Craniofacial and Dental Study

of Mulibrey Nanism

SINIKKA MYLLARNIEMI, D. ODONT.,

KALEVI KOSKI, D. ODONT.,

JAAKKO PERHEENTUPA, M.D.Helsinki, Finland

Denial and craniofacial features of 17 children and young adults suffering from therecently discovered mulibrey nanism syndrome are described and discussed. The present datado not allow any definite craniofacial typification of the syndrome. However, severalfindings suggest that we may be dealing with persistence of infantile structural relation-ships in the craniofacial area.

Introduction

Mulibrey nanism is a recently described

syndrome of growth failure with prenatal on-

set (Perheentupa et al., 1970; Perheentupa et

al., 1973).. The name was coined from muscle,

liver, brain, and eye, the organs most conspic-

uously involved in the first cases observed. So

far, 27 cases from Finland, one of Egyptian

origin from Sweden (Thorén, 1973), two from

Canada, and two from the United States

(Cumming et al., 1976; Voorhess et al., 1976),

and one in a Gipsy from France (L. Catholi-

neau, personal communication) are known to

us. The condition is probably determined by

an autosomal recessive gene (Perheentupa et

al., 1973). It is characterized by a triangular

face, often hydrocephaloid skull, thin hypo-

tonic musculature, peculiar highpitched

voice, ocular fundi with yellowish dots and

pigment dispersion, and raised venous pres-

sure with enlarged liver. The latter features

are due to pericardial constriction, which

seems to be a constant component of the

condition, though highly variable in extent.

Some of those affected die in infancy, but

others reach adulthood without severe inca-

pacity. As the tissues involved seem to be

mainly of mesodermal origin, the basic defect

may be of a gene determining an enzyme or

structural protein which is particularly essen-

tial to mesodermal tissues.

Dr. Myllarniemi is Assistant Professor of Pedodonticsand Orthodontics, Institute of Dentistry, University ofHelsinki. Dr. Koski is Professor of Pedodontics and Or-thodontics, Institute of Dentistry, University of Turku,and Dr. Perheentupa is Associate Professor of Pediatrics,The Children's Hospital, University of Helsinki.

369

The range of adult height is estimated to

be from 136 to 161 cm for males and from

126 to 151 cm for females. Growth failure

seems to be of a rather unusual type for,

although the epiphyses appear normal, the

growth of the limbs is more affected than that

of the trunk. Craniofacial growth also seems

to be characteristically altered. The very typ-

ical craniofacial features have not yet been

described in detail, although some informa-

tion based on the manuscript of the present

report has appeared in a new textbook (Gorlin

et al., 1976). A biometric description of cran-

iofacial characteristics in mulibrey nanism is

the subject of this report.

Subject and methods

Seventeen persons with mulibrey nanism,

eight boys and nine girls aged 1.4 to 24.4

years, were examined. In addition to the clin-

ical dento-facial examination, we took dental

casts, X-ray orthopantomograms, and lateral

cephalograms for all save the youngest pa-

tient.

From the casts, the mesio-distal and labio-

lingual crown dimensions were measured with

a sliding calliper. Morphological characteris-

tics of the dentition and dental occlusion were

also recorded. Dental age, i.e., the stage of

tooth formation, was estimated from the or-

thopantomograms.

Lateral cephalograms were taken using a

cephalostat. The midsagittal plane distance

was a constant 150 cm, and the midsagittal

plane-film distance was 11 cm. Some difficul-

ties encountered when X-raying the youngest

370 _ Cleft Palate Journal, October 1978, Vol. 15 No. 4

children led us to reject five films, so that 11

films, representing five females and six males

aged 6.8 to 24.4 years, qualified for dimen-

sional analysis.

The following linear measurements (Figure

1) were taken from the X-ray cephalograms

with a sliding calliper, read to the nearest

mm.:

gl-op, glabella-opisthocranion, length of the cran-

ium,n-s, nasio-sella, length of anterior cranial base,

b-s, basion-sella, length of posterior cranial

base,o-b, opisthion-basion, length of foramen mag-

num,

o-n, opisthion-nasion,o-a, opisthion-acanthion,o-id, opisthion-infradentale.

._ n-sThe ratio -- was also calculated.

e

The following angular measurements were

made:

F/C, the angle formed by the foramen magnumand the clivus planes,

C/S, the angle formed by the clivus plane andthe planum sphenoideum,

nsb, the angle formed by the n-s and b-s lines,N/M, the angle formed by the nasal floor line and

the mandibular base plane,M/R, the angle formed by the mandibular base

plane and the tangent to the dorsal border

of the ascending ramus,N/U, the angle formed by the nasal floor line and

the axis of the upper incisor,

F/N, the angle formed by the plane of the fora-men magnum and the nasal floor line.

The angles were measured from the lines

representing the respective planes drawn on

transparent paper fixed on the film and read

to the nearest degree.

The choice of the measured dimensions was

determined by available control data on Fin-

nish children and young adults (vide infra).

