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 Table of Contents  
CASE REPORT
Year : 2018  |  Volume : 30  |  Issue : 1  |  Page : 92-95

Cornelia de-Lange syndrome - A case report


Department of Oral Medicine and Radiology, A. J. Institute of Dental Sciences, Mangalore, India

Date of Submission11-Jan-2017
Date of Acceptance17-Feb-2018
Date of Web Publication23-Apr-2018

Correspondence Address:
Dr. Charvi Chawla
Department of Oral Medicine and Radiology, A. J. Institute of Dental Sciences, Mangalore
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jiaomr.JIAOMR_153_16

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   Abstract 


Cornelia de-Lange syndrome (CdLS) is a rare multisystem developmental disorder characterized by psychomotor retardation and delayed growth associated with a series of malformations, including facial dysmorphia, upper-extremity malformations, hirsutism, cardiac defects, and gastrointestinal abnormalities. There is no definitive biochemical or chromosomal marker for the prenatal diagnosis of syndrome so it is important for the clinician to know etiopathological aspects and characteristic features to provide health care and help improve the quality of life of affected individuals.

Keywords: Cornelia de Lange Syndrome, congenital abnormality, dysmorphic features, growth retardation


How to cite this article:
Chawla C, Rao PK, Kini R, Shetty D. Cornelia de-Lange syndrome - A case report. J Indian Acad Oral Med Radiol 2018;30:92-5

How to cite this URL:
Chawla C, Rao PK, Kini R, Shetty D. Cornelia de-Lange syndrome - A case report. J Indian Acad Oral Med Radiol [serial online] 2018 [cited 2019 Nov 17];30:92-5. Available from: http://www.jiaomr.in/text.asp?2018/30/1/92/230888




   Introduction Top


Cornelia de-Lange syndrome (CdLS), also known as Brachmann de-Lange syndrome, is a multisystem syndrome involving congenital malformations, growth retardation, and neurodevelopmental delay.[1] Exact incidence of the condition is unknown, but it is estimated to be 1 in 10,000. There is no racial predilection.[2] Most cases are sporadic, but familial transmission with an autosomal dominant hereditary pattern has also been reported. It was first reported by Dr. Cornelia de lange, a dutch pediatrician in 1933. Brachmann in 1916 had observed similar features with additional feature of deficiencies of upper limb in child with autopsy. For the reason of their contributions, both names have been attached to the name of the syndrome.[3] Here we report a case of CdLS with characteristic facial features and physical findings.


   Case Report Top


A 21-year-old male patient came to the dental OPD for correction of malocclusion. On taking the history, it was known that he was a full-term baby born (G3P2A1L2) mother by normal uterine delivery (NUD) and after delivery the baby did not cry. He was kept under observation in neonatal intensive care unit (NICU) for 40 days. During the period of observation, he developed cyanosis and diagnosed to have perimembranous ventricular septal disease (VSD). During the following year child developed a failure to thrive and suffered from recurrent respiratory tract infection, speech, and hearing defect. At the age of 12, he was admitted with compliance of delayed developmental milestones. He was diagnosed to have left facial palsy with lagophthalmos and right severe and left mild hearing loss.

Extraoral examination revealed facial asymmetry with micrognathic mandible and deviation of angle of mouth to right [Figure 1]a and [Figure 1]b, prominent symphysis, increased anteroposterior diameter of skull [Figure 1]c, low hairline, and low set ear [Figure 1]d along with limb abnormalities [Figure 1]e and [Figure 1]f. The mouth was fish like with long philtrum, bushy eye brows with long curled eyelashes.
Figure 1: (a) Facial asymmetry with deviation of mandible towards right side, (b) micrognathic mandible, (c) increased AP diameter of skull, (d)low set ear, (e and f) limb abnormalities

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Intraoral examination revealed high arched palate [Figure 2]. Hard tissue examination revealed generalized crowding, missing teeth in relation to 17, 27, 37, 45, 46; Elli's class 1 fracture in relation to 11 and dentinal caries in relation to 36 and 47.
Figure 2: High arched palate

