The Robinow An Isolated Case With
of the
a
Syndrome Study
Detailed
Phenotype
Thaddeus E. Kelly, MD; Robert Benson, MD; Samia Temtamy, MD, PhD; Leslie Plotnick, MD; L. Stefan Levin, DDS, MSD
A 13-year-old boy with the Robinow syndrome exhibited previously unreported anomalies of the digits, oral cavity, and middle ear. There was a marked phenotypic overlap between the Robinow syndrome and the Aarskog-Scott syndrome.
Robinow et al1 described mother and her three children with a syndrome characterized by mesomelic dwarfism, genital hypopla¬ sia, and distinctive facies. Additional
In 1969, a
recently reported by Wadlingal,2 Vera-Roman,1 Robinow,4 and Feingold and Bull5 have broad¬ ened the description of the phenotype of individuals with the syndrome and cases
ton et
have made the pattern of inheritance less clear." We report here the results of detailed studies of an additional case that showed marked digital, oral, and middle ear anomalies not previ¬ ously noted. REPORT OF A CASE The patient was first seen at the Johns Hopkins Hospital at 13 years of age for evaluation of short stature and genital hypoplasia. He was the product of a fullterm pregnancy of a 27-year-old, gravida 4, para 4 mother, and a 35-year-old unre¬ lated father. His birth weight was 2,950 gm (6.5 lb). Sex identity was initially un¬ certain because of bilateral cryptorchidism and micropenis. He was also noted to have a relatively large head, midfacial hypoReceived for publication March 25, 1974; accepted July 5. From the departments of pediatrics and medicine, Johns Hopkins University School of Medi-
cine, Baltimore. Reprint requests to John F. Kennedy Institute, 707 N Broadway, Baltimore, MD 21205 (Dr.
Kelly).
plasia, and unusual facies. No neonatal problems occurred, and initial growth and development were normal. The first deciduous tooth erupted at 7 months of age. The deciduous teeth failed to exfoliate normally, and several were ex¬ tracted to allow eruption of their perma¬ nent successors. The first permanent tooth did not erupt until 8 years of age. An umbilical hernia was repaired at 1 year of age. At 8 years of age, a five-week course of human chorionic gonadotropins (three injections weekly) failed to alter the cryptorchidism. However, it did lead to the appearance of pubic hair. At 9 years of age, he underwent myringotomies with in¬ sertion of polyethylene tubes for correction of a conductive hearing loss secondary to chronic serous otitis media. At 10 years of age,
a
right orchiorrhaphy
was unsuccess¬
ful due to vascular compromise of the tes¬ tis. At 11 years of age, a left orchiorrhaphy brought the testis to the upper part of the scrotum only. He performed on an age-ap¬ propriate level in school. The father was 178 cm (5 ft 11 inches) tall and the mother was 157.5 cm (5 ft 3 inches) tall. Siblings included a 20-year-old brother 178 cm (5 ft 11 inches) tall, a 17year-old sister 162.5 cm (5 ft 5 inches) tall, and a 15-year-old sister 167.5 cm (5 ft 7 inches) in height. None exhibited any fa¬ cial, digital, or genital anomalies and all were in good health.
Physical Examination At 13 years 2 months his height was 146.5 cm (4 ft 10% inches) (tenth percen¬ tile) and his weight 35.6 kg (78.5 lb) (tenth percentile). His arm span was 140 cm (4 ft 8 inches) (at 13 years of age, the arm span normally exceeds the height by 3 cm [1.2 inches]).' The upper segment measure¬ ment was 75.3 cm (30.1 inches) and the lower segment was 71 cm (28.4 inches),
Fig 1.—Patient
at 13 years of age.
with upper to lower segment ratio of 1.07 (at 13 years of age, the mean normal ratio is 0.97; the patient's ratio is increased due to a reduction in the lower segment rather than an increase in the upper).7 His head circumference was 55.3 cm (22.1 inches) and chest circumference 65 cm (26 inches). Pulse was 72 beats per minute; respiration, 20 per minute; and blood pressure, 110/65 mm
Hg.
