypsin).
(Deletion
radiograph showing sinuses and small
arrowed.)
some cases (Dyggve and Mikkelson, 1965; Hijmans and Shearn, 1965). Mandibular retrognathia occurs in 75 per cent of patients (Taylor, 1967; Sedan0 et al., 1971; Goodman and Gorlin, 1977) and the palate is high in 50 per cent (Hustinx and Wiffels, 1965; Ricci et al., 1965; Milunsky and Chitham, 1966; Sedan0 et al., 1971) but rarely cleft (Olive et al., 1968). Malocclusion is almost invariable (Taylor, 1967; Gordon and Cooke, 1968; Mennicken et al., 1968; Breg et al., 1970; Niebuhr, 1971; Sedan0 et al., 1971) and in 5 of 9 patients reviewed by Sedan0 et al. (197 1) enamel hypoplasia was reported. CASE REPORTS Case 1: A 44-yearold
caucasian male who had been admitted to an institution for the mentally handicapped at the age of 7 years because of profound mental and physical handicap, being unable to walk or talk at that age. The past medical history included episodes of shigella gastroenteritis in 1957 and viral B hepatitis in 1973. The patient was first examined in 1974. He was severely mentally handicapped with a bilateral sensorineural deafness. Physical examination revealed short stature and a severe kyphosis, but no cardiac
316
Journal of Dentistry, Vol. ~/NO. 4
Fig. 4. Case 2. Karyotype (Deletion arrowed.).
showing deletion of short arm of chromosome 6
Fig. 5. Case 2. Marked microcephaly, hypertelorism and retrognathism.
Fig. 6. Case 2. Lateral skull radiograph showing marked microcephaly, large frontal sinuses and small pituitary fossa (cf Fig. 1).
abnormality. He demonstrated craniofacial features typical of the Cri du Chat syndrome, especially microcephaly, grey hair, frontal bossing, a prominent nasal bridge and antimongoloid slopes to the palpebral fissures, but there was no mandibular retrognathia (Fig. I). The patient was partially edentulous; &$$+
were present, and all were hypoplastic.
There was no detectable caries, but oral hygiene
was poor, and there was advanced generalized chronic periodontitis. There were no mucosal abnormalities detected. The palate was deeply vaulted, but otherwise appeared normal. A lateral skull radiography confirmed marked microcephaly and revealed extensively pneumatized frontal sinuses and a small pituitary fossa (Fig. Z), but it was impossible to carry out oral radiographic studies. The karyotype was characteristic of the Cri du Chat syndrome 46 XY 5p- (Fig. 3). In view of the past history of hepatitis, the patient was screened for hepatitis B surface antigen (HbsAg) which proved to be negative. The prognosis for the severely periodontally involved teeth was poor and a clearance was carried out under general anaesthesia. Full dentures were then constructed. Two years later the patient developed increasing dysphagia for both solids and liquids. A barium swallow examination demonstrated a lower oesophageal carcinomatous stricture and chest radiography revealed multiple osteolytic areas in several ribs, attributed to metastases. Unfortunately the patient succumbed rapidly before effective therapy could be instituted.
317
Scully and Davison: Cri du Chat syndrome
fig. 8. Case 3. Bifid uvula.
Fig. 7. Case 3. Typical facial appearance of patients with the Cri du Chat syndrome: hyoertelorism, antimongoloid slope to palpebral fissures and epicanthi.
Fig. 9. Case 4. Hypertelorism two cavernous haemangiometa
and epicanthi are prominent in the right frontal region.
in this patient
who has
318
Journal of Dentistry, Vol. ~/NO. 4
Case 2: A 50-year&l female caucasian who had been admitted to an institution at the age of 22 years because of severe developmental retardation. Her karyotype was consistent with the diagnosis of the Cri du Chat syndrome 46 XX 5 p- (Fig 4). The patient had a recurrent history of menorrhagia, but no other relevant medical history. The patient was fust examined in 1975 and was seen to be severely mentally handicapped with no cardiorespiratory or abdominal abnormalities. She had the facial features of the Cri du Chat syndrome with microcephaly, a broad nasal bridge, antimongoloid slopes to the palpebral fissures, grey hair and mandibular retrognathia (Fig. 5). Oral examination revealed that the patient was almost edentulous, the only remaining teeth being 54311 3 and these teeth were markedly mobile due to advanced chronic periodontitis. The palate was high but otherwise normal. The oral mucosa was pale, and there was depapillation of the anterior third of the dorsum of the tongue consistent with an anaemia. Haematological examination revealed an iron deficiency anaemia, presumably secondary to the menorrhagia. Microcephaly and large frontal sinuses were seen on the skull radiograph (Fig. 6). Dental treatment was deferred, in view of the physical findings, and the patient was referred for a gynaecological opinion. The menorrhagia was found to be due to a vaginal carcinoma but the patient unfortunately succumbed in spite of radiotherapy to the carcinoma.
