Toriello Carey syndrome - Wiley Online Library

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TORIELLO CAREY SYNDROME: CASE REPORT

ARTICLE ABSTRACT Toriello Carey syndrome is a rare recessive autosomal disease whose clinical manifestations are more evident in males. Some authors report that the general characteristics of this disease are agenesis of the corpus callosum, mental disability, convulsions, atrial septal defect, pulmonary artery stenosis, pyloric stenosis, and hypospadias. Facial and cranial alterations may occur, including hypertelorism, telecanthus, divergent strabismus, malformed ears, anteverted nares, retrognathism, and cleft palate. This paper reports on a 13-year-old male with Toriello Carey syndrome and leucoderma, and describes his oral problems and his dental care.

KEY WORDS:

Toriello Carey, agenesis of the corpus callosum, mental retardation

Toriello Carey syndrome: genetic, clinical, and oral considerations: a case report Márcia Bueno de Carvalho Maretti, DDS;1 Aida Sabbagh Haddad, PhD;1 Maria Cristina Duarte Ferreira;2 Renata de Oliveira Guaré, PhD;3* Luís Garcia Alonso, PhD4 1Persons

with Disabilities Division, ABENO (Associação Brasileira de Ensino Odontológico), Brasil; student, Post Graduation student, Universidade Cruzeiro do Sul (UNICSUL), Brasil; 3The Discipline of Dentistry, Persons with Disabilities Division, Post Graduation Professor, Universidade Cruzeiro do Sul (UNICSUL), Brasil; 4Morphology and Genetic Department, Universidade Federal de São Paulo-Escola Paulista de Medicina, Brasil. *Corresponding author e-mail: [email protected] 2PhD

Spec Care Dentist 31(2): 68-72, 2011

Introduction Toriello Carey syndrome (OMIM 217980) was first described by Toriello Carey1 in 1988, in four children of both sexes. Three of the four were siblings, suggesting an autosomal recessive inheritance for this syndrome. Even though some authors2–7 believe that the syndrome is influenced by gender, the autosomal recessive model is most widely accepted and should be considered in genetic counseling. Toriello et al.8 described the first case, in which the diagnosis was made in the 22nd week of gestation by morphological ultrasound techniques, showing that the syndrome can be detected early where a family history exists. The most recent case history was described by Martin-Denavit et al.,9 who reported on a patient with Toriello Carey syndrome associated with an unbalanced reciprocal translocation in chromosomes 8 and 18 (46,XY,t[8;18][p12;q22]). This finding was confirmed by molecular cytogenetic techniques on the father of the child, who was cytogenetically balanced and carried a structural chromosome aberration. Clinical manifestations seem to be more evident in males, in whom mental disability ranges from moderate to severe; while in females, mental disability ranges from light to moderate.3 Barisic et al.10 suggested that mental disability was not present in all cases, based on the findings of two subjects in five families.

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The differential diagnosis of Toriello Carey syndrome includes Pierre Robin Malformation Sequence (OMIM 261800), which was suggested by Toriello Carey,1 Cåmara et al.,11 Jespers et al.,12 and Aftimos and McGaughran,6 and Opitz syndrome (OMIM 300000) has also been suggested by Jespers et al.12 and Aftimos and McGaughran.6 Toriello et al.8 did an extensive review of the published literature and likely new cases of Toriello Carey syndrome, which totaled 45 patients, whose ages varied from 1 to 14 years. Of these subjects, 27 were males (two were monozygotic twins), 17 were females, and with 1 the unknown gender (it was an early diagnosis reported by Palandi et al.7). Of these 45 patients, 16 had died (11 were males aged from 1 day to 6 years old, while 5 were females aged from 19 days to 14 years). Most of the children presented with normal weight, length, and head perimeter at birth, with only seven children below average, yet many of them failed to grow properly after birth.

