Terminal Transverse Defects with Orofacial Malformations (TTV-OFM)

Terminal Transverse Defects with Orofacial Malformations

(TTV-OFM): Case Report with Mandibular Prognathism and

Submucous Cleft Palate

ALVARO FIGUEROA, D.D.S SAMUEL PRUZANSKY, D.D.S. Chicago, Illinows 60680

Terminal transverse defects of varying severity, ranging from aplasia of phalanges and digits to hemimelia, have been reported in association with various orofacial malformations. Temtamy and McKusick (1978) introduced the term "terminal transverse defects with orofacial malformations (TTV-OFM)" as a formal genesis syndrome (etiologically undefined) to include the following clinical entities: (1) aglossia-adactylia syndrome; (2) ankyloglossum (superius) syndrome; (3) Hanhart syndrome; (4) ectrodactyly with OFM; and (5) Mobius syndrome with digital malformations (including the Charlie "M" syndrome). This report describes a patient whose phenotypic characteristics qualify for inclusion under this heading, but with facial features somewhat different from those previously reported in the literature including the presence of an eccentric submucous cleft of the hard palate and zona pellucida of the soft palate.

KEY WORDS: Terminal transverse defects, orofacial malformations, submucous cleft palate

Patients with craniofacial anomalies in as- cial malformations may include facial and sociation with malformations of the extremi- oral clefts, micrognathia, microglossia, oligo- ties characterized by aplasia have been re- dontia, and paresis of various cranial nerves. ported in the literature under the collective Absence of salivary glands and affected mus- headings "oromandibular limb hypogenesis culature have also been reported (Bersu et al., syndromes (OMLH)" (Hall, 1971; Grolin et 1976). The limb anomalies may range from al., 1976) and "terminal transverse defects complete absence of the limb, or its parts, to with orofacial malformations (TTV-OFM)" hypoplastic fingers and toes. (Temtamy & McKusick, 1978). The craniofa- This group of patients should be distin- guished from those exhibiting the amniotic Dr. Figueroa is Research Associate, Center for Crani- band syndrome because the pathogenesis of ofacial Anomalies, Abraham Lincoln School of Medicine, University of Illinois at the Medical Center, Chicago, the malformations associated with the ring Illinois. Dr Pruzansky is Director of Research, Center for constrictions, amputations and deformations Craniofacial Anomalies, Abraham Lincoln School of produced by the bands is clearly different Medicine, University of Illinois at the Medical Center, - (Torpin, 1968; Temtamy & McKusick, 1978). Chicago, Illinois." Address editorial correspondence to Drs. Figueroa and Further, the amniotic bands do not account Pruzansky at the Center for Craniofacial Anomalies, for other phenotypic characteristics of the Abraham Lincoln School of Medicine, University of II- TTV-OFM syndromes, i.e., oligodontia, mi- linois Medical Center, P.O. Box 6998, Chicago, IL 60680. crognathia, anomalous tongue, absence of sal- This investigation was supported in part by grants ivary glands and cranial nerve defects (Cohen from the National Institutes of Health (DE 02872) and Maternal and Child Health Services, Department of et al., 1971; Garner & Bixler, 1969; Wexler Health and Human Services. ' and Novark, 1974). However, Hall (1971) 139 140 Cleft Palate Journal, April 1982, Vol. 19 No. 2 __ included the amniotic band syndrome in his submucous cleft of the hard palate and zona table of OMLH syndromes. pellucida of the soft palate. The term TTV-OFM syndrome is preferred because it is clear when it refers to the type of Case presentation limb malformations. Implied is a total am- putation across the distal end of the limb or CCFA #2912 This black female was born a portion of it (ie., digits, fingers or toes). The prematurely at six months of gestational age facial malformations encountered are wide- with multiple congenital facial and limb ranging and non-specific. The term OMLH anomalies. Birth weight was 1342 gms. She syndromes, as suggested by Hall (1971), is was the fifth child born to non-consanguinous limiting because it is based on the assumption parents. The mother was treated for an un- that hypoglossia is present in all cases. Review determined infection during the fifth month of the literature indicated that the tongue of pregnancy (unknown medication, probably may be affected in different ways, ranging an antibiotic). The growth and development from macro to microglossia, or it may not be of the child have been adequate, requiring no affected at all (Cosack, 1953; Garner & Bixler, special care. 1969; Wexler & Novark, 1974; Herrmann et On clinical examination at 12 years, 3 al., 1976). months of age, the facial skin had a normal Considerable overlap exists in the pheno- appearance and texture. The right eye was typic characteristics displayed by the patients microphthalmic, with opaque microcornea described under the different diagnostic head- and no vision. The left eye was normal and ings that may be considered TTV-OFM syn- well positioned. The midface appeared hy- dromes. Such clinical entities include the poplastic but symmetrical. The lips were nor- hypoglossia-hypodactyly (aglossia-adactylia) mal in appearance except that the lower lip syndrome, ankyloglossum (superius) syn- was relatively protrusive. The mandible ap- drome, Hanhart syndrome, Mobius syn- peared symmetrical and prognathic (Figure drome, Charlie "M" syndrome, glossopalatine 1). Dental development was in the late mixed ankylosismicroglossia-hypodontia-limbanom- dentition stage, with a class III molar relation alies syndrome, etc. (Spivack & Bennett, 1968; and bilateral buccal crossbite. In occlusion, Herrmann et al., 1976; Gorlin et al., 1976; she appeared overclosed with reduced facial Temtamy & McKusick, 1978). vertical dimension. The right side of the hard The purpose of this paper is to present a and soft palate was smaller. An eccentric sub- patient that may be included with the TTV- mucous cleft of the hard palate with zona OFM syndromes and whose facial character- pellucida of the soft palate was observed (Fig- istics are somewhat different from those de- ure 2). On sustained phonation /a/, the soft scribed in the literature including an eccentric palate elevated and deviated to the left. The

