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 defectsof 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 malfor-

mations (TTV-OFM)" as a formal genesis syndrome (etiologically

undefined) to include the following clinical entities: (1) aglossia-adac-

tylia 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 differ-

ent 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, submucouscleft palate

Patients with craniofacial anomalies in as-

sociation with malformations of the extremi-

ties characterized by aplasia have been re-

ported in the literature under the collective

headings "oromandibular limb hypogenesis

syndromes (OMLH)" (Hall, 1971; Grolin et

al., 1976) and "terminal transverse defects

with orofacial malformations (TTV-OFM)"

(Temtamy & McKusick, 1978). The craniofa-

Dr. Figueroa is Research Associate, Center for Crani-ofacial Anomalies, Abraham Lincoln School of Medicine,University of Illinois at the Medical Center, Chicago,

Illinois. Dr Pruzansky is Director of Research, Center forCraniofacial Anomalies, Abraham Lincoln School of

cial malformations may include facial and

oral clefts, micrognathia, microglossia, oligo-

dontia, and paresis of various cranial nerves.

Absence of salivary glands and affected mus-

culature have also been reported (Bersu et al.,

1976). The limb anomalies may range from

complete absence of the limb, or its parts, to

hypoplastic fingers and toes.

This group of patients should be distin-

guished from those exhibiting the amniotic

band syndrome because the pathogenesis of

the malformations associated with the ring

constrictions, amputations and deformations

produced by the bands is clearly differentMedicine, University of Illinois at the Medical Center, -Chicago, Illinois."

Address editorial correspondence to Drs. Figueroa andPruzansky at the Center for Craniofacial Anomalies,Abraham Lincoln School of Medicine, University of II-linois Medical Center, P.O. Box 6998, Chicago, IL 60680.

This investigation was supported in part by grantsfrom the National Institutes of Health (DE 02872) andMaternal and Child Health Services, Department ofHealth and Human Services. '

139

(Torpin, 1968; Temtamy & McKusick, 1978).

Further, the amniotic bands do not account

for other phenotypic characteristics of the

TTV-OFM syndromes, i.e., oligodontia, mi-

crognathia, anomalous tongue, absence of sal-

ivary glands and cranial nerve defects (Cohen

et al., 1971; Garner & Bixler, 1969; Wexler

and Novark, 1974). However, Hall (1971)

140 __Cleft Palate Journal, April 1982, Vol. 19 No. 2

included the amniotic band syndrome in his

table of OMLH syndromes.

The term TTV-OFM syndrome is preferred

because it is clear when it refers to the type of

limb malformations. Implied is a total am-

putation across the distal end of the limb or

a portion of it (ie., digits, fingers or toes). The

facial malformations encountered are wide-

ranging and non-specific. The term OMLH

syndromes, as suggested by Hall (1971), is

limiting because it is based on the assumption

that hypoglossia is present in all cases. Review

of the literature indicated that the tongue

may be affected in different ways, ranging

from macro to microglossia, or it may not be

affected at all (Cosack, 1953; Garner & Bixler,

1969; Wexler & Novark, 1974; Herrmann et

al., 1976).

Considerable overlap exists in the pheno-

typic characteristics displayed by the patients

described under the different diagnostic head-

ings that may be considered TTV-OFM syn-

dromes. Such clinical entities include the

hypoglossia-hypodactyly (aglossia-adactylia)

syndrome, ankyloglossum (superius) syn-

drome, Hanhart syndrome, Mobius syn-

drome, Charlie "M" syndrome, glossopalatine

ankylosismicroglossia-hypodontia-limbanom-

alies syndrome, etc. (Spivack & Bennett, 1968;

Herrmann et al., 1976; Gorlin et al., 1976;

Temtamy & McKusick, 1978).

The purpose of this paper is to present a

patient that may be included with the TTV-

OFM syndromes and whose facial character-

istics are somewhat different from those de-

scribed in the literature including an eccentric

submucous cleft of the hard palate and zona

pellucida of the soft palate.