©2011 Special Care Dentistry Association and Wiley Periodicals, Inc. doi: 10.1111/j.1754-4505.2011.00179.x

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Most of the children eventually developed microcephaly, although it was likely that the size of the head was proportional to the size of the body. One child eventually developed hydrocephaly. Thirty-seven of the 45 patients studied8 had involvement of the corpus callosum, a cardinal sign of the syndrome. In 19, the corpus callosum was absent, 10 had hypoplasia, and 8 had partial agenesis. Six children presented with cerebral atrophy to certain extent and only two children had a normal brain image. Mental disability was observed in all the children to varying degrees. Cranial anomaly was a common finding and the eye structures were usually normal. All 45 patients in that study8 were diagnosed with telecanthus, hypertelorism, and/or short palpebral fissures. The nose was described as short or small in 40 subjects. Congenital defects are anomalies in structure, function, or metabolism of an organism and their causes may be genetic or environmental. Lip and palate fissures are isolated congenital defects whose etiology is multifactorial. Cleft lip and palate is the most frequent congenital malformation of the face and it is important to teach caregivers how to correctly feed these children and how to maintain oral hygiene. In the 45 cases reported by Toriello et al.,8 only three subjects did not have palatal involvement and micrognathism. However, Pierre Robin sequence was found in 40 of the children. No ear anomalies were detected in two children. A short neck with excess skin was observed in 32 children. All the children had laryngeal or tracheal anomalies. Cardiovascular anomalies were found in 33 children. The musculoskeletal system of 19 children had anomalies in shape and number. Brachydactyly of the hands and clinodactyly of the fifth finger of the hands were common findings. The authors concluded that typical manifestations were present in more than 50% of the subjects. Thus, whenever Toriello Carey syndrome is suspected, chromosomal analysis and prenatal diagnosis should be done, in addition to a detailed physical examination, in order to detect heart defects and malformations of the corpus callosum.

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The general morphological phenotype of this syndrome according to numerous authors3,4–6,8,13–15 include short neck with excess skin, partial or total agenesis of the corpus callosum, cortical atrophy, limb anomalies, mental disability, and convulsions. Heart defects, pulmonary stenosis (artery and valve), laryngeal and pharyngeal anomalies, pyloric stenosis, hypospadias, generalized hypotonia, stunted growth, small hands, absence or hypoplasia of the clavicles, thoracic asymmetry, and extra ribs may also be present. Craniofacial changes mentioned by these authors3,4–6,8,13–15 include microcephaly, wide fontanelle, hydrocephaly, small palpebral fissures, short eyelashes, ocular hypertelorism, telecanthus, divergent strabismus, prominent and low-set ears, small nose with small and anteverted nares, microstomia, microretrognathism, glossoptosis, cleft palate, oligodontia, and malocclusion.

Case repor t This case reports a 13-year-old Caucasian male, who was referred to the clinic of the Dental Specialization Course for Patients with Special Needs by a pediatric physician. The mother reported that this had been her first pregnancy and that at that time she was a healthy 18-year-old girl and that the father was a nonblood related, healthy 17 year old. Prenatal care began at 2 months gestation, and the mother reported that during the 3rd month, premature amniorrhexis occurred. An ultrasound was requested and her pregnancy was labeled as high risk. The child was born by an uneventful, routine, vaginal, full-term delivery. Forceps were not used. The child weighed 2600 g, and was measured at 44 cm in length. The baby’s head circumference was 34 cm and he had Apgar scores of 4 and 6 at the 1st and 5th minutes, respectively, after birth. The child did not cry. External abnormalities were visible at birth. The child remained in the hospital for 5 days after birth due to respiratory difficulties, but this was not initially reported by the mother because she did not know the importance of the

need to have more evaluations to determine a diagnosis. The child began breastfeeding on the 5th day after birth until 1 month after birth, when breastfeeding was stopped and a bottle was substituted with a nipple that had a large hole. The breastfeeding was stopped because the mother told us that the child had difficulty sucking, and also an esophageal stenosis had been diagnosed. The patient at the time of examination had a healthy 2-year-old younger sister with no disabilities. The mother reported that the patient had viral meningitis at 3 months of age. At 9 months, peripheral blood karyotyping revealed 46,XY(30) in metaphase investigated by G-band staining with a resolution of 400 bands. At 1 year and 7 months, the child was referred for a clinical genetics assessment and, through systematic research of specific computer programs, the diagnosis of Toriello Carey syndrome16 was suggested. At 2 years of age, he had anemia, pneumonia, hepatitis, also pyloric stenosis was diagnosed, and he had antireflux and hiatal hernia surgery. The child had a history of excessive gastroesophageal reflux, leading to regurgitation of milk when feeding from a bottle. He had episodes of gagging, excessive crying, sleep interruption, with a predisposition to infections and respiratory disorders. Until 2 years of age, the child had been prescribed phenobarbital due to a history of seizures. Phenobarbital is an anticonvulsant, hypnotic, and sedative drug, from a class of barbiturates, which features intense anticonvulsant or antiepileptic agents with minimal effect on the state of alertness. It interferes with gamma-aminobutyric acid receptors, blocking nerve impulse transmission in the central nervous system (CNS), which reduces motor activity and raises the seizure threshold. At the time of examination, the characteristics observed in the clinical genetics and complementary examinations included partial agenesis of the corpus callosum, mental disability, severe stunting (at 13 years of age, the child was the size of a 4 year old), brachydactyly,