Case 3: An 11-yearald Caucasian male who had been admitted to an institution at the age of 3 years because of severe mental handicap. The patient had giardiasis in 1973 and had suffered from recurrent urinary and respiratory infections. He was aJlergic to penicillin. The karyotype was consistent with a diagnosis of the Cri du Chat syndrome (46 XY 5 p-). This patient was below the third percentile for weight and height. Physical examination revealed an extremely retarded child with a severe head-banging habit. He had a small ventricular septal defect but there were no abnormal respiratory or abdominal findings. He was noted to have microcephaly and his appearance was characteristic of the Cri du Chat syndrome with a broad nasal bridge, hypertelorism, antimongoloid sloping of the palpebral f=sures, marked epicanthi and low set ears (Fig. 7). His hair was very fine and fair. At the time of the first examination there was marked retardation of eruption, the only EDC;; 1;;c”XX& The 2J2,, teeth present in the mouth being EDC re erupting and the m were carious. The oral hygiene was poor and there was generalized chronic marginal gingivitis. No mucosal abnormalities were detected. The palate was high and the uvula bifid (Fig. 8). Conservative treatment of m was carried out under local anaesthesia. Scaling and polishing was carried out under an erythromycin antibiotic ‘cover’ in view of the wdiac defect. By the age of 15 years g anterior crowding.
were erupting into the mouth, all in a labial malocclusion with marked
Case 4: A 20~month-old Caucasian female who was severely retarded, being unable to stand or talk. The child was below the third percentile for weight and height and had a developmental age of about 7 months. There were no detectable cardiorespiratory defects. She had marked hypertelorism and this with the presence of epicanthic folds contributed to a pseudo-strabismus. She was also microcephalic and the fontanelles were unclosed, and on her right forehead at the hairline were two large cavernous haemangiomata each measuring some 2 cm in diameter (Fig. 9). There was marked retardation of tooth eruption, only m being present in the mouth, although these teeth appeared morphologically normal. There were no other demonstrable oral anomalies. Chromosome analysis confirmed the diagnosis of the Cri du Chat
syndrome.
DISCUSSION 4 patients demonstrated many of the features of the Cri du Chat syndrome. All patients were phenotypically similar and had obvious facial features of the syndrome. All were severely mentally handicapped, but only 1 had a detectable cardiac anomaly. The problems of institutional care are highlighted by the histories of infections with shigella, Giardia lamblia and hepatitis virus - all common in such environments. Three patients had high arched palate and in 1 the uvula was bifid. Two patients had obvious retardation of tooth eruption but since the other patients were seen at a much later age, eruption times could not be ascertained. It was impossible to assess malocculsion in 3 patients but 1 had anterior segment crowding (Case 3). No obvious microdontia was noted. The 2 older patients succumbed from carcinomata at a relatively early age; whether patients with this condition are at an increased risk from neoplasia however remains to be substantiated. These
Scully and Davison: Cri du Chat syndrome
319
Acknowledgements My thanks are due to Dr M. Ridler, Kennedy Galton Centre, Harperbury Hospital, for providing the chromosome studies, and to Dr J. Badham and Dr M. Grant (Consultant Psychiatrists) for permission to report patients under their care. REFERENCES Antich J., Ribas-Mundo M., Pratos J. et al. (1968) Cri du Chat with chromosomal mosaicism. Lancet 1, 538. Breg W. R., Steele M. W., Miller 0. J. et al. (1970) The cri du chat syndrome in adolescents and adults: clinical findings in 13 older patients with partial deletion of the short arms of chromosome no. 5 (Sp-).J. Pediat. 77,782-791. de Capoa A., Warburton D., Breg W. R. et al. (1967) Translocation heterozygosis: a cause of five cases of the cri du chat syndrome and two cases with a duplication of chromosome number five in three families. Am. J. Human Genet. 