SA MEDICAL JOURNAL 13 FEBRUARY 1982 227 Hypoplasia or absence of the depressor anguli oris muscle and congenital abnormalities, with special reference to the cardiofacial syndrome S. E. LEVIN, N. H. SILVERMAN, S. MILNER Summary An asymmetrical crying facies due to hypoplasia or absence of the depressor anguli oris muscle (DAOM) was observed in 23 infants and children. The cases were divided into two groups. Group 1 consisted of 12 patients who had associated cardiac abnormalities. In group 2 were 11 patients' who either had other non-cardiac abnormalities (6) or no other abnormalities (5). The associated cardiac anomalies recorded in the literature are reviewed and 2 infants in this series are reported with abnormalities not previously described. The results of chromosomal analysis have generally been found to be normal, although a patient in our series was found to have trisomy E (18). The incidence of hypoplasia of the DAOM in newborn infants in a maternity hospital is assessed and was found to be lower than reported in other studies. It is concluded that a detailed aM careful examination for congenital abnormalities should be carried out on every child with an asymmetrical crying facies. In rhis paper we report on 23 cases of congenital weakness of the DAOM encountered ar a children's hospital and a maternity hospital. The incidence of this syndrome among newborn infants at the maternity hospital has been estimated. A case associated wirh a chromosomal abnormality - trisomy 18, not previously described - will be presented in some detail, and all the cardiac anomalies associated with DAOM weakness will be reviewed, including 2 previously unreported cardiac abnormalities observed in our series. Patients and methods Of 23 infants with weakness of the DAOM, 18 were observed at rhe Transvaal Memorial Hospiral for Children and 5 at its newborn service at the Queen ViclOria Maternity Hospiral. S. Afr. med. J., 61, 227 (1982). Isolared unilareral partial facial paralysis involving rhe mentalis, quadratus labii inferioris and depressor anguli oris muscles had previously been observed in young children,I,2 bur ir was nor until 1966 rhar Cayler J noted the association of this facial abnormality with congenital heart disease. He extended his series over the year lO include 30 cases of the cardiofacial syndrome.4-6 In addition, there were 2 children with facial weakness and heart murmurs not caused by congenital heart disease. Cayler's observations have been confirmed by other workers in the USA,? France,9 the UK,lO,11 Canada 12 and Rhodesia. l ] Recent studies have stressed thar the asymmetrical crying facies caused by congenital hypoplasia or absence of the depressor anguli oris muscle (DAOM) may occur as an isolated anomaly or may be associated with abnormalities involving systems other than the cardiovascular system,12,14-16 Department of Paediatrics, Johannesburg Hospital and University of the Witwatersrand, Johannesburg S. E. LEVIN, M.B. B.CH., D.C.H. (R.c.P. & S.), f.R.C.P.(EDIN.) N. H. SIL VERMAN, M.B. B.CH., F.C.P. (S.A.) (present address: University of California, San Francisco, California, 94143 USA) S. MILNER, M.B. B.CH., F.C.P. (SA) Date received: 15 May 1981. Fig, 1. Asymmetrical crying facies. There is weakness of the DAOM on the right side. 228 SA MEDIESE TYDSKRIF 13 FEBRUARIE 1982 Aparr from a detailed history and physical examination, \\'here indicated, roentgenographic and electrocardiographic rudie were carried our. Further special im'estigations included cardiac catheterization in 4 cases, chromo ome analysis in 3, electromyography in 2 and detailed \'iral rudies in 2. Autopsies were carried out on all 5 children in the series who died. During a 2-year period at the maternity hospital there were 8845 deliveries, and particular attention was paid to the presence or absence of an asymmetrical crying facies as part of the