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and alterations in hearing, sight, speech, motor coordination and locomotion. Furthermore, the patient had a heart murmur with no hemodynamic abnormality and he also was anally incontinent. The craniofacial and oral changes were wide anterior and posterior fontanelles, prominent and low-set ears, and small nose with anteverted nares, telecanthus, ocular hypertelorism, retrognathism, and hypotonic facial and labial muscles, which resulted in mouth breathing (Figure 1). The intraoral characteristics included agenesis of the lower-left permanent second premolar, verified by a panoramic radiograph, lower-anterior dental crowding, and Angle Class I anterior open bite. The eruption pattern of the teeth was compatible with the child’s chronological age (Figures 2 & 3). Currently, the child had not been prescribed any medication, but was allergic to metamizole sodium. He had maintained the habit of sucking his fingers and frequently places four fingers of the same hand inside his mouth, which had caused calluses on his fingers (Figure 4). The patient could chew and swallow, but could not feed himself or perform any other activities of daily living on his own. The mother stated that the child did not enjoy chewing and preferred soft and liquid foods. Given the individual needs of this patient, a treatment plan that emphasized prevention, education, and family motivation was developed. The mother was given instructions on how to feed the patient as well as how to maintain oral hygiene at an adequate level. The mother was advised to wrap a piece of cloth or surgical tape on the boy’s hands and fingers to inhibit sucking, but this did not work. Written-informed consent was obtained from his family after all treatment procedures had been fully explained. The mother was always with the child during dental treatment. She helped to restrain the child by sitting with the child between her legs and holding him. In addition to this, a rubber mouth prop was used to keep the child’s


Figure 1. Facial characteristics of the 13-year-old patient. Observe the facial and labial hypotonia.

Figure 2. Occlusal view of the maxillary arch, showing the primary and permanent teeth.

mouth open and a saliva ejector was used during treatment. During the first phase of treatment, a panoramic radiograph was made to determine the condition of the dentition. Temporary restorations of glass ionomer were placed in the occlusal surfaces of the following teeth: maxillary right primary first molar, left

primary first molar, and mandibular left primary second molar, left primary first molar, right primary second molar. Next, the following teeth: maxillary right permanent first molar, and mandibular left permanent first molar, right permanent first molar, as well as the maxillary right primary second molar, and mandibular right primary

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Figure 3. Panoramic radiograph showing agenesis of the lower left permanent second premolar. Figure 5. The patient continued habit of sucking his fingers.

Figure 4. The patient had a habit of sucking his fingers, which caused calluses on the fingers.

first molar, were restored with resin and then had a topical application of fluoride varnish and sealant. Since the patient was at high risk17 for caries, we suggested that he return every 3 months for maintenance of his oral health and to help motivate the family to care for him. However, the family only brought him in for maintenance care every 6 months, at which time he received topical application of fluoride varnish to control dental caries. Unfortunately, the

M a re t t i e t a l .

last return appointment for this patient was in 2008 when he was aged 14 and he died during the next year.

