Jakarta, Indonesia

CRANIOFACIAL Incomplete Cleft Palate in Cornelia de Lange Syndrome Fory Fortuna, Prasetyanugraheni Kreshanti, Siti Handayani, Kristaninta Bangun Jakarta, Indonesia Background: Cornelia de Lange Syndrome (CdLS) is a rare congenital anomaly inheritance syndrome. The prevalence is 1.6-2.2/100.000 of 8,558,346 births in Europe. Cleft palate is less frequent malformation of this syndrome (21,7%) than other associated malformations. The diagnosis can be obtained clinically based on CdLS diagnostic criteria by USA CdLS Foundation. This is the first case in our hospital. Patient and Method: A case of a 4-year-old girl who came to our attention at Cleft and Craniofacial Center Cipto Mangunkusumo National General Hospital for incomplete cleft palate. Parents’ major concerns was feeding problem. The clinical investigations showed that the child met diagnostic criteria for CdLS as described in literatures. We manage this case in collaboration with paediatric department and other related specialists, including radiologist and craniofacial orthodontist. We performed Veau-Wardill-Kilner’s palataoplasty for the incomplete cleft palate. Paediatric department arranged provision of dietary. Result: This patient with incomplete cleft palate whom we treated by palatoplasty was moderately involved by CdLS (severity score 17). After 3 weeks follow-up, we have overcome feeding problem and body weight gained. Summary: Patient with CdLS needs early multidisciplinary team approach management for maximum outcome, because variety of associated malformations may present and life-threatening. Diagnostic criteria by USA CdLS Foundation assist health care personnel recognize this syndrome early. Keywords: CdLS, multidisciplinary team approach, incomplete palatoschisis, syndromic Latar Belakang: Sindrom Cornelia de Lange (CdLS) adalah sindrom kongenital yang jarang terjadi. Angka prevalensi sekitar 1.6-2.2/100.000 dari 8,558,346 kelahiran in Eropa. Celah langit-langit adalah malformasi yang paling jarang terjadi (21,7%) dibandingkan dengan malformasi lain. Diagnosis dapat ditegakkan secara klinis berdasarkan kriteria diagnosis yang dibuat oleh yayasan CdLS di Amerika Serikat. Ini adalah kasus pertama di rumah sakit kami. Pasien dan Metode: Kasus pasien anak perempuan umur 4 tahun yang datang ke Cleft and Craniofacial Center Rumah Sakit Umum Pusat Cipto Mangunkusumo dengan masalah celah langit-langit inkomplit. Keluhan utama orang tua adalah masalah makan dan minum. Hasil pemeriksaan klinis terhadap pasien ini mengarah pada kriteria diagnostik CdLS sesuai literatur. Kami mengelola kasus ini bekerja sama dengan dengan Departemen Ilmu Kesehatan Anak, dan spesialis terkait, diantaranya spesialis radiologi dan spesialis ortodonti kraniofasial. Kami melakukan palatoplasti dengan teknik Veau-Wardill-Kilner. Hasil: Pasien dengan celah langit-langit yang kami lakukan palatoplasty memiliki kriteria diagnosis CdLS sedang (skor 17). Setelah follow up selama 3 minggu, masalah makan dan minum telah teratasi dan peningkatan berat badan. Ringkasan: Pasien dengan CdLS membutuhkan manajemen pendekatan awal tim multidisiplin karena mungkin saja terdapat malformasi yang dapat mengancam jiwa. Kriteria diagnosis oleh yayasan CdLS Amerika Serikat sangat membantu petugas kesehatan mengenali sindrom ini lebih dini. Kata Kunci:.CdLS, multidisciplinary team approach, incomplete palatoschisis, syndromic Received: 30 May 2012, Revised: 15 July 2012, Accepted: 2 January 2013. (Jur.Plast.Rekons. 2013;1:21-7) ornelia de Lange Syndrome (CdLS) was first described by Cornelia de Lange, a Dutch paediatrician in 1933.1,2 This syndrome is also called as Brachmann de Lange syndrome (BdLS) since he reported a patient with similar characteristics at autopsy in 1916.1,2,3,4 It is slightly more common in woman than man (W/M=1,3/1).1 There is no racial tendency.1,2 Based on 23 years of epidemiologic monitoring (8,558,346 births in the 1980-2002 C From the Division of Plastic Reconstructive, and Aesthetic Surgery University of Indonesia Cipto Mangunkusumo Hospital, Jakarta, Indonesia. Presented in 16th IAPS Scientific Meetings In Sibolangit, Medan, North Sumatra, Indonesia