routine physical examination of newborn infants between the 4th and 6th days after birth. The cases \\'ere divided into t\\·o group. Infants with an as ociated cardiac abnormality \\'ere placed in group I and tho e with no ob en'ed congenital cardiac abnormality in group 2. Patient No. Sex F Results Group 1 (Table I) There \\'ere 12 children in this group (5 males and 7 females), of ages ranging from I day to 2 Fars and 11 months. Weakness of the DAOM was observed on the left side in half the cases (Fig. 1). The cardiac abnormalities were confirmed at open-heart surgery or autopsy in 8 of the 12 patients. In addition to the cardiac anomalies, 9 of the 12 patients had abnormalities invoh'ing other system, e.g. keletal, respiratory and gastrointestinal. Patients 6 and 7 had cardiac abnormalities not pre\'iously described in association \\'ith \\'eakne~ of the DA01\L TABLE I. DAOM WEAKNESS AND CARDIAC ABNORMALITIES Side of Special investigations Cardiac DAOM Birth Age first abnormalities or procedures weight (g) weakness seen ASD (secundum) Right Cardiac catheterization, 2585 2 yrs 9 moo and left SVC open-heart surgery VSD (clinical) VSD (clinical) 2 3 M F 2443 2563 1 yr 4 moo 3d Right Left 4 M 2841 1d Left Cardiac catheterization, viral studies (negative), autopsy TGA and VSD 5 F 3068 6 wks Left 6 F 2060 1d Left Chromosomal analysis (46 XX) Autopsy Tricuspid atresia and PDA Dextrocardia (no intrinsic heart abnormality) 7 M NK 2d Left Surgery, autopsy 8 F 2840 3d Right Cardiac catheterization, autopsy (age 8 ' / 2 mo.) Isolated origin of left subclavian artery off left pulmonary artery, right-sided aortic arch and PDA Truncus arteriosus 9 M 3750 8 moo Right 10 M 2443 6 1/ 2 wks Left Electromyography of facial muscles, chromosomal analysis (46 XV) Chromosomal analysis (trisomy E (18», viral studies (negative), autopsy VSD, nodular thickening of pulmonary and aortic valves 11 F 2898 2 yrs 11 moo Right Cardiac catheterization, open-heart surgery ASD, PDA 12 F 3494 6d Right Cardiac catheterization, open-heart surgery Pulmonary atresia, VSD, PDA Probable truncus arteriosus Other abnormalities Right ear lobe attached to neck, slight hypoplasia of right side of mandible, trigger finger 5th left None Infant of diabetic mother Anal atresia, ex omphalos, absent right radius and thumb Cleft palate, absent ears Sacral myelomeningocele, hypoplastic right lung, single umbilical artery Tracheooesophageal fistula Right mentalis muscle smaller than left (on dissection) Absent right radius, hemivertebrae, anal stenosis Horseshoe kidney, single umbilical artery, undescended testes, partial eventration of right diaphragm Absent right kidney, small right femoral epiphysis Azygous lobe of right lung NK = not known: ASD = atrial septal defect; SVC = superior vena cava; TGA - transpositIon of the great arteries: PDA - patent ductus arteriosus: VSD = venlrlcular septal defect SA MEDICAL JOURNAL 13 FEBRUARY 1982 Case 6. A female infant with a birth weight of 2 050 g had a sacral myelomeningocele, weaknes of the DAOM on the left and a single umbilical artery. In addition the heart was situated in the right chest and there were audible systolic and diastolic murmurs. Roentgenograms of the abdomen revealed situs solitus. Death occurred I month later, and autopsy revealed dextroversion of the heart with a hypoplastic right lung. There were no intracardiac abnormalities. It was assumed that the cardiac murmurs were functional in origin and produced by blood flow through a distorted heart. Case 7. A male infant was diagnosed as having a tracheooesophageal fistula at 2 days· of age. In addition, weakness of the DAOM on the left side of the face was noted. He underwent surgery for the oesophageal atresia and died at the age of 6 days after a stormy postoperative course. Autopsy re\·ealed isolated origin of the subclavian artery from the left pulmonary artery (Fig. 2). A right-sided aortic arch was also present. 