Case presentation

CCFA #2912 This black female was born

prematurely at six months of gestational age

with multiple congenital facial and limb

anomalies. Birth weight was 1342 gms. She

was the fifth child born to non-consanguinous

parents. The mother was treated for an un-

determined infection during the fifth month

of pregnancy (unknown medication, probably

an antibiotic). The growth and development

of the child have been adequate, requiring no

special care.

On clinical examination at 12 years, 3

months of age, the facial skin had a normal

appearance and texture. The right eye was

microphthalmic, with opaque microcornea

and no vision. The left eye was normal and

well positioned. The midface appeared hy-

poplastic but symmetrical. The lips were nor-

mal in appearance except that the lower lip

was relatively protrusive. The mandible ap-

peared symmetrical and prognathic (Figure

1). Dental development was in the late mixed

dentition stage, with a class III molar relation

and bilateral buccal crossbite. In occlusion,

she appeared overclosed with reduced facial

vertical dimension. The right side of the hard

and soft palate was smaller. An eccentric sub-

mucous cleft of the hard palate with zona

pellucida of the soft palate was observed (Fig-

ure 2). On sustained phonation /a/, the soft

palate elevated and deviated to the left. The

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

tongue was apparently normal in size, posi-

tion, tone, posture, and function.

Examination of the neck, back and chest

was normal. She presented normal pubertal

secondary sex characteristics. The range of

motion and length of the extremities were

normal; however, abnormalities of the distal

portions were evident (Figure 3). On the right

hand the second finger had clinodactyly and

a normal nail. The fingers were absent on the

left hand with small fleshy nubs in the first

and fifth finger positions. The right foot

showed absence of the great toe and hypo-

plastic second toe. The left foot had hypo-

plastic great, second, and third toes. Chro-

mosome analysis yielded a normal female kar-

yotype, 46 XX.

Radiographic findings: Marked digital

impressions on the endocranial surface of the

frontal bone were noted. Although suggestive

of craniostenosis, there was no record of symp-

toms suggestive of increased intracranial pres-

sure. There was absence of many permanent

teeth (13, 12, 11, 21, 22, 23, 44, 46, 47-F.D.I.

nomenclature). The maxilla was retruded in

relation to the cranium. The mandible ap-

peared normal in form and structure, but was

prognathic in relation to the cranium. The

anterior nasal spine was identified radio-

graphically indicating that the premaxilla

was present (Figure 4). Superimposition of

serial tracings demonstrated a facial growth

pattern (Figure 5) in which the original max-

illary-mandibular disharmony was accen-

tuated by virtue of greater incremental

141Figueroa and Pruzansky, trv-orm

growth of the mandible. The lateral cephalo-

metric radiographs revealed adequate velar

movement and velopharyngeal closure during

sustained production of the /s/ sound but not

in the /u/ sound where a 5 mm. gap was

measured.

Radiographs demonstrated normal carpal

and metacarpal bones in both hands, with

complete aphalangia with the exception of

the curved right second finger (Figure 6).

Speech: Her speech has been recorded as

"amazingly good" with an intelligibility of

60-65%, despite the presence of a submucous

cleft palate and the absence of maxillary an-

terior teeth.

Discussion

As previously stated by Gorlin et al. (1976),

syndromes of oromandibular limb hypogene-

sis are confusing because of the variable pat-

tern of craniofacial and limb malformations

encountered. The limbs may be affected in

different ways and degrees (from hypoplastic

toes and fingers to complete limb absence)

and there is no pattern regarding what part,

or how many limbs may be affected. This

diversity in expression appears to occur in the

orofacial region and does not follow a typical

pattern either. As described in excellent re-

views by others (Gorlin et al., 1976; Herr-

mann et al., 1976; Temtamy and McKusick,

1978) it is possible to find orbital hypertelor-

ism, cranial nerve involvement, clefts of the

face and palate, micrognathia, microglossia,

FIGURE 2. CCFA #2912, female, age 10 years, 11 months. Note absence of several maxillary teeth. The arrowon 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 showsabsent 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 revealsendocranial digital impressions, a long and thin anterior nasal spine (arrows), maxillary antero-posterior deficiencyand mandibular prognathism with the teeth in occlusion. The posteroanterior cephalometric headplate is notremarkable.

