Cephalometric measurements of familial dwarfism and high plasma immunoreactive growth hormone Raphael Konfino, D.M.D.,* Zvi Laron, M.D.***
Petah-T&a,
Athalia
Pertzelan,
M.D.,**
and
Israel
I
n 1966, Laron, Pertzelan, and Mannheimer’ described a syndrome of familial dwarfism which was indistinguishable both clinically and in many of the laboratory findings from pituitary dwarfism but in which there were abnormally high plasma concentrations of immunoreactive human growth hormone (IR-HGH). The possibility was raised that in these cases the circulating growth hormone is biologically inactive but immunologically active. Additional clinical and laboratory findings in these and newly discovered patients, all of whom were of Jewish origin, were later reported. 2l 3 An increasing awareness of this syndrome led to the finding of several non-Jewish patients in other countries.3 One of the typical features of this syndrome is a small face and mandible, which gives the false impression of a large head (Fig. 1). Scharf anti Laron4 calculated the ratio between the bicondylar and biparietal diameters from anteroposterior roentgenograms of the skull and found t,hat they were significantly below normal values. The purpose of this investigation was to study the dimension and orientation From
the
Institute
of
Pediatric
and
Adolescent
Endocrinology,
Supported in part by a grant from the Faculty for Tel Aviv University. “Lecturer in Orthodontics, Faculty of Continuing School of Medicine, Tel Aviv University. **Senior Lecturer in Pediatrics, and Senior Assistant, Institute Hospital. ***Profewor University; Hospital; Health.
196
of
Sacklcr Pediatric
School and
Continuing Medical
Beilinson Medical Education,
of Medicine, Tel Aviv Adolescent Endocrinology,
of Pediatric Endocrinology, Sackler School of Medicine, Director, Institute of Pediatric and Adolescent Endocrinology, Established Investigator of the Chief Scientist’s Bureau,
Hospital. Education, Sackler University, Beilinson Tel Aviv Beilinson Ministry of
Familial
Fig.
1. The
age
7942
head
of
a male
patient
with
dwarfism
familial
and high plasma IR-HGH
dwarfism
and
high
plasma
IR-HGH
197
at
years.
of a number of the skeletal elements of the profile of these patients using lateral cephalometric head films. Materials
and
methods
For this study, ten lateral cephalograms of patients with the syndrome of familial dwarfism and high plasma IR-HGH were made under standardized conditions with the same cephalostat. They presented sufficient criteria for accurate measurements. The chronologic ages of the patients ranged from 9 to 18 years (three patients were 9 years old, two 11 years, one 13 years, one 14 years, two 16 years, and one 18 years old). For comparative purposes, a group of normal children and adolescents, matched for age and sex, were studied by the same methods. The following linear and angular measurements were taken in the patients and controls (Fig. 2). Linear measurements (in millimeters) 1. Anteroposterior head length : measured between the most prominent points in the forehead and back of the skull. distance between basion and nasion (Ba-N). 2. Total length of the cranial base: 3. Length of the anterior cranial base : sella-nasion (S-N). 4. Length of the posterior cranial base: sella-articulare ( S-Ar) . 5. Total length of the mandible: articulare-pogonion (Ar-Pog). 6. Length of the ramus of the mandible : articulare-gonion (Ar-G) . 7. Length of the corpus of the mandible : gonion-pogonion (Go-Pog). 8. Length of the maxilla: anterior nasal spine-posterior nasal spine (ANS-PNS). 9. Length of the maxillary apical base: subspinale-posterior nasal spine (A-PNS). Angular measurements (Fig. 3) S-N-A (sella-nasion-subspinale) : this angle measures the degree of maxillary prognathism.
Fig.
2. Linear
measurements.
S-N-B (sella-nasion-supramentale) : this angle shows the anterior limit of the mandibular basal arch in relation to the anterior cranial base. N-S-Ar (nasion-sella-articulare) : this cranial base angle indicates the degree of bending of the cranial base. angle determines the angulation between Ar-G-Gn (articulare-gonion-gnathion) : this the ramus and corpus of the mandible. angle is formed between the Frankfort FMA (Frankfort-mandibular angle) : this horizontal reference plane and the mandibular plane.