The general appearance was that of a slender puberal boy with unusual facial features and anomalies of the hands, feet, and genitalia (Fig 1). Ocular hypertelorism was striking (Fig 2, left). The external intercanthal distance was 13.5 cm (5.4 inches), and the internal intercanthal dis¬ tance was 4.2 cm (1.7 inches). He had wide palpebrai fissures and a staring look. Visual acuity was normal, and funduscopic examination revealed megalopapillae bi¬ laterally. The nostrils were upturned. The philtrum was short and the upper lip was bow-shaped. The antihelices were unfolded and the external auditory canal teardropshaped (Fig 2, right). There was bilateral serous otitis media. The Eustachian tube orifices were stenotic. Oral examination revealed numerous re¬ tained deciduous teeth with permanent successors developing in the alveolus (Fig
3, top). The following permanent teeth
congenitally absent: an upper lateral incisor, the lower canines, both lower sec¬ ond premolare and first molars, and all the second molars. The hard palate was broad and intact. A small torus palatinus was were
Downloaded From: http://archpedi.jamanetwork.com/ by a New York University User on 06/01/2015
was a rudimentary uvula appeared cleft. The attached gingiva was fibrotic and enlarged primarily in the anterior regions (Fig 3, bottom). The mar¬ ginal gingiva was erythematous. The al¬ veolar ridges were broad. Dental arch form was square. Although occlusion was within normal limits, the anterior teeth were malaligned. Ankyloglossia was present. Oral hygiene was poor, and there were nu¬
present. There
that
merous
A
restored and carious teeth.
moderate, asymmetrical pectus
cavatum
was
ex¬
present. Examination of the
heart revealed an ejection click along the left sternal border, and a grade 1-2/6 short, early systolic murmur along the up¬ per part of the left sternal border. The peripheral pulses were normal. Results of an abdominal examination were normal, apart from the scars of previous surgery. Results of the neurological examination were normal, apart from a hearing loss. Sexual development revealed Tanner stage 3 pubic hair" with no axillary hair or acne. The penis measured 5.0 cm (2 inches) in stretched length and was 2.5 cm (1 inch) in diameter. The urethral orifice was nor¬ mally placed. The right testis was intrascrotal and atrophie, while the left testis was in the inguinal canal and mea¬ sured approximately 2.0x1.0 cm (0.8x0.4
inches).
The upper limbs were short, with limita¬ tion of full extension and supination of the elbows. The hand malformation was bilat¬ eral and almost symmetrical. The hands were broad and short with short fingers, especially the index, ring, and little fingers (Fig 4, top). The terminal phalanges were
Fig 2.—Left, Ocular hypertelorism,
widened
short and bulbous. The thumbs were broad and had bifid nails. The interphalangeal joint of the thumb was inflexible. The nails of the index and little fingers were partic¬ ularly short, more so on the left. Mild web¬ bing was noted between the ring and little fingers. When the fingers were extended, hyperextension of the proximal inter¬ phalangeal joint and mild flexion of the distal phalanges were noted (Fig 4, bot¬ tom). He had broad feet with short, widely spaced toes and bulbous terminal pha¬ langes, particularly the great toe. Hand dermatoglyphics showed normal transverse creases, digital triradii, and normal level of axial triradius. He had a whorl thenar pattern on the left hand. The fingerprint pattern showed arches on all fingers and an ulnar loop on both thumbs. He had a single flexion crease on the ring and little fingers. The feet showed a whorl hallucal pattern.
tive hearing loss, mild on the left and mod¬ erate on the right. The electrocardiogram was normal. An echocardiogram showed questionably en¬ larged aorta with three aortic valve leaf¬ lets. The phonocardiogram confirmed the ejection click and an early systolic ejection murmur.
Skeletal
roentgenograms revealed
a
slight increase
in bone density. The bones tended to be short and wide. Roentgen¬ ograms of the skull disclosed ocular hyper¬ telorism with an interorbital distance of 37 mm (1.5 inches). There was a mild scoliosis convex to the left at L-4 and to the right at T-7. There were no hemivertebrae. How-
Laboratory Data Results of routine urinalysis, hemogram, and blood chemistry tests were normal. Urinary screening revealed no mucopolysaccharides, reducing substances, or keto acids. Urinary amino acid screening was normal. Serum IgG, IgM, and IgA were within the normal range for age. Plasma testosterone was 61 ng/100 ml; luteinizing hormone, 55 ng/ml; and follicle-stimulate ing hormone, 316 ng/ml (all are within the normal range for early puberal boys). Wechsler Intelligence scores were as fol¬ lows: verbal intelligence quotient, 93; per¬ formance IQ, 94; and full scale IQ, 93. Audiograms revealed a bilateral conduc-
palpebrai fissures. Right, Lateral view of face.