19, 586-603. Cavalieri S., Mastella G. and Tiepolo L. (1964) The ‘cri du chat’ syndrome. La sindrome della vote da gatto. Fracastoro 57,369. Dyggve H. S. and Mikkelson M. (1965) Partial deletion of the short arms of a chromosome of the 4-5 Group (Denver). Arch. Dis. Child. 40,82-85. Genest P., Tremblay M. and Mortezai M. (1965) Le syndrome du ‘cri du chat’. Etude d’un cas de deletion partielle du bras court du chromosomes et translocation au chromosome 4. Lava1 Med. 36, 3 19. German J., Lejeune J., Macintyre M. et al. (1964) Chromosomal autoradiography in the cri du chat syndrome. Cytogenetics 3,347-352. Giorgi P. L., Ceccarelli M. and Paci A. (1965) Su un case di sindrome de1 ‘cri du chat’ con peculari anomahe fenotipiche. Minerva Pediat. 17, 1972-1975. Goodman R. M. and Gorlin R. J. (1977) AtZas of the Face in Genetic Disorders. 2nd ed. St Louis, Mosby, p. 140. Gordon R. R. and Cooke P. (1968) Facial appearance in cri du chat syndrome. Develop. Med. Child. Neural. 10, 69-76. Gorlin R. J. (1974) 1n:Yunis J. J. (ed.) Clinical Manifestations of Chromosome Disorders in Human Chromosome Methodology. 2nd ed. New York, Academic Press, pp. 197-270. Granoff D. M. and Preston M. S. (1971) Cri-du-Chat syndrome - an unhelpful designation. Lancet 2,99-l 00. Gustavson K. H., Finley S. C., Finley W. H. et al. (1964) A 4-5/21-22 chromosomal translocation associated with multiple congenital anomalies. Acta Paediat. 53, 172. Hijmans J. D. and Shearn D. B. (1965) Partial deletion of short arms of chromosome no. 5. Am. J. Dis. Child. 109, 85-89. Hirschhorn K. and Cooper H. L. (196 1) Apparent deletion of short arms of one chromosome (4 or 5) in a child with defects of midline fusion. Hum. Chrom, Newsletter 4, 14. Hirschhorn K., Cooper H. L. and Firschein I. L. (1965) Deletion of short arms of chromosome 4-5 in a child with defects of midline fusion. Humangenetik 1,479-482. Howard R. 0. (1972) Ocular abnormalities in the cri-du-chat syndrome. Am. J. Dis. Child. 73,949-954. Hustinx T . W. and Wiffels J. C. H. M. (1965) ‘Cri du chat’ syndrome. Lancet 2, 135- 136. Lejeune J., Lafourcade J., Berger R. et al. (1963) Trois cas de deletion partielle du bras court d’un chromosome 5. Acad. Sci. Parts 257,3098-3 102. Lejeune J., Lafourcade J., deGrouchy J. et al. (1964) Deletion partielle du bras court du chromosome 5. Individualisation d’un nouvel etat morbide. Sem. Hc?p. Parts 40, 106%1071.
320
Journal of Dentistry, Vol. ~/NO. 4
McCracken J. S. and Gordon R. R. (1965) ‘Cri du Chat’ syndrome, a new clinical and cytogenetic entity. Lancer 1,23-25. Macintyre M. N., Staples W. I., LaPolla J. et al. (1964) The ‘catcry’ syndrome. Am. J. Dis. Child. 108, 5388542.
Mennicken U., Pfeiffer R., Puhn U. et al. (1968) Klinische und cytogenetische Befunde von 7 patenten mit Cri-du-Chat Syndrome. 2. Kinderheilkd. 114,278-281. Micheau C. and Schlumberger J. R. (1968) Etude anatomopatholoque du larynx dans la maladie du cri du chat. Ann. Pediat. 15, 748. Miller 0. J., Warburton D. and Breg W. R. (1969a) Deletions of group B chromosomes. Proc. first conf. on clin. delineation of Birth Defects. Part V. Phenotypic Aspects of Chromosomal Aberrations. ed. Bergma D in Birth Defects. Orginal Article Series. Vol V 5.100 (1969). Miller D. A., Warburton D. and Miller 0. J. (1969b) Clustering in deleted short arm length among 25 cases with a Bp- chromosome. Cytogenetics 8, 109-l 16. Milunsky A. and Chitham R. G. (1966) The Cri du Chat syndr0me.J. Ment. Defic. Res. 10, 153-157. Neuhauser G. and Lother K. (1966) Das Katzenschrei Syndrom. Monatsschr. Kinderheilkd. 114,278-281.
Neuhauser G., Singer H. and Zang K. (1968) Cri du chat syndrom mit chromosomenmosaik 46XY/46XY 5p-. Humangenetik 5,3 15-320. Niebuhr E. (1971) The cat cry syndrome (5p-) in adolescents and adults. J. Ment. Defic. Res. 15,277-291. Olive D., Gilgenkrantz S., Cabrol C. et al. (1968) Maladie du cri du chat (5p-) avec gueule de loup. Pediatrie 23, 795. Platt M. and Holmes L. B. (1971) Hypertonia in older patients with the 5p- syndrome. Lancet 2, 1429.
Polani P. E. (1969)
Autosomal
imbalance
and its syndromes
excluding
Down’s Br. Med.
Bull. 25, 81-93.
Ricci N., Ventimiglia B., Dallapiocalla B. et al. (1965) 1278-1279. Schmid V. and Vischer D. (1967) Cri-du-Chat syndrome.
‘Cri du chat’ syndrome.