Head length. Statistically no significant difference was found in this measurement between the patients and the normal group (t = 0.84, p. > 0.1). Cranial base. The total cranial base length (Ba-N) was found to be significantly smaller in the patient group (t = 10.04). The anterior cranial base length (S-N) was smaller to the same degree in the patient group (t = 6.51). The posterior component of the cranial base (S-Ar) was even less developed in the patient group (t = 12.65). We have to consider that the growth of this region is dependent upon the activity of the spheno-occipital synchondrosis, which is still present even after puberty. Mandible. The total length of the mandible (Ar-Pog) was found to be significantly smaller in the patient group (t = 8.45). Similarly, the length of the ramus (t = 5.94) and the length of the corpus (t = 7.60) were significantly smaller in the patient group. MaxiZZa. The length of the maxilla (ANS-PNS) was also found to be sma.ller
Familial
Fig.
Table and
I.
patients
Comparison with
of
3. Angular
cephalometric
the syndrome
dwarfism
and high @urna
Angles
dwarfism
between and
D.A.P. Ba-N S-N S-Ar Ar-Peg Ar-Go Go-Pog ANS-PNS A-PNS N-S-Ar SNA SNB Ar-Go-Gn FMA
plasma
normal
control
subjects
IR-HGH
Controla
(mm.1
2 S.D.
&lean (mm.1
173.0 84.7 58.1 19.1 75.2 29.2 52.6 38.9 36.4 126.1 74.4 69.3 135.4 36.0
11.43 4.52 4.09 2.13 5.88 5.45 5.89 3.57 3.60 10.69 2.22 3.16 8.93 4.69
176.1 99.0 68.5 32.3 102.3 43.3 73.3 52.4 47.5 125.3 80.5 77.2 123.3 25.4
Meam
(mm.)
high
(degTec8)
Patients
Diameter8
199
measurements.
measurements
of familial
IR-HGH
Statistical + S.D.
t
2.60 0 3.00 2.52 8.26 5.13 6.29 3.44 3.05 0.36 0.82 1.68 2.11 1.38
0.84 10.04 6.51 12.65 8.45 5.94 7.60 8.58 7.43 0.24 8.18 6.97 4.19 6.86
evaluation /
P(t) > < < < < < < < < > < < <
Petah-T&a,
Athalia
Pertzelan,
M.D.,**
and
Israel
I
n 1966, Laron, Pertzelan, and Mannheimer’ described a syndrome of familial dwarfism which was indistinguishable both clinically and in many of the laboratory findings from pituitary dwarfism but in which there were abnormally high plasma concentrations of immunoreactive human growth hormone (IR-HGH). The possibility was raised that in these cases the circulating growth hormone is biologically inactive but immunologically active. Additional clinical and laboratory findings in these and newly discovered patients, all of whom were of Jewish origin, were later reported. 2l 3 An increasing awareness of this syndrome led to the finding of several non-Jewish patients in other countries.3 One of the typical features of this syndrome is a small face and mandible, which gives the false impression of a large head (Fig. 1). Scharf anti Laron4 calculated the ratio between the bicondylar and biparietal diameters from anteroposterior roentgenograms of the skull and found t,hat they were significantly below normal values. The purpose of this investigation was to study the dimension and orientation From
the
Institute
of
Pediatric
and
Adolescent
Endocrinology,
Supported in part by a grant from the Faculty for Tel Aviv University. “Lecturer in Orthodontics, Faculty of Continuing School of Medicine, Tel Aviv University. **Senior Lecturer in Pediatrics, and Senior Assistant, Institute Hospital. ***Profewor University; Hospital; Health.
196
of
Sacklcr Pediatric
School and
Continuing Medical
Beilinson Medical Education,
of Medicine, Tel Aviv Adolescent Endocrinology,
of Pediatric Endocrinology, Sackler School of Medicine, Director, Institute of Pediatric and Adolescent Endocrinology, Established Investigator of the Chief Scientist’s Bureau,
Hospital. Education, Sackler University, Beilinson Tel Aviv Beilinson Ministry of
Familial
Fig.