Fig 3.—Top, Panorex showing retained deciduous teeth, unerupted permanent teeth, and congenially missing teeth. Bot¬ tom, Anterior oral cavity showing malalignment of teeth and hyperplastic gingiva.
Fig 4.—Top, gers.
Broad hands with short fin¬
Bottom, Hyperextension of proximal
interphalangeal joints.
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a spina bifida occulta at C-5 was iden¬ tified. The humeri and radii had lengths equal to the mean for a 10% year old boy (Maresh standards). Moderate flaring of the epiphyses was noted in the upper and lower limbs. Hand roentgenograms showed shortening of all bones with selec¬ tive malformations of certain phalanges (Fig 5, left). The distal phalanx of the thumb was broad and bifid in its distal two thirds. The distal phalanges of the index and little fingers were short, with ulnar de¬ viation of the distal phalanx of the index finger. The middle phalanges of the lit¬ tle fingers were also short, and their epi¬ physes were absent. In the feet, the distal phalanges of both big toes were scalloped and the remaining toes contained only two phalanges (Fig 5, right). At a chronological age of 12 years 7 months, the bone age was 13 years 4 months. Stenver view and temporal bone tomog¬ raphy disclosed markedly sclerotic mastoids, small internal auditory canals, con¬ tracture of the middle ear space, and displacement of the carotid artery and jugular vein.
ever,
COMMENT
Our
patient had most of the fea¬ tures diagnostic of the Robinow syn¬ drome: brachymesomelic dwarfism, characteristic facies, and genital hypoplasia. He also had some find¬ ings noted in cases of the AarskogScott syndrome.912 Detailed study of his phenotype showed other malfor¬ mations not previously reported in ei¬ ther the Robinow or Aarskog-Scott syndromes. These abnormalities were in the fingers, oral cavity, and middle ear. Analysis of the main features of the Robinow syndrome, the AarskogScott syndrome, and our patient are
pothesis. The Aarskog-Scott
syn¬ drome is considered an X-linked recessive disorder with variable expression in the female. Autosomal dominant inheritance with only par¬ tial expression in affected females has been suggested by Sugarman et al.12 The oral findings in previously re¬ ported cases of the Robinow syn-
drome have not been well defined. Wadlington et al2 reported irregular and crowded teeth in their cases. In addition, one of their patients did not lose any teeth until he was 8 years old (W.B. Wadlington, MD, written com¬ munication, September 1974). Feingold and Bull5 noted gingival hyper¬ plasia in their patient, an infant. The
Comparison of Main Phenotypic Characteristics of Robinow Syndrome, Aarskog-Scott Syndrome, and Present Case Aarskog-Scott +
Stature: short Facies
+
Hypertelorism
Wide palpebrai fissures Ptosis
+ +
Robinow +
Present Case
+ +
+ 4-
—
—
+
—
Long philtrum
Bow or inverted V-shaped upper lip Widow's peak Oral manifestations Dental malocclusion Dental malalignment Mandibular hypoplasia
—
—
+
+
—
—
+ —
+
?
?
+ +
—
Maxillary hypoplasia
Hyperplastic gingivae Congenially absent teeth Delayed exfoliation of
+
?
?
+ ?
+ —
+ + + —
—
?
deciduous teeth
Ankyloglossia Cleft lip/palate
+
-f
—(1 case)
Abnormal uvula Digital malformations Short hands with short or incurved fifth finger Single flexion crease on little finger Single flexion crease on other fingers Short distal phalanges
+ +
—
+
+
+
+
—
—
—
+
+
+ —
+
—
-f
—
+ +
_
Fig 5.—Left, Roentgenographic features of hand malformations. Right, Phalangeal changes in feet.
shown in the Table. There is a marked phenotypic overlap between these two syndromes as well as between the two syndromes and our patient. Gen¬ ital hypoplasia in the Robinow syn¬ drome and saddle scrotum deformity in the Aarskog-Scott syndrome seem to currently be the major differ¬ entiating features. The pattern of in¬ heritance may also be different. The pattern in the original family re¬ ported by Robinow was consistent with an autosomal or X-linked domi¬ nant gene.1 Our case presumably is the result of a new dominant muta¬ tion, the relatively advanced paternal age being consistent with this hy-
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gingival enlargement seen in our pa¬ tient may be due to poor oral hygiene. However, it is equally possible that this finding may represent one of the pleiotropic effects of the mutant gene. Gingival hyperplasia has been re¬ ported as a component of several other syndromes.13 Oral findings have not been described in detail in re-
ported cases of the Aarskog-Scott syndrome. Complete descriptions of such findings in future cases of these two syndromes will further define the spectrum of oral changes, and may
to further differentiate them. In the absence of biochemical char¬ acterization of the Robinow syn¬ drome, further detailed clinical and serve
genetic studies
are
needed for
curate delineation of the
an ac¬
syndrome.