229 group. One 4-month-old child with a \·iral illness was uspected to have myocarditi . As ociated non-cardiac abnormalities, major and minor, were found in the remaining 5 patients. Chromosomal analysis Normal karyotypes were found in patients 5 and 9 (group 1), while trisomy 18, suspected on clinical examination, was confirmed in patient 10 of group I (see case report belo\\·). Case report. A male infant weighing only 2443 g was delivered 2 weeks after the expected date. He was the 8th child born to a 39-year-old mother and 44-year-old father. No serious illness had occurred during the pregnancy. Cyanosis was noted hortly after birth and he wa transferred from an outlying hospital at the age of 25 days. His weight \\·as 2500 g, length 44 cm and skull circumference 37,2 cm. A number of abnormalitie suggested trisomy 18; there was micrognathia, a highlv arched palate and low-slung ears, the left being adherent to the side of the skull and the right a 'bat ear'. Weakness of the DAOM on the left was seen on crying. There was moderate webbing of the neck with a 10\\· hairline. There were single palmar creases in both hands with fixed flexion deformities of the 2nd, 3rd, 4th and 5th fingers. 'Rockerbottom' feet were also present. The kull was dolichocephalic with a very large patent anterior fontanelle. Examination of the cardiO\·ascular system re\·ealed cardiomegaly with biventricular hypertrophy. A pansystolic murmur was audible at the 4th left interspace with a gallop sound at the apex. The respiratory rate was mildly increased at 52/min and the li\·er was palpable 2 cm below the right costal margin. Other abnormalities were a left inguinal hernia with undescended testes, a prominent coccyx, limited abduction of the hips, a convergent squint and some hypertonia. Serological tests for toxoplasmosis and rubella were negative. Chromosomal analysis confirmed tri omy 18. The infant developed increasing cyanosis with apnoeic spells and died when 44 days old. The principal findings at autopsy were: single umbilical artery, horseshoe kidney, mild eventration of right diaphragm, and a central liver with ~ loose mesentery. Cardiac abnormalities included a large ventricular septal defect (VSD) with nodules on the pulmonary and aortic \·alyes. The foramen O\·ale was patent and the lungs were atelectatic. Electromyography Fig. 2. Front view of the heart with left subclavian artery originating from the left pulmonary artery (curved arrow). The right-sided aortic arch is also demonstrated (straight arrow). Group 2 (Table II) There were II children in this group (6 males and 5 females), . of ages ranging from I day to 16 mqnths. Involvement of the DAOM was observed on the left side in 6 cases and on the right in 5. No congenital abnormalities were detected in 6 of the II infants. Patient 4 was examined only once, at the age of 4 days, after which she was lost to follow-up; although an associated cardiac abnormality might have become evident later, in the absence of further information the patient has been placed in this This was performed in 2 patients - patient 9 in group I and patient 8 in group 2. In patient 9 (group I) the electromyogram (EMG) of the right lower lip showed no evidence of denervation. On movement a low-amplitude (100 - 150 !J. V) pattern was seen and interference. was markedly reduced. Individual motor unit potentials, however, were quite normal in appearance. The EMG ofthe right frontalis and left lower lip showed a normal full interference pattern with the amplitude much greater (350 !J. V). An attempt to stimulate the facial nerve was not successful. In patient 8 (group 2) the EMG showed no denervation or excess irritability of muscles to the left lower lip. On volitional movement there was a mildly reduced pattern with a maximal amplitude of 600 !J. V. The individual potentials