Results

Information on the youngest children in-

dicated that eruption of the deciduous teeth

had taken place normally.

Dental age, estimated from tooth formation

in ten patients aged 4.5 to 12.8 years was, like

skeletal age (Perheentupa et al., 1973), well

within normal limits when compared to Fin-

nish norms (Haavikko, 1970). The 12.8-year-

old boy was an exception, with dental age

retarded by as much as 2.9 years. His skeletal

maturation was also retarded by 2.3 years.

Labio-lingual and mesio-distal tooth di-

mensions correspond closely to the Finnish

norms (Rantanen, 1964; Alvesalo, 1971).

Traits of dental occlusion are listed in Table

1. Dental arch crowding was a common fea-

ture of the permanent dentition. In several

cases, it had been treated with tooth extrac-

tions. Another frequent abnormality was hy-

podontia of the second praemolars. Many of

the patients had proclination of the upper

incisors. ,

FIGURE 1. The measurement points and planes em-ployed.

TABLE 1. Traits of dental occlusion in 16 patientswith mulibrey nanism

Characteristic Proportion

Class I occlusion 16/16Normal overbite 16/16Crowding of upper dental arch, 9/16>»4mm

Crowding of lower dental arch, 6/16>»4mm

Proclined permanent upper incisors 6/15(>18D)

Hypodontia of one or several second 5/16bicuspids

Overjet >3mm 4/14Lateral cross bite 2/16Lateral scissor bite 1/16

Visual inspection of the mulibrey patientsrevealed a characteristic facies: triangular fa-cial shape, ocular hypertelorism, and a broadand deep nasal bridge (Figures 2 and 3).

In lateral cephalograms (Figure 4), theskulls appeared long in relationship to thedelicate facial structures. Frontal "bossing"was evident. The nuchal plane of the occipitalbone seemed to lie horizontally, but the an-gulation of the lambdoid suture to the cranialbase structures appeared normal.

Myllarniemi et al., Murisrey Nanism SynpromE 371

In most of the patients the frontal andsphenoidal sinuses were either totally absentor were clearly smaller than what was consid-ered normal for age (Table 2). In six of the 16cephalograms the nasal bones were found tobe in a vertical position and close to themedial orbital wall. Both the position and theappearance of the sella turcica were abnor-mal. The posterior cranial base seemed to beshort and the cranial base angle large.

The tongue appeared small in relationship

FIGURE 2. Facial appearance of patients with mulibrey nanism aged 24, 17, 14, 8, 7 and 5.

372 Cleft Palate Journal, October 1978, Vol. 15 No. 4

FIGURE 3. Profile appearance of the same patients.

Myllarniemi et al., Murisrey Nanism Synproms 373

FIGURE 4. Lateral cephalograms of the same mulibrey patients as in Figures 2 and 3. Note characteristic formofsella, short clivus, long foramen magnum, frontal bossing, small frontal and sphenoidal sinuses, obtuse gonial angleand horizontal nuchal plane. Vertical nasal bones in the patients at top right and middle left.

374 Cleft Palate Journal, October 1978, Vol. 15 No. 4

TABLE 2. Characteristics of skull structure in nor-

mal lateralis of 16 patients with mulibrey nanism

Characteristic Proportion

Long, shallow sella turcica 15/16Missing or small frontal sinus 13/16Missing or small sphenoidal sinus 14/16Horizontal nuchal plane 12/16

Frontal "bossing" 11/16Relatively small tongue 10/16Vertical nasal bone 6/16

Small maxillary sinus 4/16

to the oral cavity in most instances. The hyoid

bone could not be detected in all of the films,

but in several patients, it was abnormally

high, close to the mandibular border.

Results of linear and angular measure-

ments are presented graphically in Figure 5.

The linear dimensions were generally smaller

than the age- and sex-specific means for Fin-

nish children and young adults (Koski 1960,

Aantaa and Koski 1962, Koski 1965, Koski-

nen and Koski 1965). The only exceptions

were the lengths of the skull and foramen

magnum. The clivus, b-s, was relatively the

shortest dimension measured. The ratio be-

tween the two cranial base components, n-

s/b-s, was clearly abnormal. Its range in these

patients was 1.5 to 2.5, whereas, in a normal

population, the value is close to 1.5 at all age

levels (Koski, 1960).

In contrast to the linear dimensions, the

angular measures tended to be larger than the

reference means. The ranges for the angles

foramen plane/clivus, nasal floor/mandibu-

lar base plane, and mandibular base/ramus

tended to be large. On the other hand, the

distribution of the angles clivus/sphenoidal

plane and foramen plane/nasal floor were

fairly close to normal.

Discussion

The recentlydiscovered new form of pre-

natal growth failure which has been named

mulibrey nanism (Perheentupa et al., 1970)

appears to entail several peculiar cranio-facial

features. So far the number of known affected

individuals is rather small, and the cranio-

facial features observed in these individuals

are so diversified that clear-cut typification in

this respect is not yet possible. Nevertheless,

some of the findings seem to merit discussion.