1. The
age
7942
head
of
a male
patient
with
dwarfism
familial
and high plasma IR-HGH
dwarfism
and
high
plasma
IR-HGH
197
at
years.
of a number of the skeletal elements of the profile of these patients using lateral cephalometric head films. Materials
and
methods
For this study, ten lateral cephalograms of patients with the syndrome of familial dwarfism and high plasma IR-HGH were made under standardized conditions with the same cephalostat. They presented sufficient criteria for accurate measurements. The chronologic ages of the patients ranged from 9 to 18 years (three patients were 9 years old, two 11 years, one 13 years, one 14 years, two 16 years, and one 18 years old). For comparative purposes, a group of normal children and adolescents, matched for age and sex, were studied by the same methods. The following linear and angular measurements were taken in the patients and controls (Fig. 2). Linear measurements (in millimeters) 1. Anteroposterior head length : measured between the most prominent points in the forehead and back of the skull. distance between basion and nasion (Ba-N). 2. Total length of the cranial base: 3. Length of the anterior cranial base : sella-nasion (S-N). 4. Length of the posterior cranial base: sella-articulare ( S-Ar) . 5. Total length of the mandible: articulare-pogonion (Ar-Pog). 6. Length of the ramus of the mandible : articulare-gonion (Ar-G) . 7. Length of the corpus of the mandible : gonion-pogonion (Go-Pog). 8. Length of the maxilla: anterior nasal spine-posterior nasal spine (ANS-PNS). 9. Length of the maxillary apical base: subspinale-posterior nasal spine (A-PNS). Angular measurements (Fig. 3) S-N-A (sella-nasion-subspinale) : this angle measures the degree of maxillary prognathism.
Fig.
2. Linear
measurements.
S-N-B (sella-nasion-supramentale) : this angle shows the anterior limit of the mandibular basal arch in relation to the anterior cranial base. N-S-Ar (nasion-sella-articulare) : this cranial base angle indicates the degree of bending of the cranial base. angle determines the angulation between Ar-G-Gn (articulare-gonion-gnathion) : this the ramus and corpus of the mandible. angle is formed between the Frankfort FMA (Frankfort-mandibular angle) : this horizontal reference plane and the mandibular plane.
Head length. Statistically no significant difference was found in this measurement between the patients and the normal group (t = 0.84, p. > 0.1). Cranial base. The total cranial base length (Ba-N) was found to be significantly smaller in the patient group (t = 10.04). The anterior cranial base length (S-N) was smaller to the same degree in the patient group (t = 6.51). The posterior component of the cranial base (S-Ar) was even less developed in the patient group (t = 12.65). We have to consider that the growth of this region is dependent upon the activity of the spheno-occipital synchondrosis, which is still present even after puberty. Mandible. The total length of the mandible (Ar-Pog) was found to be significantly smaller in the patient group (t = 8.45). Similarly, the length of the ramus (t = 5.94) and the length of the corpus (t = 7.60) were significantly smaller in the patient group. MaxiZZa. The length of the maxilla (ANS-PNS) was also found to be sma.ller
Familial
Fig.
Table and
I.
patients
Comparison with
of
3. Angular
cephalometric
the syndrome
dwarfism
and high @urna
Angles
dwarfism
between and
D.A.P. Ba-N S-N S-Ar Ar-Peg Ar-Go Go-Pog ANS-PNS A-PNS N-S-Ar SNA SNB Ar-Go-Gn FMA
plasma
normal
control
subjects
IR-HGH
Controla
(mm.1
2 S.D.
&lean (mm.1
173.0 84.7 58.1 19.1 75.2 29.2 52.6 38.9 36.4 126.1 74.4 69.3 135.4 36.0
11.43 4.52 4.09 2.13 5.88 5.45 5.89 3.57 3.60 10.69 2.22 3.16 8.93 4.69
176.1 99.0 68.5 32.3 102.3 43.3 73.3 52.4 47.5 125.3 80.5 77.2 123.3 25.4
Meam
(mm.)
high
(degTec8)
Patients
Diameter8
199
measurements.
measurements
of familial
IR-HGH
Statistical + S.D.
t
2.60 0 3.00 2.52 8.26 5.13 6.29 3.44 3.05 0.36 0.82 1.68 2.11 1.38
0.84 10.04 6.51 12.65 8.45 5.94 7.60 8.58 7.43 0.24 8.18 6.97 4.19 6.86
evaluation /
P(t) > < < < < < < < < > < < <