Lancet
1,
Case Report. Heluet. Paediat. Acta
22,22.
Schreegans E., Rohmer A., Levy-Silagy J. et al. (1966) Un cas de maladie du cri du chat. Deletion partielle du bras court du chromosome 5. Pediatrie 21, 823. Schroeder H., Schleiermacher E., Schroeder T. et al. (1967) Zur klinischen differential diagnose der Cri du Chat syndroms. Humangenetik 4, 294-304. Scully C. (1973) Down’s Syndrome. Br. J. Hosp. Med. 10, 186-l 96. Sedan0 H. O., Look R. A., Carter C. et al. (1971) B group short-arm deletion syndromes. Birth Defects. Orginal Article Series. VII. 89-97. Taylor A. I. (1967) Patau’s, Edward’s and cri du chat syndromes: a tabulated summary of current findings. Develop. Med. Child. Neural. 9, 76-86. Taylor J. H. (1969) In: Caspari E. W. and Ravin A. W. (ed.) Genetic Urganisation. VoZ 1. New York, Academic Press, p. 163. Valentine G. M. (1969) The Chromosome Disorders. 2nd ed. London, Heinemann. Warburton D. and Miller 0. J. (1967) Dermatoglyphic features of patients with a partial short arm deletion of a B group chromosome. Ann. Human Genet. 31, 189-208. Wolf U., Reinwein H., Porsch R. et al. (1965) Defizienz an den kurzen Armen eines chromosomes Nr 4. Humangenetik 1,397-413. Zellweger H. (1966) Cri du chat with chromosomal mosaicism. Lancet 2, 57.
7, No. 4, 1979,
pp. 313-320.
Primed
Orofacial manifestations syndrome (Sp-) Crispian %xlly, Marie-France
in Great Britain
in the Cri du Chat
MB BS, BDS, BSc”
Davison,
RNMS
Harperbury Hospital, Radlett, Hem.,
UK
INTRODUCTION The Cri du Chat syndrome
(Crying Cat Syndrome) (Lejeune et al., 1963) is a rare chromosome abnormality characterized by a distinctive cry in association with orofacial anomalies, mental handicap and a number of other abnormalities. The four cases presented here appear to be the first reported in the dental literature. The Cri du Chat syndrome is a rare autosomal abnormality in which there is deletion of part of the short arm of chromosome 5, one of the B group of chromosomes, and the condition is therefore designated as 5 p- (Lejeune et al., 1963, 1964; German et al., 1964; Miller et al., 1969b). While the majority of cases are due to simple deletions, some IO-15 per cent are due to translocations (de Capoa et al., 1967; Warburton and Miller, 1967) and a few are mosaics (Zellweger, 1966; Antich et al., 1968; Mennicken et al., 1968; Neuhauser et a1.,1968). It became apparent following the early case reports, that some patients, while having deletions of the short arm of a B group chromosome, had different phenotypes from the Cri du Chat syndrome. This group of patients was characterized by multiple midline fusion defects including palatal clefts, and it is now clear that the deletion is of the short arm of chromosome 4 (Hirschhorn and Cooper, 1961; Gustavson et al., 1964; Hirschhorn et al., 1965; Wolf et al., 1965). This latter syndrome is termed the Wolf-Hirschhorn syndrome (Wolf et al., 1965) which, although similar to the Cri du Chat syndrome, is a more severe anomaly (Polani, 1969). The Cri du Chat syndrome is a very rare condition. The prevalence in the general population is 1 in 50 000 to 1 in 100 000 (Polani, 1969) and even in the severely mentally handicapped population it is less than 1 per cent (Gorlin, 1974). The majority of patients are female (Taylor, 1967; Polani, 1969; Gorlin 1974) although this is less obvious in the older age groups (Polani, 1969; Breg et al., 1970). The aetiology of the chromosome anomaly is unknown and there is no parental age influence (Polani, 1969; Taylor, 1969; Goodman and Gorlin, 1977). General manifestations The common features include neurological, cutaneous and possibly cardiac and skeletal defects. Most cases are of low birth weight (Taylor, 1969; Gorlin, 1974) and are later characterized by short stature. Many patients survive to adulthood in spite of their severe handicap (Breg at al., 1970).
*Present Address: School, Glasgow.