This investigation was supported by Maternal and Child Health Services grant 917 (Dr. Kelly), National Foundation postdoctoral fellowship in medical genetics (Dr. Temtamy), Public Health Service grant 5-T01-AM-05219-14 (Drs. Benson and Plotnick), and National Institute of Dental Research grant 5-T01-DE00193 (Dr. Levin).
References 1. Robinow M, Silverman FN, Smith HG: A newly recognized dwarfing syndrome. Am J Dis Child 117:645-651, 1969. 2. Wadlington WB, Tucker VL, Schimke RN: Mesomelic dwarfism with hemivertebrae and small genitalia (the Robinow syndrome). Am J Dis Child 126:202\x=req-\ 205, 1973. 3. Vera-Roman JM: Robinow dwarfism
syndrome accompanied by penile agenesis and hemivertebrae. Am J Dis Child 126:206-208, 1973. 4. Robinow M: Fetal face syndrome, in Bergsma D (ed): Birth Defects Atlas and Compendium. Baltimore, Williams & Wil-
kins Co, 1973, pp 410-411.
5.
Feingold M, Bull M: Syndrome Identi-
fication.
D Bergsma (ed), White Plains, NY, National Foundation-March of Dimes, 1973, pp 14-16. 6. Robinow M: A syndrome's progress. Am J Dis Child 126:150, 1973. 7. Wilkins LW: The Diagnosis and Treatment of Endocrine Disorders in Childhood and Adolescence, ed 3. Springfield, Ill, Charles C Thomas Publisher, 1965, p 33. 8. Tanner JM: Growth at Adolescence, ed 2, Oxford, England, Blackwell Scientific Publications, 1962. 9. Aarskog D: A familial syndrome of short stature associated with facial dys-
Second
Thoughts
on
Medical
Writing:
plasia and genital anomalies. Birth Defects 7(pt 10):235-239, 1971. 10. Scott CI: Unusual facies, joint hyperextensibility, genital anomaly and short stature: A new dysmorphic syndrome. Birth Defects 7(pt 10):240-246, 1971. 11. Furukawa CT, Hall BD, Smith DW: The Aarskog syndrome. J Pediatr 81:1117\x=req-\ 1122, 1972. 12. Sugarman GI, Rimoin DL, Lachman RS: The facial-digital-genital (Aarskog) syndrome. Am J Dis Child 126:248-252, 1973. 13. Witkop CJ Jr: Heterogeneity in gingival fibromatosis. Birth Defects 7(pt 11):210-221, 1971.
III.
Inexperienced medical writers often prejudice editorial judgment adversely, and un¬ necessarily, by simple carelessness. Writing that may have merit enough to rate a re¬ viewer's grade of 3 (accept if suitably revised) may easily be dragged down to one of U (publish only if needed to fill space) because its writer neglected to do the following: 1. Read the directions. Every journal has its "Preparation of Manuscripts" page, giv¬ ing simple instructions as to the name and address of the present editor, the size and grade of paper to be used, the style and order of reference citations, and the prepara¬ tion of illustrations and tables. If such a page is lost among the present flood of adver¬ tisements, a writer should at least compare the reference citation format in the journal at which he aims with that in his paper. (Failure to do so has been known to lead to re¬ sults arousing editorial suspicion that the manuscript was prepared for and rejected by another journal.) 2. Employ a typist who can type neatly, spell correctly, and punctuate properly, but also 3. Proofread everything, if possible in a medical library where the references (a fa¬ vorite hunting ground of touchy reviewers) can be checked for accuracy. A single error may not affect reviewer or editorial ratings. Enough of them can. Re¬ viewers and editors are by nature and experience appreciative of accuracy and pre¬ cision. And they are often too fatigued by their nocturnal paper work to forgive those who make it harder. C. A. Smith
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of the
a
Syndrome Study
Detailed
Phenotype
Thaddeus E. Kelly, MD; Robert Benson, MD; Samia Temtamy, MD, PhD; Leslie Plotnick, MD; L. Stefan Levin, DDS, MSD
A 13-year-old boy with the Robinow syndrome exhibited previously unreported anomalies of the digits, oral cavity, and middle ear. There was a marked phenotypic overlap between the Robinow syndrome and the Aarskog-Scott syndrome.