were of normal configuration. The right lower lip showed a good and full interference pattern \\·ith maximal amplitude of 800 !J. V. The amplitude of evoked potentials on stimulating the seventh nen·e on the left was therefore much smaller than on the right. Nen·e conduction on both left and right sides was normal and comparable. Incidence of weakness of DAOM During the 2-year period during which particular attention was paid to an asymmetrical crying facies at the Queen Victoria 230 SA MEDIESE TYDSKRIF 13 FEBRUARIE 1982 TABLE 11. DAOM WEAKNESS WITH OR WITHOUT NON-CARDIAC ABNORMALITIES Patient No. Side of DAOM Special investigations weakness or procedures Sex Birth weight (g) Age first seen F NK 16 moo Left 2 3 F M 3608 3000 15 moo 3 moo Left Left 4 5 F M 2950 3239 4d 1 d Left Right 6 F 3523 12 d Right 7 M 3300 4 moo Right 8 M 3068 9 moo Left 9 F NK 4 moo Left 10 M 3310 9 moo Right 11 M 2670 4d Right K nOt nown; IVP --=- Intravenous pyelography. CPK Other abnormalities Remarks Left lower lobe pneumonia Pyrexial convulsion Radiographs, ECG normal Posterior encephalocele (resected), rudimentary right ear Right facial weakness pr~sent at 8 moo DAOM weakness still present at 13 moo Electromyography, viral studies (negative), IVP, radiographs and ECG - normal Radiographs, ECG normal, raised serum CPK Radiographs, ECG - normal Single umbilical artery, congenital urethral valves, sacral sinus, fusion CS and C6 vertebrae Hypospadias, Mother on antimental retardation, epileptic therapy spastic throughout quadriparesis pregnancy ? Myocarditis, viral infection Hypoplasia of toes Re-examination at 19 mo., DAOM and right foot weakness still present Right ear hypoplastic creatinine phosphokinase Marerniry Hospiral, rhere were 8845 deliveries and 5 babies had weakness of rhe DAOM. This represenrs an incidence of 0,57 per 1000 live binhs. Discussion This series again confirms rhar while unilareral weakness of rhe DAOM may occur as an isolared finding ir is more ofren associared wirh one or more congeniral abnormaliries. Cardiac lesions in association with hypoplasia ofDAOM Table II I documenrs rhe cardiac abnormaljries in 85 reponed examples of rhe cardiofacial syndrome (including our 12 cases). A large variery of lesions has been described. Howel'er, 40 ofrhe 85 ca es are accounred for by rhe diagnosric caregories ofVSD, rerralogy of Fallor or pulmonary arresia wirh VSD, and parenr ducrus aneriosus. In our serie 2 anomalies nor previously described hal'e been encounrered - dexrroversion II'irh funcrional sysrolic and diasrolic murmurs and i olared origin of rhe lefr subclavian anery from rhe lefr pulmonary anery." Mosr of rhe reponed cases (including our oll'n) hal'e been seen from a highly selecred popularion. Perlman and Reisner" were rhe firsr II'orkers who artempred a pro pecril'e assessmenr of rhe prel'alence of rhe asymmerrical crying facies among 6360 newborn infanrs. They found 41 examples, giving an incidence of 1 in 155. Similarly, Papadaros eT al. I I> found an incidence of TABLE Ill. CARDIAC LESIONS DESCRIBED IN ASSOCIATION WITH DAOM HYPOPLASIA (85 CASES) Lesion VSD ,",9,111"" No. cases 20 Tetralogy of Fallot 6 !" PA + VSD' PDA",l1 10 1 9 Coarctation of aorta (± other lesions, e.g. VSD, PDA)o.1J.J4 ASD's ASD and other lesions (e.g. VSD, PS or AI, PDAr" PS'"> 6 Hypoplastic RV syndrome,,,·6.11 TA'~!! A-V canal"" TGA,,,·9 6 4 3 4 5 4 4 3 11 Single ventricle complex o.l1 Other cardiac anomalies,"·7.11 2 10t . Our senes. 1: total anomalous pulmonary venous drainage - 1; aortic stenosis - 1: myocarditis - 1: POAbicuspid aortic valve - double aortic arch - 1: left subclavian artery arising from left pulmonary artery 1; dextrocardia (dextroversion) 1; arrhythmia (paroxysmal atrial tachycardia) - 1. PA pulmonary atresia: PDA patent ductus arteriosus: ASD :;;: atrial septal defect: PS .:=.. pulmonary stenosIs: AI = aortiC Incompetence: RV ::;::- right ventricle: TA truncus artertosus: A-V::;::- atrioventricular: TGA :;;: transposition of the great arteries. + InnomInate artery compression - 2 cases. mitral atresia - = = SA MEDICAL JOURNAL 13 FEBRUARY 1982 0,82% among 4530 consecuti\'e births, and in a later study by Alexiou er (/1. 