University
Department
of Oral Medicine
and Pathology,
Glasgow
Dental
Hospital
and
314
Journal of Dentistry,
Vol. ~/NO. 4
Neurological abnormalities Severe mental handicap is a prominent finding, the intelligence quotient usually falling below 30 (Hijmans and Shearn, 1965). Most of the patients are thus institutionalized. The characteristic cry is heard mainly during early infancy and tends to abate with age (McCracken and Gordon, 1965; Gordon and Cooke, 1968; Breg et al., 1970). The infant utters a plaintive monotone, weak and shrill cry similar to that of a mewing cat, being almost one octave higher than normal (Schroeder et al., 1967). Although there may be minor laryngeal malformations (Lejeune et al., 1964; Macintyre et al., 1964; Micheau and Schlumberger, 1968) it is probable that the abnormal cry is neurological in origin (Schroeder et al., 1967; Micheau and Schlumberger, 1968). The cry is now known not to be absolutely specific and may occur in a variety of neurological disorders (Granoff and Preston, 1971). The young patient with the Cri du Chat syndrome may be hypotonic (Lejeune et al., 1963; Taylor, 1967; Miller et al., 1969a; Breg et al., 1970) but hypertonia is frequently seen in adults (Schreegans et al., 1966; Platt and Holmes, 1971).
Cutaneous manifestations Dermatoglyphic characteristics include cent of patients; a distal axial triradius, a deficiency of ulnar loops (Warburton 1969). Cutaneous haemangiomata may Schmid and Vischer, 1967).
a single transverse (simian) palmar crease in 35 per and mainly arches and whorls on the fingertips with and Miller, 1967; Mennicken et al., 1968; Valentine, uncommonly occur (Milunsky and Chitham, 1966;
Cardiac abnormalities Congenital cardiac defects are found in 20 per cent of patients with Cri du Chat syndrome (Taylor, 1967). The most common defect is a ventricular septal defect, but other lesions such as a patent ductus arteriosus may occur (Cavalieri et al., 1964; Lejeune et al., 1964; Genest et al., 1965; Giorgi et al., 1965).
Other abnormalities The various skeletal abnormalities which may occur include scoliosis, small ilia, syndactyly, small metatarsals and metacarpals, and talipes equinovarus (Neuhauser and Lother, 1966; Mennicken et al., 1968; Goodman and Gorlin, 1977). Genito-urinary defects may be present (Goodman and Gorlin, 1977).
Orofacial manifestations Microcephaly is a prominent finding and occurs in association with brachycephaly and a typical rounded ‘moon face’ (Taylor, 1967; Polani, 1969; Sedan0 et al., 1971). The frontal sinuses are often large and the frontal bossing may mask the microcephaly (S&mid and Vischer, 1967). The nasal bridge is broad and this together with the presence ofepicanthic folds contributes to an apparent hypertelorism (Sedan0 et al., 1971). The palpebral fissures have an antimongoloid slope and there may be strabismus; the facial appearance is thus quite distinct from the common autosomal anomaly, Down’s syndrome (Scully, 1973). The pupillary response to methacholine is abnormal (Howard, 1972). The abnormal facial appearance of the child with the Cri du Chat syndrome seems to become less characteristic with age (Gordon and Cooke, 1968) but other features such as premature greying of the hair may appear (Breg et al., 1970). Low set ears, with preauricular appendages are seen in
Scully and Davison: Cri du Chat syndrome
Fig. 1. Case 1. Hypertelorism, bridge and microcephaly.
prominent
Fig. 3. Case 1. Karyotype
nasal
Fig. 2. Case 1. Lateral skull large frontal microcephaly, pituitary fossa.
by G banding (trypsin).
(Deletion
radiograph showing sinuses and small
arrowed.)
some cases (Dyggve and Mikkelson, 1965; Hijmans and Shearn, 1965). Mandibular retrognathia occurs in 75 per cent of patients (Taylor, 1967; Sedan0 et al., 1971; Goodman and Gorlin, 1977) and the palate is high in 50 per cent (Hustinx and Wiffels, 1965; Ricci et al., 1965; Milunsky and Chitham, 1966; Sedan0 et al., 1971) but rarely cleft (Olive et al., 1968). Malocclusion is almost invariable (Taylor, 1967; Gordon and Cooke, 1968; Mennicken et al., 1968; Breg et al., 1970; Niebuhr, 1971; Sedan0 et al., 1971) and in 5 of 9 patients reviewed by Sedan0 et al. (197 1) enamel hypoplasia was reported. CASE REPORTS Case 1: A 44-yearold
caucasian male who had been admitted to an institution for the mentally handicapped at the age of 7 years because of profound mental and physical handicap, being unable to walk or talk at that age. The past medical history included episodes of shigella gastroenteritis in 1957 and viral B hepatitis in 1973. The patient was first examined in 1974. He was severely mentally handicapped with a bilateral sensorineural deafness. Physical examination revealed short stature and a severe kyphosis, but no cardiac
316
Journal of Dentistry, Vol. ~/NO. 4
Fig. 4. Case 2. Karyotype (Deletion arrowed.).
showing deletion of short arm of chromosome 6
Fig. 5. Case 2. Marked microcephaly, hypertelorism and retrognathism.