Discussion The patient reported in this case history had nearly all of the characteristics mentioned except for cleft palate, micrognathism, and structural heart disease with hemodynamic abnormalities. This shows the variable expression of this syndrome and a more benign nature

of this phenotype, which allowed the patient to survive into his teens. This patient was the fifth reported person with the syndrome not to have a cleft palate. It has also been reported by Barisic et al.10 and Czarnecki et al.,3 who observed the absence of cleft palate in four of 45 patients diagnosed with this syndrome. Toriello et al.8 reported that micrognathism was absent in five of the 45 children they studied and heart disease was absent in 33 of the 45 children, which is 73.3%. Premature death occurred in the 45 subjects cited by Toriello et al.8; only one 14-year-old patient was still alive. The patient described in this case report was a 13-year-old boy, so at the time we saw him, he was probably the second oldest surviving patient with the syndrome. This child had the habit of sucking his fingers. He also had facial and labial hypotonia, dental crowding in the mandibular-anterior region, and an Angle Class I anterior open bite. These characteristics and the agenesis of the mandibular left-permanent second premolar have not been previously reported

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in the literature. Dental agenesis is common as an isolated characteristic, but we cannot discard the possibility that this may be one more phenotypic deviation of this syndrome. Therefore, we suggest that a careful medical and dental history and intraoral clinical examination should be routinely done when screening and investigating individuals with malformation syndromes. When comparing this patient with those cited in the literature,1–15 we concluded that this is the 46th case of Toriello Carey syndrome: 19 of them have been reported in publications and 26 were mentioned for the first time by Toriello et al.8

Conclusions It is important for dental personnel to know the general and oral aspects of Toriello Carey syndrome in order to treat the caries, periodontal disease, and malocclusions seen in these patients and so become part of a multidisciplinary team who will care for the health of these patients.

References 1.

Toriello HV, Carey JC. Corpus callosum agenesis, facial anomalies, Robin Sequence,


and other anomalies: a new autosomal recessive syndrome? Am J Med Genet 1988;31:17-23. 2. Lacombe D, Creusot G, Battin J. New case of Toriello-Carey syndrome. Am J of Med Genet 1992;42:374-6. 3. Czarnecki P, Lacombe D, Weiss L. TorielloCarey Syndrome: evidence for x-linked inheritance. Am J Med Genet 1996;65:291-4. 4. Till M, Bourgeois J, Plauchu H. TorielloCarey Syndrome. Am J Med Genet 1997;70:332. 5. Ohta H, Masuno M, Kimura J, et al. Toriello-Carey Syndrome with endocardial fibroelastosis. Am J Med Genet 1999;87:271-2. 6. Aftimos S, McGaughran J. Toriello-Carey syndrome: case report with additional findings. Am J Med Genet 2001;98:273-6. 7. Paladini D, Russo MG, Tartaglione A, et al. Prenatal ultrasound diagnosis of TorielloCarey syndrome. Prenat Diagn 2002;22:1185-7. 8. Toriello HV, Careu JC, Addor MC, et al. Toriello-Carey syndrome: delineation and review. Am J Med Genet 2003;123A:84-90. 9. Martin-Denavit T, Till M, Plauchu H. Toriello-Carey Syndrome and unbalanced translocation t(8;18)(p12;q22). Am J Med Genet 2004;128A:219-21. 10. Barisic I, Peter B, Mikecin L. Further delineation of the Toriello-Carey syndrome: a

11.

12.

13.

14.

15.

16.

17.

report of two siblings. Am J Med Genet 2003;116A:188-91. Camera G, Righi E, Romagnoli G. TorielloCarey syndrome: report of a new case. Clin Dysmorphol 1993;2:260-3. Jespers A, Buntinx I, Melis K, et al. Two siblings with midline field defects and Hirschspring Disease: variable expression of Toriello-Carey or new syndrome? Am J Med Genet 1993;47:299-302. Chinen Y, Tohma T, Izumikawa Y, et al. Two sisters with Toriello-Carey syndrome. Am J Med Genet 1999;87:262-4. Wegner KJ, Hersh JA. Toriello-Carey syndrome: an additional case and summary of previously reported cases. Clin Dysmorphol 2001;10(2):145-8. Kataoka TR, Ito A, Nakabori T, et al. Toriello-Carey syndrome associated with respiratory failure and nonmechanical ileus. Am J Med Genet 2003;120A:537-41. Winter RM, Baraitser M. London dysmorphology database [computer program], Version 2.2.0. London, UK: Polyhedron Software Ltd; 1999. American Academy of Pediatric Dentistry. Policy on use of a caries-risk assessment tool (CAT) for infants, children and adolescents. Available at: http://www.aapd.org/media/ policies_guidelines/p_cariesriskassess.pdf. [Accessed on December 8, 2010].

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