18 the figure wa 0,68%. Wle examined 8845 live neonates O\'er a 2-year period and were able to find only 5 \\'ith unilateral DAOM weakness. The reason for this striking difference is not known. In a much earlier study'Y it was claimed that in most cases facial paresis in the newborn infant is associated with intrapartum pressure on the exposed portion of the facial nen·e. Hepner lY found that 34 of 46 infants had leftsided paresis; all had been in the left occipito-anterior or left transverse positions during deli\·ery. Similarly, Israeli \\"Orkers ' ; al 0 found the incidence to be highest on the left side. It therefore seems likely that obstetric factor played a part in these cases. On the other hand, in the series reported by Papadatos er al. 16 28 of 37 neonate had left-sided weakness and yet obstetric complications appeared to ha\'e been largely ruled out. It \\'ould appear that further studies on newborn populations combined with long-term follow-up are indicated. Furthermore, Alexiou er al. 18 found that 20% of infants with DAOM hypoplasia had congenital malformations while the figure for a control neonatal population was 2,7%.18 In this series 10 patients had an associated unilateral anomaly; this was on the ame side a the weak DAOM in 8 case. Thi observation is in accord with that of Pape and Pickering,12 who first drew attention to this association. Of the 6 patients with no other detectable abnormalities, 5 had asymmetrical crying facies on the left. Thi left-sided predominance was comme'nted on b\' Perlman and Reisner,l; and \\'as also found in the 2 reports from Greece .16.18 While there should not be much clinical difficulty in differentiating weakness of the DAOM from a true facial paralysis, !.i·1 any doubt can be dispelled by electromyography. With facial nerve palsy there is elevated excitability of the facial nerve with diminished voluntary unit activity, fibrillations and sharp \\'aves at rest. In contrast, infants with an affected DAOM ha\'e clear-cut nen'e latency of normal duration, \\'hile the EMG generall\' shows diminished motor unit acti\·ity. This \\'as found in a paediatric neurological clinic by Nelson and Eng ll in 7 patients \\'ith no other abnormalities. No EMGs were carried out in Pape and Pickering's large series. 12 On re\'ie\\' of the literature 20 more patients \\'ith weakness of the DAO,\19.1O.lli.I".:1O ha\'e undergone electromyography or electrical studies, \\'ith findings similar ro those described above. To this may be added 2 of our patients who have shown normal nerve conduction \\'ith electromyographic features typical of a weak DAOM, thus making a total of 29 cases in which this study has been found to be positi\·e. Recently Mo nreaP 1has questioned the reliability of the EMG, because of technical difficulties in obtaining records. However, it is difficult ro refute the finding of 6 different im'estigarors, all of whom describe an identical EMG pattern, \\'hen present, in association w'ith DAOM \\·eakness. MonreaPI also reported 5 patients \\'ith this syndrome (of a total· of 13) who displayed additional peri-oral anomalies on the supposedly normal or strong side. He questioned the 'sidedness' of the anomaly and postulated that the side of the lip that pulls lowest is the abnormal one. This fails to explain the lack of depression of the angle of the mouth by the DAOM on the other ('normal') side with crying. In the discussion MonreaPI admits that 'we cannot ignore the previous work gathered by others and View publication stats 231 admit that the hypoplasia of the DAOJ\l may exist in some cases'. In search of aetiological facrors chromo ome studies ha\'e been carried out on a rotal of 20 children with \\'eakness of the DAO,\l and congenital anomalies.'