Fig. 6. Case 2. Lateral skull radiograph showing marked microcephaly, large frontal sinuses and small pituitary fossa (cf Fig. 1).
abnormality. He demonstrated craniofacial features typical of the Cri du Chat syndrome, especially microcephaly, grey hair, frontal bossing, a prominent nasal bridge and antimongoloid slopes to the palpebral fissures, but there was no mandibular retrognathia (Fig. I). The patient was partially edentulous; &$$+
were present, and all were hypoplastic.
There was no detectable caries, but oral hygiene
was poor, and there was advanced generalized chronic periodontitis. There were no mucosal abnormalities detected. The palate was deeply vaulted, but otherwise appeared normal. A lateral skull radiography confirmed marked microcephaly and revealed extensively pneumatized frontal sinuses and a small pituitary fossa (Fig. Z), but it was impossible to carry out oral radiographic studies. The karyotype was characteristic of the Cri du Chat syndrome 46 XY 5p- (Fig. 3). In view of the past history of hepatitis, the patient was screened for hepatitis B surface antigen (HbsAg) which proved to be negative. The prognosis for the severely periodontally involved teeth was poor and a clearance was carried out under general anaesthesia. Full dentures were then constructed. Two years later the patient developed increasing dysphagia for both solids and liquids. A barium swallow examination demonstrated a lower oesophageal carcinomatous stricture and chest radiography revealed multiple osteolytic areas in several ribs, attributed to metastases. Unfortunately the patient succumbed rapidly before effective therapy could be instituted.
317
Scully and Davison: Cri du Chat syndrome
fig. 8. Case 3. Bifid uvula.
Fig. 7. Case 3. Typical facial appearance of patients with the Cri du Chat syndrome: hyoertelorism, antimongoloid slope to palpebral fissures and epicanthi.
Fig. 9. Case 4. Hypertelorism two cavernous haemangiometa
and epicanthi are prominent in the right frontal region.
in this patient
who has
318
Journal of Dentistry, Vol. ~/NO. 4
Case 2: A 50-year&l female caucasian who had been admitted to an institution at the age of 22 years because of severe developmental retardation. Her karyotype was consistent with the diagnosis of the Cri du Chat syndrome 46 XX 5 p- (Fig 4). The patient had a recurrent history of menorrhagia, but no other relevant medical history. The patient was fust examined in 1975 and was seen to be severely mentally handicapped with no cardiorespiratory or abdominal abnormalities. She had the facial features of the Cri du Chat syndrome with microcephaly, a broad nasal bridge, antimongoloid slopes to the palpebral fissures, grey hair and mandibular retrognathia (Fig. 5). Oral examination revealed that the patient was almost edentulous, the only remaining teeth being 54311 3 and these teeth were markedly mobile due to advanced chronic periodontitis. The palate was high but otherwise normal. The oral mucosa was pale, and there was depapillation of the anterior third of the dorsum of the tongue consistent with an anaemia. Haematological examination revealed an iron deficiency anaemia, presumably secondary to the menorrhagia. Microcephaly and large frontal sinuses were seen on the skull radiograph (Fig. 6). Dental treatment was deferred, in view of the physical findings, and the patient was referred for a gynaecological opinion. The menorrhagia was found to be due to a vaginal carcinoma but the patient unfortunately succumbed in spite of radiotherapy to the carcinoma.
Case 3: An 11-yearald Caucasian male who had been admitted to an institution at the age of 3 years because of severe mental handicap. The patient had giardiasis in 1973 and had suffered from recurrent urinary and respiratory infections. He was aJlergic to penicillin. The karyotype was consistent with a diagnosis of the Cri du Chat syndrome (46 XY 5 p-). This patient was below the third percentile for weight and height. Physical examination revealed an extremely retarded child with a severe head-banging habit. He had a small ventricular septal defect but there were no abnormal respiratory or abdominal findings. He was noted to have microcephaly and his appearance was characteristic of the Cri du Chat syndrome with a broad nasal bridge, hypertelorism, antimongoloid sloping of the palpebral f=sures, marked epicanthi and low set ears (Fig. 7). His hair was very fine and fair. At the time of the first examination there was marked retardation of eruption, the only EDC;; 1;;c”XX& The 2J2,, teeth present in the mouth being EDC re erupting and the m were carious. The oral hygiene was poor and there was generalized chronic marginal gingivitis. No mucosal abnormalities were detected. The palate was high and the uvula bifid (Fig. 8). Conservative treatment of m was carried out under local anaesthesia. Scaling and polishing was carried out under an erythromycin antibiotic ‘cover’ in view of the wdiac defect. By the age of 15 years g anterior crowding.
were erupting into the mouth, all in a labial malocclusion with marked
Case 4: A 20~month-old Caucasian female who was severely retarded, being unable to stand or talk. The child was below the third percentile for weight and height and had a developmental age of about 7 months. There were no detectable cardiorespiratory defects. She had marked hypertelorism and this with the presence of epicanthic folds contributed to a pseudo-strabismus. She was also microcephalic and the fontanelles were unclosed, and on her right forehead at the hairline were two large cavernous haemangiomata each measuring some 2 cm in diameter (Fig. 9). There was marked retardation of tooth eruption, only m being present in the mouth, although these teeth appeared morphologically normal. There were no other demonstrable oral anomalies. Chromosome analysis confirmed the diagnosis of the Cri du Chat
syndrome.