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Radiographic examination included orthopantomogram, lateral cephalogram, and hand wrist X-ray. Orthopantomogram revealed partial anodontia [Figure 3]a. Cephalogram revealed protruded maxillary incisors, horizontal growth pattern, and delayed growth spurt [Figure 3]b. Hand and wrist X-ray revealed short first metacarpal, clinodactyly of fingers, and hypoplastic appearance of epiphyseal center in relation to ulna [Figure 3]c.
Figure 3: (a) OPG reveals partial anodontia, (b) Cephalogram revealed protruded maxillary incisors, horizontal growth pattern and delayed growth spurt, (c) Hand and wrist xray revealed short first metacarpal, clinodactyly of fingers and hypoplastic appearance of epiphyseal centre in relation to ulna

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   Discussion Top


CdLS is a complex congenital anomaly or mental retardation disorder with unknown etiology. No age, racial, or gender predilection has been reported. The estimation of overall prevalence is difficult because of unknown proportion of milder cases; however, it occurs one in every 10,000 live births, and approximately one third of them are delivered prematurely. The diagnosis is primarily clinical and is based on signs and symptoms of a distinct phenotype, mainly in the face and limbs.[4] The duplication or partial trisomy of chromosome 3q26-27 has been pointed out as a probable cause and is seen in few cases whereas previous study suggested that the etiology is related to mutations in the Nipped-B-Like (NIPBL) gene which has been identified in 26% to 56% of cases.[5]

The symptoms are very vast affecting the entire body affecting cardiac, skeletal, gastrointestinal, vision, and auditory systems. Facial features are the hallmark of the syndrome which includes microbrachycephaly, high forehead, short neck, bushy eyebrows, long curled eyelashes, ptosis, strabismus, small nose, anteverted nostrils, thin upper lip, fish like mouth, long philtrum, cleft palate, micrognathic mandible, prominent symphysis, and spurs in the anterior angle of the mandible. Oral manifestations include cleft palate, macroglossia, microdontia, partial anodontia, and delayed tooth eruption.[6],[7] Skeletal features include short stature, clinodactyly of toes and fingers, hirsutism, and proximally placed thumbs. Gastrointestinal problems mainly include gastroesophageal reflux disease (GERD), vomiting, belching, heartburn, or intermittent poor appetite. Vision problems include nystagmus, strabismus, ptosis, or myopia. Auditory defect includes mild to moderate or even severe hearing loss. They have narrow ear canals leading to problem with chronic ear drainage. Cardiac defect includes congenital heart disease, most common being ventricular septal defect. Mental issue are common with average IQ score being 53 which is within the mild to moderate range of mental retardation though ability to communicate is hindered exhibiting errors in articulation, with sound substitutions and distorted or missing consonants. Other less frequent findings are seizures, hyperactivity, irritability, sleep disturbances, and self-injurious behaviors. The presence of severe subnormalities has usually been a major factor in making this diagnosis.[8],[9]

Van allen et al. proposed a classification system. Type 1 “classic” patients have the characteristic facial and skeletal changes. Type 2 “mild” patients have similar facial and minor skeletal abnormalities that were noted in type 1; however, these changes may develop later or may be partially expressed. Type 3 “phenocopies” includes the patients who have phenotypic manifestations, which are casually related to chromosomal aneuploidies or teratogenic exposures.[10]

The patient history in CdLS provides relevant clues to the diagnosis, such as the course of pregnancy and delivery. Preterm delivery is noted in 30% cases. Initial diagnosis can be made through ultrasound between 20 weeks and 25 weeks of gestation. The most obvious abnormality visualized is the missing or abnormally short upper limb. 3-D ultrasound examination is performed which reveals long eyelashes, hypertrichosis, low set ears, and micrognathia where small jaw interferes with the infants feeding.[11] Diagnostic criteria for CdLS was formulated by the CdLS Foundation.[12] If molecular testing has identified a mutation in one of the associated genes, the individual has CdLS. Otherwise; clinical findings should meet facial criteria, as well as criteria for two to three of six other system categories. At least one of the involved systems should be in the areas of growth, development, or behavior [Table 1] and [Table 2].
Table 1: Major criteria