-'·9 II No consistent or significant abnormalities were found. To this may be added 2 of our patients who were found to have normal karyotypes. However, we observed an asymmetrical crying facies in a child with trisom\' 18. This appears ro be the first documented instance linking the findings bf weakness of the DAOM and a chromosomal abnormality. Further re\'iew of the literature regarding trisomy 1 revealed comments1~ ~ 1 that facial as\'mmetry or facial palsy has been obsen'ed in less than 10% of such patient . Exact figures do not appear to be a\'ailable (P. E. Polani - personal communication), and furthermore the nature of the facial weakness has not been delineated. There is a report 2; of an infant with Edward's syndrome and congenital facial palsy of the lower motor neuron type (invoh'ement of the frontalis, le\'ator palpebrae superioris and lower facial muscles). The author suggested a congenital agenesis of the seventh nerve nucleus. On the other hand, Smith er al. 26 drew attention to the fairly frequent finding of hypoplasia or aplasia of skeletal muscles. The finding of unilateral weakness of the DAOM in our patient with trisomy 18 may be another example in this context. A recent report documents e\'idence for hereditary factors in the aetiology of this muscle anomal y.16 In a series of 37 neonate . \\'ith hypoplasia of the DAOM, there \\'ere 17 first- or econddegree relati\'es with 10\\'er lip asymmetry. J::urther example of a familial incidence have been published.~u, Our study affords further evidence that weakness of the DAOM may occur as an isolated abnormality or may be associated with other anomalies, in particular cardiO\'ascular and skeletal. We support the contention that the finding of an asymmetrical crying facies should be regarded in the same light as that of a single umbilical artery. If present, a careful search should be carried out for other congenital abnormalities. 11.1' REFERE"CES 1. Hoefnagel, D. and Penr\',]. K. 19601: "ew' Engl. ] ..\led .. 262, 1126. 2..\\arina. H. 11953,: Surg. Gmec Ob>let., 96. 433. 3. Cader, G. G. 11967): fled iatric" -to, 666. 4. Idem (1968):]. Pediat., 73, 953. 5. Idem (1969): Arch. Dis. Childh., 44,69. 6. Cadcr, G. G., Blumenfcld, C. .\\. and Andc"an, R. L. (1971): Che>l, 60, 161. 7. Strong, \\'. B. and Silben, D. R. (1969): Amcr. Heart j., 78, 279. 8. "lad\', G. and Falger, G..\\. (1973): Amcr. j. Di,. Child .• 126,120. 9. Vergcr, P., Guillard,] ..\\., Sandler, B. cl ,iI. (1970): Rc\·. l'ediat., 6, 397. 10. Chantler, C. and .\\cEnen·, G. (1971): Proc ra\". Sac..\\cd., 6-t, 20. 11. Anand,]. K. and Butler, L.]. (1973): Develap. Med. Child Neurol., 15, 69. 12. Pape, K. E. and Pickering, D. (1972):]. Pediat., 81, 21. 13. Kendall, H..\1. (1972): CenL Afr.] ..\\cd., 18, 162. 14. "elsan, K. B. and Eng, G. D. 19721:]. Pediat., 81,16. 15. flerlman, .\\. and Rei'ner, S. H. 1973): .-\rch. Di>. Childh., 48. 627. 16. Papadaros, D. A., Alexiau, D., "icalapaulos, A. D. ,'I ,iI. 19741: i~i'[ .. -t9,927. 17. Knight, L. and Ed\\'ard>,]. E. (1974): Circulation, 50, lo·n. 18..-\Iexiou, D...\Ianolidis, C, Papae\'angellou, G. ,'I ,iI. 19761: Arch. Di,. Childh., 51, 91. 19. Hepner, \X·. R. (1951): Pediatric" 8, 494. 20..\1cHugh, H. E., So\\'den, K. A. and Le\'in, .\\. N. (1969): Arch. Orolarmg., 89, 131. 21. .\lonreal, F. J. (1980): Pediatric>, 65, 1-t6. 22. German. J. L., Rankin, J. K., Harrison, P..-\. ,'I ,iI. (1962): j. PediaL, 60, 103. 23. Lew'i" A. j. (1964): I~i'[ .. 65, 92. 24. Polani, P. E. (1967): GU\"s Hosp. Rep., 116,361. 25..\Iandal, B. '\. (1971): J. [ri,h med ..-\;s., 64, 17. 26. Smith, D. \X'., Patau, K., Therman, E. ,'I </1. (19621: J. PediaL, 60, 113. 27..\\iller, .\\. and Hall,]. G. (19791: .-\mer. j. Di,. Child .. 133.743.