DISCUSSION 4 patients demonstrated many of the features of the Cri du Chat syndrome. All patients were phenotypically similar and had obvious facial features of the syndrome. All were severely mentally handicapped, but only 1 had a detectable cardiac anomaly. The problems of institutional care are highlighted by the histories of infections with shigella, Giardia lamblia and hepatitis virus - all common in such environments. Three patients had high arched palate and in 1 the uvula was bifid. Two patients had obvious retardation of tooth eruption but since the other patients were seen at a much later age, eruption times could not be ascertained. It was impossible to assess malocculsion in 3 patients but 1 had anterior segment crowding (Case 3). No obvious microdontia was noted. The 2 older patients succumbed from carcinomata at a relatively early age; whether patients with this condition are at an increased risk from neoplasia however remains to be substantiated. These
Scully and Davison: Cri du Chat syndrome
319
Acknowledgements My thanks are due to Dr M. Ridler, Kennedy Galton Centre, Harperbury Hospital, for providing the chromosome studies, and to Dr J. Badham and Dr M. Grant (Consultant Psychiatrists) for permission to report patients under their care. REFERENCES Antich J., Ribas-Mundo M., Pratos J. et al. (1968) Cri du Chat with chromosomal mosaicism. Lancet 1, 538. Breg W. R., Steele M. W., Miller 0. J. et al. (1970) The cri du chat syndrome in adolescents and adults: clinical findings in 13 older patients with partial deletion of the short arms of chromosome no. 5 (Sp-).J. Pediat. 77,782-791. de Capoa A., Warburton D., Breg W. R. et al. (1967) Translocation heterozygosis: a cause of five cases of the cri du chat syndrome and two cases with a duplication of chromosome number five in three families. Am. J. Human Genet. 19, 586-603. Cavalieri S., Mastella G. and Tiepolo L. (1964) The ‘cri du chat’ syndrome. La sindrome della vote da gatto. Fracastoro 57,369. Dyggve H. S. and Mikkelson M. (1965) Partial deletion of the short arms of a chromosome of the 4-5 Group (Denver). Arch. Dis. Child. 40,82-85. Genest P., Tremblay M. and Mortezai M. (1965) Le syndrome du ‘cri du chat’. Etude d’un cas de deletion partielle du bras court du chromosomes et translocation au chromosome 4. Lava1 Med. 36, 3 19. German J., Lejeune J., Macintyre M. et al. (1964) Chromosomal autoradiography in the cri du chat syndrome. Cytogenetics 3,347-352. Giorgi P. L., Ceccarelli M. and Paci A. (1965) Su un case di sindrome de1 ‘cri du chat’ con peculari anomahe fenotipiche. Minerva Pediat. 17, 1972-1975. Goodman R. M. and Gorlin R. J. (1977) AtZas of the Face in Genetic Disorders. 2nd ed. St Louis, Mosby, p. 140. Gordon R. R. and Cooke P. (1968) Facial appearance in cri du chat syndrome. Develop. Med. Child. Neural. 10, 69-76. Gorlin R. J. (1974) 1n:Yunis J. J. (ed.) Clinical Manifestations of Chromosome Disorders in Human Chromosome Methodology. 2nd ed. New York, Academic Press, pp. 197-270. Granoff D. M. and Preston M. S. (1971) Cri-du-Chat syndrome - an unhelpful designation. Lancet 2,99-l 00. Gustavson K. H., Finley S. C., Finley W. H. et al. (1964) A 4-5/21-22 chromosomal translocation associated with multiple congenital anomalies. Acta Paediat. 53, 172. Hijmans J. D. and Shearn D. B. (1965) Partial deletion of short arms of chromosome no. 5. Am. J. Dis. Child. 109, 85-89. Hirschhorn K. and Cooper H. L. (196 1) Apparent deletion of short arms of one chromosome (4 or 5) in a child with defects of midline fusion. Hum. Chrom, Newsletter 4, 14. Hirschhorn K., Cooper H. L. and Firschein I. L. (1965) Deletion of short arms of chromosome 4-5 in a child with defects of midline fusion. Humangenetik 1,479-482. Howard R. 0. (1972) Ocular abnormalities in the cri-du-chat syndrome. Am. J. Dis. Child. 73,949-954. Hustinx T . W. and Wiffels J. C. H. M. (1965) ‘Cri du chat’ syndrome. Lancet 2, 135- 136. Lejeune J., Lafourcade J., Berger R. et al. (1963) Trois cas de deletion partielle du bras court d’un chromosome 5. Acad. Sci. Parts 257,3098-3 102. Lejeune J., Lafourcade J., deGrouchy J. et al. (1964) Deletion partielle du bras court du chromosome 5. Individualisation d’un nouvel etat morbide. Sem. Hc?p. Parts 40, 106%1071.