period), the prevalence of the classical form of CdLS to be 1.24/100,000 births or 1:81,000 births and estimated the overall CdLS prevalence at 1.6-2.2/100,000 in Europe.5 The most frequent associated congenital malformations were limb defects (73.1%), congenital heart defects (45.6%), central nervous system malformations (40.2%), and cleft palate (21.7%).5 First week survival of live born infants with CdLS is quite high (91.4%). Evidence showed that almost 70% of Disclosure: The authors have no financial interest to declare in relation to the content of this article. www.JPRJournal.com 21 Jurnal Plastik Rekonstruksi - January - March 2013 Table(1..Scoring.System.for.Severity.in.CdLS... Parameter 1 Point 3 points 5 points Birth weight Above 2,500 g 2,000-2,500 g Below 2,000 g Sitting alone Before 9 months 9-20 months Over 20 months Walking alone Before 18 months 18-42 months Over 42 months Saying first word Before 24 months 24-48 months Over 48 months Upper limb malformation No defect Partial defect (more than two digits) Severe defect (less than two digits) Number of other major malformations 0-1 2-3 More than 3 Hearing loss Absent Mild Moderate-Severe Scoring: >22 Points, severely involved;15-22 points, moderately involved; <15 points, mildly involved. Ages based on Kline et al. [1993b] using 25th-75th centiles of completing milestones. (based in part on Kline et al, 1996) patients, born after the 37th week of gestation, weighed <or=2,500 g. Severe limb anomalies were more often present in males.5 The etiology of this syndrome is still not clear.6 Mutations in autosomal dominant inheritance of Nipped-B homolog (NIPBL) and SMC3-related CdLS also the x-linked inheritance of SMC1A-related CdLS have been suggested as probable cause of this syndrome.6,7,8 The characteristic of CdLS are generally divided into facial features, major and minor criteria and diagnostic criteria for CdLS were created by the CdLS Foundation’s Medical Director Antonie Kline, M.D. in collaboration with members of the Clinical Advisory Board (CAB) of the CdLS Foundation and the Scientific Advisory Committee of the World CdLS (SAC) Federation (Figure 5). If genetic testing identified a mutation in one of the associated genes, the diagnosis of CdLS can be established. But by the presence of facial findings (eyebrows that meet at the midline, long eyelashes, short nose, anteverted nostrils, long and prominent area between upper lip and nose, broad or depressed nasal bridge, small or square chin, thin lips, downturned corners, high palate and widely spaced or absent teeth) and meet criteria from two major categories (growth, development, or behaviour) the diagnosis be enforced. Or facial findings meet criteria for at least one major categories and two additional categories (major or minor).11 There are also severity scoring available (Table 1). According to Kline et al, management and treatment of CdLS is based on the consensus of CAB and SAC, which focuses on prevention of treatable complications, and optimization of developmental ability. Routine medical 22 evaluation for any abnormality condition is needed and each age group has its own particular issues.9 PATIENT AND METHOD The patient is a 4-year-old female patient was brought by her parents’ initiative to general surgery policlinic Cipto Mangunkusumo National General Hospital on November 2011 with cleft palate since birth. She was the first child in the family, born of a full-term sectiocaesarean delivery with a birth weight of 1500 gr, height of 40 cm and the birth head circumference was not measured. The present weight, height, and head circumference were 9400 gr, 85cm, and 42 cm. Both parents were normal and there was no history of deformity in their pedigree. She was admitted at hospital when she was 16 days old because of the feeding problem she had and then returned home without feeding education to parents and also without any suggestion for feeding problem and the cleft palate. She often choked while drinking by using milk bottle and her weight was not gaining normally. She was sitting alone around the age of 18 months, walking alone in the age of 2 years and saying the first word when