Cora 291298--- AGE 4-4mH AGE 10-11

FIGURE 5. CCFA #2912, superimposition of lateralcephalometric tracings at the ages of 4 years, 4 monthsand at 10 years, 11 months, reveals similar skeletal char-acteristics at both ages.

FIGURE 6. CCFA #2912, female, age 10 years, 11months. The hand x-rays reveal complete aphalangiawith the exception of the right second finger which isabnormally curved (clinodactyly). The distal ends of thethird and fourth metacarpals in both hands are hypo-plastic.

ankyloglossia, oligodontia, dental anomalies,

etc.

The patient examined in this paper pre-

sented a diagnostic problem because she did

not fit into any of the known clinical entities

grouped under TTV-OFM syndromes. Glos-

sopalatine ankylosis syndrome was ruled out

because the tongue was free and the mandible

was not hypoplastic. The findings did not fit

the conventional definition and description of

the Hanhart syndrome because prognathism

Figueroa and Pruzansky, Trv-orm 143

rather than micrognathia was present. Our

patient would fit under the broader umbrella

defined by Herrmann et al. (1976) for the

Hanhart syndrome. The hypoglossia-hypo-

dactyly syndrome was excluded on the basis

of the presence of a normal tongue and a

prognathic mandible. The Charlie "M" syn-

drome was excluded because of the absence

of hypertelorism, antimongoloid slant of the

eyes and facial paralysis. Also, Mobius syn-

drome 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-

sence of maxillary incisors, as in our case. The

relative prognathism of the mandible in rela-

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 man-

dible was greater than the normal value, rein-

forcing our impression of mandibular prog-

nathism. 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

female with unilateral hypoglossia, ankylog-

lossia, oligodontia hypodactylia and promi-

nent mandible.

Eye anomalies observed in this patient have

also been reported in Mobius syndrome (Ev-

ans, 1955).

The atypical anatomical and functional

characteristics in the palate area are of in-

terest. The deviation of the soft palate to the

left during phonation may be due to a mus-

cular derangement in the soft palate as a

result of the submucous cleft palate, or to

possible partial deficiency of cranial nerves

VII, IX and X (Nishio et al., 1976, a,b)

innervating the right side of the soft palate.

The latter possibility brings our patient closer

to Herrmann's (1976) definition of Hanhart

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

syndrome which includes cranial nerve in-

volvement.

Most of the cases affected with TTV-OFM

syndromes are sporadic and because of the

extreme variability in the type of limb and

facial anomalies observed, it is thought that

these conditions are probably etiologically

heterogeneous (Cohen et al., 1971; Gorlin et

al., 1976; Herrmann et al., 1976; Temtamy

& McKusick, 1978).

Summary

This report presents a patient affected with

limb and orofacial congenital malformations.

The patient may be included under the gen-

eral diagnostic heading of TTV-OFM syn-

dromes (Temtamy & McKusick, 1978) or un-

der Herrmann's (1976) definition of Hanhart

syndrome. The limb anomalies are similar to

those reported in the literature. The facial

characteristics are somewhat different in that

our patient presents true mandibular prog-

nathism instead of the commonly reported

mandibular hypoplasia or retrognathism.

Submucous cleft of the hard palate and zona

pellucida of the soft palate were associated

findings.

Acknowledgment: The authors wish to thank

David Leu, Robert Balmes and Mae Esler for

photographic and artistic assistance, and Bar-

bara Grilli for the preparation of this manu-

script.

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