From the purely dental point of view, the-

only abnormally frequent findings were

crowding of teeth and hypodontia of the sec-

ond bicuspid. The former finding may be

associated with the smallness of the jaws,

whereas the latter feature remains unex-

plained.

The absence or smallness of frontal sinuses

when correlated with the frontal "bossing"

can perhaps be explained in terms of "func-

tional craniology" (Moss and Young, 1960).

Protection of the eye-balls from above does

not, in these individuals, depend on the out-

ward growth and concomitant pneumatiza-

tion of the frontal bone immediately above

the orbits. On the other hand, the deficiency

of the sinuses, including the sphenoidal sinus,

may be an infantile trend (vide infra). 'A depressed nasal bridge is a feature of

several craniofacial malformations involvingcartilage disorders. Whether its occurrence insome of these patients can be similarly ex-plained cannot be determined at the presenttime.The relatively high position of the hyoid

bone in many of these patients, in conjunctionwith the horizontally positioned nuchal plane,prompts the question as to whether it indi-cates relative shortness of the neck region and,if so, whether this contributes to the typicalhigh-pitched voice of the mulibrey-patients(Perheentupa et al., 1970). Further studies are

needed to answer these questions.Among the generally smaller than normal

cranial dimensions, the lengths of the skulland the foramen magnum are interesting ex-ceptions. The normality of the latter dimen-sion can be taken as an indication of normalgrowth at the circumforaminal synchon-droses. Thus a generalized growth disturbancein the chondrocranial cartilage tissues, as seenin achondroplasia, appears to be ruled out.The normal length of the brain capsule incontrast to the subnormal lengths of the com-ponents of the skull base and the face seemsto indicate that adequate space for the brainhas been obtained by compensatory growthof the calvarium, which bulges in both thefrontal and occipital regions.The peculiar shape of the sella turcica is

typical of this syndrome (Perheentupa et al.,1970). It resembles the shape of the bonysphenoid before the cartilaginous dorsum sel-lae has ossified, a process which normally .

F/C

- 5 -~4 - 3-2-1 - 1 +41 +2 +3 +4 +5

- 71- 6 - 5 - 4 - 3 - 2 - 4 +1 +2 e e-1 +1 + 2 +3 + 4 + 5

ns/sb

+ 1 +2 - 1 + 1 + 2 + 3 + 4 + 5

& oie-7- 6 - § -4 - 3 - 2-1 - 100 +1 +2+3 +4 +5

-7- 6-5-4 - 3 - 2-4 - 10 +1 +2+3 +4 +5

o-id

-7-6-5-4 +2 -1 [+1 +4 +5

gl - op

|___]- 2-1 +1+2+3+4 +5

-T-6-5-4 - 3 - 2 -d

FIGURE 5. Deviation of the linear and angular cephalometric measurements from the normal mean in SD units.The lowest columns represent one patient.

375

376 Cleft Palate Journal, October 1978, Vol. 15 No. 4

takes place gradually after five years of age

(Latham, 1972). If ossification is delayed in

these patients, the shortness of the clivus is

also explained by another infantile feature,

the low position of the sellar fossa.

Some of the angular relationships also in-

dicate a lag in development. At birth, the

angle between the foraminal plane and the

clivus is large, and the clivus normally

straightens up during postnatal growth

(Kummer, 1952; Koski, 1960). The skull base

angle, nasio-sella-basion, is large during late

fetal life (Kvinnsland 1969), and its abnor-

mally skewed distribution towards the large

side in the present series could be viewed as

due to persistence of an early structural fea-

ture.

The facial appearance of the mulibrey pa-

tients resembles patients affected with another

prenatal growth disorder, the Silver-Russell

syndrome (Silver et al., 1953; Russell, 1954;

Tanner et al., 1975). In this condition, the

face is also triangular, and the neuro-cranium

appears large. Teeth erupt normally and form

severely crowded dental arches (Silver and

Gruskay, 1957; Silver, 1959; Rossier, 1962;

Silver, 1964). No cephalometric descriptions

are available of the craniofacial features of

Silver-Russell patients. Inspection of pub-

lished pictures (Lassker and Reich, 1969) and

our own observations on three patients show

normal sella and normal cranial base struc-

tures while the discrepancy between the facial

and cranial parts is even more pronounced.

In progeria, a growth disorder in which the

affected child resembles an aged person, the

characteristic facies results from retardation

of facial growth in the presence of normal

growth of the neurocranium (Rosenthal et al.,

1956).

Looked upon as a whole, in mulibrey pa-

tients, the shape of the skull and the size

relationship between the skull and the face

resemble those seen normally in newborn and

young infants A tempting interpretation,

therefore, is that the characteristic facies is the

result of lagging development of the craniofa-

cial skeleton. This interpretation would at

least be in accord with the generalized growth

disturbance seen in this syndrome (Perheen-

tupa et al., 1973). We hope that longitudinal

studies of young patients will clarify the na-

- ture of the craniofacial abnormalities.

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