she was 12-month-old. She was then suggested to come to Craniofacial Centre Cipto Mangunkusumo National General Hospital. Initially we diagnosed this child with Pierre Robbins Syndrome, based on the cleft palate, small jaw, glossoptosis and global development delay she had. Paediatric department found that this child Volume 2 - Number 1 - Incomplete Cleft in Cornelia de Lange Syndrome A D B C E F Figure( 1..4TyearTold. female. pa5ent. with. Cornelia. de. Lange. Syndrome.. She. has. synophrys,. long. eyelashes,. droopy.eyelid,.short. nose,.broad. and.depressed.nasalTbridge,.small.and. squareTchin,.long. philtrum,.thin.lips. with. downturned. corners. (A,B,C).. Generalized. hirsu5sm. is. present. (D).. She. has. incomplete. cleM. palate. as. minor.criteria.of.CdLS.(F).. had diagnostic criteria for CdLS. She presented s e v e r a l d i s t i n c t i v e f a c i a l fi n d i n g s , developmental and growth delay and some behaviour problem (extreme shyness, withdrawal and hyperactivity). She has synophrys, long eyelashes, droopy eyelid, short nose, broad and depressed nasal-bridge, small and square-chin, long philtrum, thin lips with downturned corners (Figure 1.A, B, C). She has incomplete cleft palate as minor criteria of CdLS (Figure 1.F). The over-length of the philtrum is confirmed by OsiriX™ (Figure 2) and is interpretated by Growth Chart for Nose and Philtrum by Zankl et al (Figure 3). The techniques of measuring the philtrum is by drawing a straight line from the lower nose and then measured perpendicularly (Figure 4).10 Her present weight and height is below 5th percentile for age. Generalized hirsutism is present with low frontal implantation of hair and long skin hair (Figure 1.A, B, C, D, E). There was no anomaly in extremities. According to CdLS diagnostic criteria checklist by CdLS Foundation, USA, she has 4 facial findings, 2 major criteria and 3 minor criteria those are sufficient to diagnose CdLS (Figure 5). Her severity score of CdLS was 15 (moderatelyinvolved) [table 3]. Patient was coming back to our department on February 2012 and the patient was prepared for palatoplasty. Her general health was acceptable without cardiac or respiratory problem. The additional requirement tests (general analytical, radiology of thorax and electrocardiogram) did not show any alterations that might contraindicate the general anesthesia. Under general anesthesia the palatoplasty was done using Veau-WardillKilner’s technique. Paediatric department arranged continue provision of dietary and 23 Jurnal Plastik Rekonstruksi - January - March 2013 Figure(2..Philtrum.measurement.by.OsiriX™:.1,801.cm Figure(3..Philtrum.length.is.interpreted.by.Growth.Charts.for.Philtrum.Length.by.Zankl,.et.al.200210 Figure(4..Illustra5on.of.measurement.technique.for.philtrum.length.by.Zankl.et.al.200210 24 Volume 2 - Number 1 - Incomplete Cleft in Cornelia de Lange Syndrome Coming to a Diagnosis: Positive mutation on CdLS gene testing; OR Minor Criteria Musculoskeletal (>one or more of the following) v Absent arms or forearms v v v Facial Findings and meet criteria from two major categories (growth, development or behaviour); OR Three or more of the following or small hands and feet and/or missing digits with two or more of the following: Facial findings and meet criteria for at least one major categories and two additional categories (major or minor) Curved 5th finger Abnormal palmar crease Dislocated elbow/abnormal elbow extension Facial Features Eyebrows that meet at the midline and > three or more of the following: Short 1st knuckle/proximally placed thumb Long eyelashes Short nose, anteverted nostrils Bunion Partial webbing between 2nd and 3rd toes Scoliosis Chest or sternum deformity Hip dislocation or dysplasia Long, prominent area between upper lip and nose Broad or depressed nasal bridge Small or square chin v Thin lips, downturned corners v High palate Widely spaced or absent teeth Major Criteria Growth (>two or more of the following) v Weight below 5th percentile for age v Height/length below 5th percentile for age v Head circumference below 5th percentile for age Neurosensory/Skin (three or more of the following) v Nearsightedness