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Table 2: Minor criteria

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Management of such patients is done by team approach including dental surgeon, cardiologist, gastroenterologist, endocrinologist, urologist, and ENT specialist. Family support is also essential, especially at the time of diagnosis. It is important to provide the family with information on the syndrome, which could help parents to cope emotionally and cooperate with regard to the child's treatment.[13]


   Conclusion Top


The occurrence of CdLS places serious limitations on the lives of affected individuals. The prognosis for patients with mild form is much better than that for patients with the classic form. Children often suffer psychological lag and developmental delay so a multidisciplinary approach to caring for patients with CdLS is essential.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
   References Top

1.
Bhuyian ZA, Zilfalil BA, Hennekam RC. A malay boy with the cornelia de lange syndrome: Clinical and molecular findings. Singapore Med J 2006;47:724-7.  Back to cited text no. 1
    
2.
Beck B, Fenger K. Mortality, pathological findings and causes of death in de- lange syndrome. Acta Paediatr Scand 1985;74:765-9.  Back to cited text no. 2
[PUBMED]    
3.
DeScipio C, Kaur M, Yaeger D, Innis JW, Spinner NB, Jackson LG, et al. Chromosome rearrangements in cornelia de Lange syndrome (CdLS): Report of a der (3) t (3; 12)(p25. 3; p13. 3) in two half sibs with features of CdLS and review of reported CdLS cases with chromosome rearrangements. Am J Med Genet A 2005;137:276-82.  Back to cited text no. 3
    
4.
Guadagni MG, Cetrullo N, Piana G. Cornelia de lange syndrome: Description of the orofacial features and case report. Eur J Paediatr Dent 2008;9:9-13.  Back to cited text no. 4
[PUBMED]    
5.
Gillis LA, McCallum J, Kaur M, DeScipio C, Yaeger D, Mariani A, et al. NIPBL mutational analysis in 120 individuals with Cornelia de Lange syndrome and evaluation of genotype-phenotype correlations. Am J Hum Genet 2004;75:610-23.  Back to cited text no. 5
[PUBMED]    
6.
Tayebi N. Cornelia de lange syndrome. Indian J Hum Genet 2008;14:23.  Back to cited text no. 6
[PUBMED]  [Full text]  
7.
Muhammed K, Safia B. Cornelia de Lange syndrome. Indian J Dermatol Venereol Leprol 2003;69:229.  Back to cited text no. 7
[PUBMED]    
8.
Toker AS, AY S, Yeler H, Sezgin I. Dental Findings in Cornelia De Lange Syndrome. Yonsei Med J 2009;50:289-92.  Back to cited text no. 8
[PUBMED]    
9.
Gupta D, Goyal S. Cornelia de-Lange syndrome. J Indian Soc Predod Prev Dent 2005;23:38-41.  Back to cited text no. 9
    
10.
Van Allen MI, Filippi G, Siegel Bartelt J, Yong SL, McGillivray B, Zuker RM, et al. Clinical variability within Brachmann de Lange syndrome: A proposed classification system. Am J Med Genet 1993;47:947-58.  Back to cited text no. 10
    
11.
Urban M, Hartung J. Ultrasonographic and clinical appearance of a 22- week- old fetus with Brachmann-De Lange syndrome. Am J Med Genet 2001;102:73-5.  Back to cited text no. 11
[PUBMED]    
12.
CdLS Foundation. Cornelia de Lange Syndrome Foundation, Inc.  Back to cited text no. 12
    
13.
Kline AD, Krantz ID, Sommer A, Jackson LV, Levin AV, FlitzPatrick DR, et al. Cornelia de lange syndrome: Clinical review, diagnostic and scoring systems, and anticipatory guidance. Am J Med Genet 2007;143:1287-96.  Back to cited text no. 13
    


    Figures

  [Figure 1], [Figure 2], [Figure 3]
 
 
    Tables

  [Table 1], [Table 2]



 

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