Robinow et al1 described mother and her three children with a syndrome characterized by mesomelic dwarfism, genital hypopla¬ sia, and distinctive facies. Additional
In 1969, a
recently reported by Wadlingal,2 Vera-Roman,1 Robinow,4 and Feingold and Bull5 have broad¬ ened the description of the phenotype of individuals with the syndrome and cases
ton et
have made the pattern of inheritance less clear." We report here the results of detailed studies of an additional case that showed marked digital, oral, and middle ear anomalies not previ¬ ously noted. REPORT OF A CASE The patient was first seen at the Johns Hopkins Hospital at 13 years of age for evaluation of short stature and genital hypoplasia. He was the product of a fullterm pregnancy of a 27-year-old, gravida 4, para 4 mother, and a 35-year-old unre¬ lated father. His birth weight was 2,950 gm (6.5 lb). Sex identity was initially un¬ certain because of bilateral cryptorchidism and micropenis. He was also noted to have a relatively large head, midfacial hypoReceived for publication March 25, 1974; accepted July 5. From the departments of pediatrics and medicine, Johns Hopkins University School of Medi-
cine, Baltimore. Reprint requests to John F. Kennedy Institute, 707 N Broadway, Baltimore, MD 21205 (Dr.
Kelly).
plasia, and unusual facies. No neonatal problems occurred, and initial growth and development were normal. The first deciduous tooth erupted at 7 months of age. The deciduous teeth failed to exfoliate normally, and several were ex¬ tracted to allow eruption of their perma¬ nent successors. The first permanent tooth did not erupt until 8 years of age. An umbilical hernia was repaired at 1 year of age. At 8 years of age, a five-week course of human chorionic gonadotropins (three injections weekly) failed to alter the cryptorchidism. However, it did lead to the appearance of pubic hair. At 9 years of age, he underwent myringotomies with in¬ sertion of polyethylene tubes for correction of a conductive hearing loss secondary to chronic serous otitis media. At 10 years of age,
a
right orchiorrhaphy
was unsuccess¬
ful due to vascular compromise of the tes¬ tis. At 11 years of age, a left orchiorrhaphy brought the testis to the upper part of the scrotum only. He performed on an age-ap¬ propriate level in school. The father was 178 cm (5 ft 11 inches) tall and the mother was 157.5 cm (5 ft 3 inches) tall. Siblings included a 20-year-old brother 178 cm (5 ft 11 inches) tall, a 17year-old sister 162.5 cm (5 ft 5 inches) tall, and a 15-year-old sister 167.5 cm (5 ft 7 inches) in height. None exhibited any fa¬ cial, digital, or genital anomalies and all were in good health.
Physical Examination At 13 years 2 months his height was 146.5 cm (4 ft 10% inches) (tenth percen¬ tile) and his weight 35.6 kg (78.5 lb) (tenth percentile). His arm span was 140 cm (4 ft 8 inches) (at 13 years of age, the arm span normally exceeds the height by 3 cm [1.2 inches]).' The upper segment measure¬ ment was 75.3 cm (30.1 inches) and the lower segment was 71 cm (28.4 inches),
Fig 1.—Patient
at 13 years of age.
with upper to lower segment ratio of 1.07 (at 13 years of age, the mean normal ratio is 0.97; the patient's ratio is increased due to a reduction in the lower segment rather than an increase in the upper).7 His head circumference was 55.3 cm (22.1 inches) and chest circumference 65 cm (26 inches). Pulse was 72 beats per minute; respiration, 20 per minute; and blood pressure, 110/65 mm
Hg.