320
Journal of Dentistry, Vol. ~/NO. 4
McCracken J. S. and Gordon R. R. (1965) ‘Cri du Chat’ syndrome, a new clinical and cytogenetic entity. Lancer 1,23-25. Macintyre M. N., Staples W. I., LaPolla J. et al. (1964) The ‘catcry’ syndrome. Am. J. Dis. Child. 108, 5388542.
Mennicken U., Pfeiffer R., Puhn U. et al. (1968) Klinische und cytogenetische Befunde von 7 patenten mit Cri-du-Chat Syndrome. 2. Kinderheilkd. 114,278-281. Micheau C. and Schlumberger J. R. (1968) Etude anatomopatholoque du larynx dans la maladie du cri du chat. Ann. Pediat. 15, 748. Miller 0. J., Warburton D. and Breg W. R. (1969a) Deletions of group B chromosomes. Proc. first conf. on clin. delineation of Birth Defects. Part V. Phenotypic Aspects of Chromosomal Aberrations. ed. Bergma D in Birth Defects. Orginal Article Series. Vol V 5.100 (1969). Miller D. A., Warburton D. and Miller 0. J. (1969b) Clustering in deleted short arm length among 25 cases with a Bp- chromosome. Cytogenetics 8, 109-l 16. Milunsky A. and Chitham R. G. (1966) The Cri du Chat syndr0me.J. Ment. Defic. Res. 10, 153-157. Neuhauser G. and Lother K. (1966) Das Katzenschrei Syndrom. Monatsschr. Kinderheilkd. 114,278-281.
Neuhauser G., Singer H. and Zang K. (1968) Cri du chat syndrom mit chromosomenmosaik 46XY/46XY 5p-. Humangenetik 5,3 15-320. Niebuhr E. (1971) The cat cry syndrome (5p-) in adolescents and adults. J. Ment. Defic. Res. 15,277-291. Olive D., Gilgenkrantz S., Cabrol C. et al. (1968) Maladie du cri du chat (5p-) avec gueule de loup. Pediatrie 23, 795. Platt M. and Holmes L. B. (1971) Hypertonia in older patients with the 5p- syndrome. Lancet 2, 1429.
Polani P. E. (1969)
Autosomal
imbalance
and its syndromes
excluding
Down’s Br. Med.
Bull. 25, 81-93.
Ricci N., Ventimiglia B., Dallapiocalla B. et al. (1965) 1278-1279. Schmid V. and Vischer D. (1967) Cri-du-Chat syndrome.
‘Cri du chat’ syndrome.
Lancet
1,
Case Report. Heluet. Paediat. Acta
22,22.
Schreegans E., Rohmer A., Levy-Silagy J. et al. (1966) Un cas de maladie du cri du chat. Deletion partielle du bras court du chromosome 5. Pediatrie 21, 823. Schroeder H., Schleiermacher E., Schroeder T. et al. (1967) Zur klinischen differential diagnose der Cri du Chat syndroms. Humangenetik 4, 294-304. Scully C. (1973) Down’s Syndrome. Br. J. Hosp. Med. 10, 186-l 96. Sedan0 H. O., Look R. A., Carter C. et al. (1971) B group short-arm deletion syndromes. Birth Defects. Orginal Article Series. VII. 89-97. Taylor A. I. (1967) Patau’s, Edward’s and cri du chat syndromes: a tabulated summary of current findings. Develop. Med. Child. Neural. 9, 76-86. Taylor J. H. (1969) In: Caspari E. W. and Ravin A. W. (ed.) Genetic Urganisation. VoZ 1. New York, Academic Press, p. 163. Valentine G. M. (1969) The Chromosome Disorders. 2nd ed. London, Heinemann. Warburton D. and Miller 0. J. (1967) Dermatoglyphic features of patients with a partial short arm deletion of a B group chromosome. Ann. Human Genet. 31, 189-208. Wolf U., Reinwein H., Porsch R. et al. (1965) Defizienz an den kurzen Armen eines chromosomes Nr 4. Humangenetik 1,397-413. Zellweger H. (1966) Cri du chat with chromosomal mosaicism. Lancet 2, 57.