FIGURE 1. CCFA #2912, female, age 12 years, 7 months. Note the relative midface hypoplasia and redundant lower lip.

Figueroa and Pruzansky, trv-orm 141 tongue was apparently normal in size, posi- growth of the mandible. The lateral cephalo- tion, tone, posture, and function. metric radiographs revealed adequate velar Examination of the neck, back and chest movement and velopharyngeal closure during was normal. She presented normal pubertal sustained production of the /s/ sound but not secondary sex characteristics. The range of in the /u/ sound where a 5 mm. gap was motion and length of the extremities were measured. normal; however, abnormalities of the distal Radiographs demonstrated normal carpal portions were evident (Figure 3). On the right and metacarpal bones in both hands, with hand the second finger had clinodactyly and complete aphalangia with the exception of a normal nail. The fingers were absent on the the curved right second finger (Figure 6). left hand with small fleshy nubs in the first Speech: Her speech has been recorded as and fifth finger positions. The right foot "amazingly good" with an intelligibility of showed absence of the great toe and hypo- 60-65%, despite the presence of a submucous plastic second toe. The left foot had hypo- cleft palate and the absence of maxillary an- plastic great, second, and third toes. Chro- terior teeth. mosome analysis yielded a normal female kar- yotype, 46 XX. Discussion Radiographic findings: Marked digital impressions on the endocranial surface of the As previously stated by Gorlin et al. (1976), frontal bone were noted. Although suggestive syndromes of oromandibular limb hypogene- of craniostenosis, there was no record of symp- sis are confusing because of the variable pat- toms suggestive of increased intracranial pres- tern of craniofacial and limb malformations sure. There was absence of many permanent encountered. The limbs may be affected in teeth (13, 12, 11, 21, 22, 23, 44, 46, 47-F.D.I. different ways and degrees (from hypoplastic nomenclature). The maxilla was retruded in toes and fingers to complete limb absence) relation to the cranium. The mandible ap- and there is no pattern regarding what part, peared normal in form and structure, but was or how many limbs may be affected. This prognathic in relation to the cranium. The diversity in expression appears to occur in the anterior nasal spine was identified radio- orofacial region and does not follow a typical graphically indicating that the premaxilla pattern either. As described in excellent re- was present (Figure 4). Superimposition of views by others (Gorlin et al., 1976; Herr- serial tracings demonstrated a facial growth mann et al., 1976; Temtamy and McKusick, pattern (Figure 5) in which the original max- 1978) it is possible to find orbital hypertelor- illary-mandibular disharmony was accen- ism, cranial nerve involvement, clefts of the tuated by virtue of greater incremental face and palate, micrognathia, microglossia,

FIGURE 2. CCFA #2912, female, age 10 years, 11 months. Note absence of several maxillary teeth. The arrow on the maxillary cast shows the eccentric position of the right submucous cleft palate.