The general appearance was that of a slender puberal boy with unusual facial features and anomalies of the hands, feet, and genitalia (Fig 1). Ocular hypertelorism was striking (Fig 2, left). The external intercanthal distance was 13.5 cm (5.4 inches), and the internal intercanthal dis¬ tance was 4.2 cm (1.7 inches). He had wide palpebrai fissures and a staring look. Visual acuity was normal, and funduscopic examination revealed megalopapillae bi¬ laterally. The nostrils were upturned. The philtrum was short and the upper lip was bow-shaped. The antihelices were unfolded and the external auditory canal teardropshaped (Fig 2, right). There was bilateral serous otitis media. The Eustachian tube orifices were stenotic. Oral examination revealed numerous re¬ tained deciduous teeth with permanent successors developing in the alveolus (Fig
3, top). The following permanent teeth
congenitally absent: an upper lateral incisor, the lower canines, both lower sec¬ ond premolare and first molars, and all the second molars. The hard palate was broad and intact. A small torus palatinus was were
Downloaded From: http://archpedi.jamanetwork.com/ by a New York University User on 06/01/2015
was a rudimentary uvula appeared cleft. The attached gingiva was fibrotic and enlarged primarily in the anterior regions (Fig 3, bottom). The mar¬ ginal gingiva was erythematous. The al¬ veolar ridges were broad. Dental arch form was square. Although occlusion was within normal limits, the anterior teeth were malaligned. Ankyloglossia was present. Oral hygiene was poor, and there were nu¬
present. There
that
merous
A
restored and carious teeth.
moderate, asymmetrical pectus
cavatum
was
ex¬
present. Examination of the
heart revealed an ejection click along the left sternal border, and a grade 1-2/6 short, early systolic murmur along the up¬ per part of the left sternal border. The peripheral pulses were normal. Results of an abdominal examination were normal, apart from the scars of previous surgery. Results of the neurological examination were normal, apart from a hearing loss. Sexual development revealed Tanner stage 3 pubic hair" with no axillary hair or acne. The penis measured 5.0 cm (2 inches) in stretched length and was 2.5 cm (1 inch) in diameter. The urethral orifice was nor¬ mally placed. The right testis was intrascrotal and atrophie, while the left testis was in the inguinal canal and mea¬ sured approximately 2.0x1.0 cm (0.8x0.4
inches).
The upper limbs were short, with limita¬ tion of full extension and supination of the elbows. The hand malformation was bilat¬ eral and almost symmetrical. The hands were broad and short with short fingers, especially the index, ring, and little fingers (Fig 4, top). The terminal phalanges were
Fig 2.—Left, Ocular hypertelorism,
widened
short and bulbous. The thumbs were broad and had bifid nails. The interphalangeal joint of the thumb was inflexible. The nails of the index and little fingers were partic¬ ularly short, more so on the left. Mild web¬ bing was noted between the ring and little fingers. When the fingers were extended, hyperextension of the proximal inter¬ phalangeal joint and mild flexion of the distal phalanges were noted (Fig 4, bot¬ tom). He had broad feet with short, widely spaced toes and bulbous terminal pha¬ langes, particularly the great toe. Hand dermatoglyphics showed normal transverse creases, digital triradii, and normal level of axial triradius. He had a whorl thenar pattern on the left hand. The fingerprint pattern showed arches on all fingers and an ulnar loop on both thumbs. He had a single flexion crease on the ring and little fingers. The feet showed a whorl hallucal pattern.
tive hearing loss, mild on the left and mod¬ erate on the right. The electrocardiogram was normal. An echocardiogram showed questionably en¬ larged aorta with three aortic valve leaf¬ lets. The phonocardiogram confirmed the ejection click and an early systolic ejection murmur.
Skeletal
roentgenograms revealed
a
slight increase
in bone density. The bones tended to be short and wide. Roentgen¬ ograms of the skull disclosed ocular hyper¬ telorism with an interorbital distance of 37 mm (1.5 inches). There was a mild scoliosis convex to the left at L-4 and to the right at T-7. There were no hemivertebrae. How-
Laboratory Data Results of routine urinalysis, hemogram, and blood chemistry tests were normal. Urinary screening revealed no mucopolysaccharides, reducing substances, or keto acids. Urinary amino acid screening was normal. Serum IgG, IgM, and IgA were within the normal range for age. Plasma testosterone was 61 ng/100 ml; luteinizing hormone, 55 ng/ml; and follicle-stimulate ing hormone, 316 ng/ml (all are within the normal range for early puberal boys). Wechsler Intelligence scores were as fol¬ lows: verbal intelligence quotient, 93; per¬ formance IQ, 94; and full scale IQ, 93. Audiograms revealed a bilateral conduc-
palpebrai fissures. Right, Lateral view of face.