Major eye malformation or peripapiillary Deafness or hearing loss Seizures Mottled appearance to skin Development (>one or more of the following) v v Droopy eyelid(s) Tear duct malformation or inflammation of eyelid Developmental delays or intellectual disability, with speech more affected than motor skills Excessive body hair Small nipples and/or belly button Other Major Systems (three or more of the following) Learning disabilities Gastrointestinal malformation/malrotation Behavior (>two or more of the following) Attention deficit disorder plus hyperactivity v Obsessive-compulsive characteristics Anxiety Constant roaming Agression Self-injurious behaviour Extreme shyness or withdrawal Autistic like features Diaphragmatic hernia Gastroesophageal reflux Cleft palate or submucous cleft palate Congenital heart disease Micropenis Abnormally placed opening or urethra on penis Undescended testes Renal or urinary tract malformation Figure(5..Anomaly.findings.for. diagnos5c.according.to.CdLS.diagnos5c.criteria.checklist..Adopted. from. Cornelia. de.Lange.Syndrome.Founda5on..Diagnos5c.Criteria.Checklist.for.Cornelia.de.Lange.Syndrome.2010.11 543 25 Jurnal Plastik Rekonstruksi - January - March 2013 Table(3..Pa5ent’s.severity.score.of.CdLS:.17.(moderately.involved) 9. Parameter Data Points Birth weight 1500 g 5 Sitting alone 18 months 3 Walking alone 24 months 3 Saying first word 12 months 1 Upper limb malformation No defect 1 Number of other major malformations Incomplete cleft palate, droopy eyelid, hirsutism 1 Hearing loss Absent 1 Total Score 17 growth monitoring. Seven days after the treatment the patient was scheduled for a visit. First week after surgery chocking occurs sometimes. Three week after surgery we found no complaint in feeding and weight was increased to 10 kg. DISCUSSION CdLS is a rare multiple congenital genetic anomaly. The clinical hallmarks of this syndrome are the facial features.2,9 Diagnosis is based upon phenotypic findings compiled by consensus among some members of the Clinical Advisory Board of CdLS Foundation USA (CAB) and the Scientific Advisory Committee of the World CdLS Federation (SAC).8,11,13 This syndrome affect almost any organ system commonly neurodevelopment, craniofacial, gastrointestinal, and musculoskeletal. Some organ system requires early management protocol during the first day of life like craniofacial structures anomalies can affect the viability of a neonate because of their impact on airway/or swallowing.12 So patients with this syndrome needs an immediate integrated team approached consists of specialist from a wide variety of disciplines, medical ethics, and social work to provide holistic care for maximum outcome.13 The patient in our case had her late first consultation with plastic surgeon at 4 years of age, due to her parents’ concern about feeding problem those were choking when drinking, and her body weight was below the children on her age. Her severity of CdLS was moderate. As Kline et all purposed management and treatment since infancy continued by routine medical 26 evaluation, it is now more arduous to treat this patient with maximum outcome. Our on going plan for this patient are monitoring growth via C d L S - s p e c i fi c g r o w t h c h a r t s , d e n t i s t r y evaluation 6 months, paediatric ophthalmologic evaluation annually, audiology testing every 2-3 years. We also plan for speech therapy. SUMMARY . Patient with CdLS needs early multidisciplinary team approach management for maximum outcome because variety of associated malformations may present that can lead to global developmental delay or even death. By knowing distinctive facial features of this syndrome, health care personnel will be greatly assisted to recognize this syndrome early. Kristaninta Bangun, M.D. Plastic Surgery Division Cipto Mangunkusumo General National Hospital kristaninta@yahoo.com REFERENCE 1. 2. 3. 4. Tayebi N. Cornelia de Lange Syndrome: A Case Report. Indian J Hum Genet. 2008;14(1): 23–26 Carbó JG, Jiménez JL, Prats JG, Molins MS. Cornelia de Lange Syndrome: A Case Report. Med Oral Patol Oral Cir Bucal. 2007;12(6): E445-8. 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