142 Cleft Palate Journal, April 1982, Vol. 19 No. 2

FIGURE 3. CCFA #2912, female, age 12 years, 3 months. The only digit present was a clinodactylic second finger on the right hand. Note small nubs in the first and fifth finger position on the left hand. The right foot shows absent great toe and hypoplastic second toe. The left foot presents hypoplastic great, second and third toes.

O©CCLUSION REST FIGURE 4. CCFA #2912, female, age 10 years, 11 months. The lateral cephalometric radiographs reveals endocranial digital impressions, a long and thin anterior nasal spine (arrows), maxillary antero-posterior deficiency and mandibular prognathism with the teeth in occlusion. The posteroanterior cephalometric headplate is not remarkable.

Figueroa and Pruzansky, Trv-orm 143

rather than micrognathia was present. Our patient would fit under the broader umbrella Cora 291298 defined by Herrmann et al. (1976) for the --- AGE 4-4 Hanhart syndrome. The hypoglossia-hypo- mH AGE 10-11 dactyly syndrome was excluded on the basis of the presence of a normal tongue and a prognathic mandible. The Charlie "M" syndrome was excluded because of the absence of hypertelorism, antimongoloid slant of the eyes and facial paralysis. Also, Mobius syndrome was excluded because there was no involvement of cranial nerve VI. The mimetic musculature and eye motility in the right eye were normal and there was a normal chest wall structure. Cosack (1953) and Shear (1956) reported cases with premaxillary hypoplasia and ab- FIGURE 5. CCFA #2912, superimposition of lateral cephalometric tracings at the ages of 4 years, 4 months sence of maxillary incisors, as in our case. The and at 10 years, 11 months, reveals similar skeletal char- relative prognathism of the mandible in rela- acteristics at both ages. tion to the anterior cranial base could be due to a short anterior cranial base, an intrinsi- cally longer mandible, or a combination of both. Unfortunately, normative values for blacks matched for age and sex were not available. When compared with matched data on white females (Riolo et al., 1974), the length of the anterior cranial base was within normal limits, whereas the length of the mandible was greater than the normal value, rein- forcing our impression of mandibular prognathism. Since mandibular micrognathia was the usual mandibular characteristic reported (Garner & Bixler, 1969; Wexler & Novark, 1974; Gorlin et al., 1976; Herrmann et al., 1976; Temtamy & McKusick, 1978), the find- ing of mandibular prognathism makes the present case exceptional. However, Lustmann et al (1981) recently reported a 17 year black FIGURE 6. CCFA #2912, female, age 10 years, 11 female with unilateral hypoglossia, ankylog- months. The hand x-rays reveal complete aphalangia lossia, oligodontia hypodactylia and promi- with the exception of the right second finger which is abnormally curved (clinodactyly). The distal ends of the nent mandible. third and fourth metacarpals in both hands are hypo- Eye anomalies observed in this patient have plastic. also been reported in Mobius syndrome (Ev- ans, 1955). ankyloglossia, oligodontia, dental anomalies, The atypical anatomical and functional etc. characteristics in the palate area are of in- The patient examined in this paper pre- terest. The deviation of the soft palate to the sented a diagnostic problem because she did left during phonation may be due to a mus- not fit into any of the known clinical entities cular derangement in the soft palate as a grouped under TTV-OFM syndromes. Glos- result of the submucous cleft palate, or to sopalatine ankylosis syndrome was ruled out possible partial deficiency of cranial nerves because the tongue was free and the mandible VII, IX and X (Nishio et al., 1976, a,b) was not hypoplastic. The findings did not fit innervating the right side of the soft palate. the conventional definition and description of The latter possibility brings our patient closer the Hanhart syndrome because prognathism to Herrmann's (1976) definition of Hanhart