Fig 3.—Top, Panorex showing retained deciduous teeth, unerupted permanent teeth, and congenially missing teeth. Bot¬ tom, Anterior oral cavity showing malalignment of teeth and hyperplastic gingiva.
Fig 4.—Top, gers.
Broad hands with short fin¬
Bottom, Hyperextension of proximal
interphalangeal joints.
Downloaded From: http://archpedi.jamanetwork.com/ by a New York University User on 06/01/2015
a spina bifida occulta at C-5 was iden¬ tified. The humeri and radii had lengths equal to the mean for a 10% year old boy (Maresh standards). Moderate flaring of the epiphyses was noted in the upper and lower limbs. Hand roentgenograms showed shortening of all bones with selec¬ tive malformations of certain phalanges (Fig 5, left). The distal phalanx of the thumb was broad and bifid in its distal two thirds. The distal phalanges of the index and little fingers were short, with ulnar de¬ viation of the distal phalanx of the index finger. The middle phalanges of the lit¬ tle fingers were also short, and their epi¬ physes were absent. In the feet, the distal phalanges of both big toes were scalloped and the remaining toes contained only two phalanges (Fig 5, right). At a chronological age of 12 years 7 months, the bone age was 13 years 4 months. Stenver view and temporal bone tomog¬ raphy disclosed markedly sclerotic mastoids, small internal auditory canals, con¬ tracture of the middle ear space, and displacement of the carotid artery and jugular vein.
ever,
COMMENT
Our
patient had most of the fea¬ tures diagnostic of the Robinow syn¬ drome: brachymesomelic dwarfism, characteristic facies, and genital hypoplasia. He also had some find¬ ings noted in cases of the AarskogScott syndrome.912 Detailed study of his phenotype showed other malfor¬ mations not previously reported in ei¬ ther the Robinow or Aarskog-Scott syndromes. These abnormalities were in the fingers, oral cavity, and middle ear. Analysis of the main features of the Robinow syndrome, the AarskogScott syndrome, and our patient are
pothesis. The Aarskog-Scott
syn¬ drome is considered an X-linked recessive disorder with variable expression in the female. Autosomal dominant inheritance with only par¬ tial expression in affected females has been suggested by Sugarman et al.12 The oral findings in previously re¬ ported cases of the Robinow syn-
drome have not been well defined. Wadlington et al2 reported irregular and crowded teeth in their cases. In addition, one of their patients did not lose any teeth until he was 8 years old (W.B. Wadlington, MD, written com¬ munication, September 1974). Feingold and Bull5 noted gingival hyper¬ plasia in their patient, an infant. The
Comparison of Main Phenotypic Characteristics of Robinow Syndrome, Aarskog-Scott Syndrome, and Present Case Aarskog-Scott +
Stature: short Facies
+
Hypertelorism
Wide palpebrai fissures Ptosis
+ +
Robinow +
Present Case
+ +
+ 4-
—
—
+
—
Long philtrum
Bow or inverted V-shaped upper lip Widow's peak Oral manifestations Dental malocclusion Dental malalignment Mandibular hypoplasia
—
—
+
+
—
—
+ —
+
?
?
+ +
—
Maxillary hypoplasia
Hyperplastic gingivae Congenially absent teeth Delayed exfoliation of
+
?
?
+ ?
+ —
+ + + —
—
?
deciduous teeth
Ankyloglossia Cleft lip/palate
+
-f
—(1 case)
Abnormal uvula Digital malformations Short hands with short or incurved fifth finger Single flexion crease on little finger Single flexion crease on other fingers Short distal phalanges
+ +
—
+
+
+
+
—
—
—
+
+
+ —
+
—
-f
—
+ +
_
Fig 5.—Left, Roentgenographic features of hand malformations. Right, Phalangeal changes in feet.
shown in the Table. There is a marked phenotypic overlap between these two syndromes as well as between the two syndromes and our patient. Gen¬ ital hypoplasia in the Robinow syn¬ drome and saddle scrotum deformity in the Aarskog-Scott syndrome seem to currently be the major differ¬ entiating features. The pattern of in¬ heritance may also be different. The pattern in the original family re¬ ported by Robinow was consistent with an autosomal or X-linked domi¬ nant gene.1 Our case presumably is the result of a new dominant muta¬ tion, the relatively advanced paternal age being consistent with this hy-
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gingival enlargement seen in our pa¬ tient may be due to poor oral hygiene. However, it is equally possible that this finding may represent one of the pleiotropic effects of the mutant gene. Gingival hyperplasia has been re¬ ported as a component of several other syndromes.13 Oral findings have not been described in detail in re-
ported cases of the Aarskog-Scott syndrome. Complete descriptions of such findings in future cases of these two syndromes will further define the spectrum of oral changes, and may
to further differentiate them. In the absence of biochemical char¬ acterization of the Robinow syn¬ drome, further detailed clinical and serve
genetic studies
are
needed for
curate delineation of the
an ac¬
syndrome.
This investigation was supported by Maternal and Child Health Services grant 917 (Dr. Kelly), National Foundation postdoctoral fellowship in medical genetics (Dr. Temtamy), Public Health Service grant 5-T01-AM-05219-14 (Drs. Benson and Plotnick), and National Institute of Dental Research grant 5-T01-DE00193 (Dr. Levin).
References 1. Robinow M, Silverman FN, Smith HG: A newly recognized dwarfing syndrome. Am J Dis Child 117:645-651, 1969. 2. Wadlington WB, Tucker VL, Schimke RN: Mesomelic dwarfism with hemivertebrae and small genitalia (the Robinow syndrome). Am J Dis Child 126:202\x=req-\ 205, 1973. 3. Vera-Roman JM: Robinow dwarfism
syndrome accompanied by penile agenesis and hemivertebrae. Am J Dis Child 126:206-208, 1973. 4. Robinow M: Fetal face syndrome, in Bergsma D (ed): Birth Defects Atlas and Compendium. Baltimore, Williams & Wil-
kins Co, 1973, pp 410-411.
5.
Feingold M, Bull M: Syndrome Identi-
fication.
D Bergsma (ed), White Plains, NY, National Foundation-March of Dimes, 1973, pp 14-16. 6. Robinow M: A syndrome's progress. Am J Dis Child 126:150, 1973. 7. Wilkins LW: The Diagnosis and Treatment of Endocrine Disorders in Childhood and Adolescence, ed 3. Springfield, Ill, Charles C Thomas Publisher, 1965, p 33. 8. Tanner JM: Growth at Adolescence, ed 2, Oxford, England, Blackwell Scientific Publications, 1962. 9. Aarskog D: A familial syndrome of short stature associated with facial dys-
Second
Thoughts
on
Medical
Writing:
plasia and genital anomalies. Birth Defects 7(pt 10):235-239, 1971. 10. Scott CI: Unusual facies, joint hyperextensibility, genital anomaly and short stature: A new dysmorphic syndrome. Birth Defects 7(pt 10):240-246, 1971. 11. Furukawa CT, Hall BD, Smith DW: The Aarskog syndrome. J Pediatr 81:1117\x=req-\ 1122, 1972. 12. Sugarman GI, Rimoin DL, Lachman RS: The facial-digital-genital (Aarskog) syndrome. Am J Dis Child 126:248-252, 1973. 13. Witkop CJ Jr: Heterogeneity in gingival fibromatosis. Birth Defects 7(pt 11):210-221, 1971.
III.
Inexperienced medical writers often prejudice editorial judgment adversely, and un¬ necessarily, by simple carelessness. Writing that may have merit enough to rate a re¬ viewer's grade of 3 (accept if suitably revised) may easily be dragged down to one of U (publish only if needed to fill space) because its writer neglected to do the following: 1. Read the directions. Every journal has its "Preparation of Manuscripts" page, giv¬ ing simple instructions as to the name and address of the present editor, the size and grade of paper to be used, the style and order of reference citations, and the prepara¬ tion of illustrations and tables. If such a page is lost among the present flood of adver¬ tisements, a writer should at least compare the reference citation format in the journal at which he aims with that in his paper. (Failure to do so has been known to lead to re¬ sults arousing editorial suspicion that the manuscript was prepared for and rejected by another journal.) 2. Employ a typist who can type neatly, spell correctly, and punctuate properly, but also 3. Proofread everything, if possible in a medical library where the references (a fa¬ vorite hunting ground of touchy reviewers) can be checked for accuracy. A single error may not affect reviewer or editorial ratings. Enough of them can. Re¬ viewers and editors are by nature and experience appreciative of accuracy and pre¬ cision. And they are often too fatigued by their nocturnal paper work to forgive those who make it harder. C. A. Smith
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