144 Cleft Palate Journal, April 1982, Vol. 19 No. 2 syndrome which includes cranial nerve in- 1971. volvement. Cosack, G., Die angeborene Zungen-Munddach-Ver- wachsung als Leitmotive eines Komplexes von multi- Most of the cases affected with TTV-OFM plen Abartugen, Ztschr. Kinderh., 72: 240, 1953. syndromes are sporadic and because of the Evans, P. R., Nuclear agenesis (Mobius syndrome the extreme variability in the type of limb and congenital facial diplegia syndrome), Arch. Dis. Child., facial anomalies observed, it is thought that 30: 237, 1955. Garner, L. D. and Bixier, D. D., Micrognathia, an these conditions are probably etiologically associated defect of Hanhart's syndrome. Types II and heterogeneous (Cohen et al., 1971; Gorlin et III, Oral Surg., Oral Med., and Oral Path., 27: 601, 1969. al., 1976; Herrmann et al., 1976; Temtamy Gorin, R. J., PinpBorc, J. J. and Conmen, M. M., Jr., & McKusick, 1978). Syndromes of the Head and Neck, New York: Mc- Graw-Hill, 1976. Summary Hart, B. D., Aglossia-adactylia, Birth Defects: Orig. Art. Series, Vol. 7, No. 7: 233, 1971. This report presents a patient affected with Herrmann, J., ParusteER, P. D., Gi1BERT, E. F., ViseskuL, limb and orofacial congenital malformations. C., Bersuv, E., PEtrERsEN, J. C., and OPITZ, J. M., The patient may be included under the gen- Studies of malformation syndromes of man XXX XIB: Nosologic studies in the Hanhart and Mobius syn- eral diagnostic heading of TTV-OFM syndrome, Europ. J. Pediat., 122: 19, 1976. dromes (Temtamy & McKusick, 1978) or un- LustmanN, J., Luris, R., Strutuers, P. and Garwoon, der Herrmann's (1976) definition of Hanhart A., The hypoglossia-hypodactylia syndrome: Report of syndrome. The limb anomalies are similar to two cases, Oral Surg., 51: 403, 1981. NisH10, J., MaTsuvya, T., MacHipa, J., and Mryazax1, T., those reported in the literature. The facial The motor nerve supply of the velopharyngeal muscles, characteristics are somewhat different in that Cleft Palate J., 13: 20, 1976 (a). our patient presents true mandibular prog- NisH10, J., Matsuvya, T., IsuK1I, K., and Mivyazax1, T., nathism instead of the commonly reported Roles of the facial glossopharyngeal and vagus nerves mandibular hypoplasia or retrognathism. in velopharyngeal movement, Cleft Palate J., 13: 201, 1976 (b). Submucous cleft of the hard palate and zona R1or1o, J. L., Moyers, R. E., McNamara, J. A., Jr., and pellucida of the soft palate were associated Hunter, W. S., An Atlas of Craniofacial Growth, findings. Monograph No. 2, Craniofacial Growth Series, Center Acknowledgment: The authors wish to thank for Human Growth and Development, The University David Leu, Robert Balmes and Mae Esler for of Michigan, Ann Arbor, Michigan, 1974. SHuraAr, M., Congenital underdevelopment of the maxilla photographic and artistic assistance, and Bar- associated with partial adactylia, partial anodontia bara Grilli for the preparation of this manu- and microglossia, J. Dent. Assn. South Africa, 11: 78, script. 1956. . Spivack, J. and BENNETT, J. E., Glossopalatine ankylosis, References: Plast. Reconst. Surg., 42: 129, 1968. Brersu, E. T., PettErsEN, J. C., CmarBonEav, W. J. and Trmtamy, S,. A. and McKusick, V. A., The genetics of Opitz, J. M., Studies of malformation syndromes of hand malformations, Birth Defects: Orgi. Art. Series, Vol. man XXXXIA: Anatomical studies in the Hanhart 14, No. 3: 1978. syndrome-A pathogenetic hypothesis, Europ. J. Pe- Torpin, R. C., Fetal Malformations Caused by Amnion diat., 122: 1, 1960. Rupture During Gestation, Springfield, Illinois, Conen, M. M., Jr., Pantk®, H., and Sirs, E., Nosologic Charles C. Thomas, 1968. and genetic considerations in the aglossy-adactyly syn- WrxieEr, M. R. and Novarx, B. W., Hanhart's syndrome Birth Defects: Orig. Art. Series, Vol. 7, No. 7: 237, drome: Case report, Plast. Reconst. Surg., 54: 99, 1974.