Hallermann-Streiff Syndrome

Clinical and Prognostic Considerations

MAJ Russell W. Steele, MC, USA, and LTC James W. Bass, MC, USA, Honolulu

A patient with the Hallermann-Streiff syn- 40 weeks. The prenatal course, labor, and wise within normal limits for age. Chro¬
drome showed significant findings, in- delivery were uneventful and the infant's mosomal analysis by peripheral leukocyte
cluding demonstration of decreased thora- Apgar score at birth was 7, with respira¬ culture revealed a normal male chromo¬
cic compliance and a marked response of tion being established immediately. some complement (46 XY).
growth hormone to arginine stimulation. Physical examination at birth revealed Roentgenograms of the skull showed
No metabolic or chromosomal defect could a low birth weight male infant in no dis¬ absence of the angle of the mandible,
be demonstrated in this patient. tress. His length was 45.7 cm (18% inch¬ widely separated sutures, large fonta¬
es); his head circumference was 30.5 cm nelles, extremely thin cortex of the skull,
(12 inches); and his chest circumference and wormian bones in the parietal areas
combination of clinical findings
was25.4 cm (IOV2 inches). The crown to sym- bilaterally (Fig 4). Skeletal survey re¬
A now most commonly called the
Hallermann-Streiff syndrome in the
physis pubis/symphysis pubis to heel (U/L)
ratio was 1.79. The length to arm span ra¬
tio was 1.04. Of note, were dyscephaly
vealed hypoplastic ribs and clavicles, par¬
ticularly at the acromial ends (Fig 5).
There was shortening of the first meta-
American literature and the dysce- with bird facies, micrognathia, and glos- carpal bilaterally. The cardiothoracic ratio
soptosis (Fig 1 to 3). The cranial sutures was 0.65, and the cardiac configuration
phalic syndrome of Francois in the including the metopic and squamosal were was unusual (Fig 5).
European literature consists of the widely separated, and the fontanelles At 8 weeks of age, a routine follow-up
following: (1) dyscephaly with bird were large. Frontal and occipital bossing skeletal survey revealed a fracture of the
facies and hypoplastic mandible, (2) and craniotabes were noted. Skin over the left radius. There was no history of even
proportionate nanism, (3) congenital scalp was atrophie, and there was hypo- minor trauma. This healed without resid¬
trichosis of the scalp, eyelashes, and eye¬ ua. At 3 months of age, an intumescent
cataracts, (4) microphthalmia, (5) brows (Fig 1 and 2). There was striking
hypotrichosis, (6) dental anomalies, microphthalmia with a corneal diameter Fig 1.—Patient, age 7 months, Bird
(7) cutaneous atrophy, limited to the of 7 mm, and the eyes also appeared prop- fades, micrognathia, high U/L ratio,
face and/or scalp, (8) frontal or oc¬ totic; sclerae were blue and funduscopy small chest with pectus excavatum defor¬
cipital bossing, (9) open sutures and was normal. The nose was thin and beak¬ mity.
like with marked cutaneous atrophy (Fig
fontanelles, (10) high arched palate, 1 to 3). There was a small midline cleft of
and (11) nystagmus. Francois consid¬ the lower lip and a high arched grooved
ers the first seven features essential.1 palate. A natal tooth in the No. 24 posi¬
However, like many such syndromes, tion was present. The chest was relatively
reported cases frequently do not small, and there was a mild pectus ex-
demonstrate all manifestations. cavatum deformity (Fig 1); respirations
appeared shallow, and the respiratory
Moreover, nanism was not men¬ rate was 44 per minute. Auscultation of
tioned in one of the two original the lungs and heart was unremarkable.
patients described by Hallermann.2 Examination of the hands demonstrated
shortening of both thumbs.
The father was 167.6 cm (5 ft 6 inches)
Report of a Case and the mother was 165.1 (5 ft 5 inches).
This male infant weighed 2.3 kg (5 lb Neither exhibited any of the clinical fea¬
\lk oz) at birth and was born to a 22-year- tures noted in the infant and there was no
old, gravida 1, para 0, white mother and a family history of this condition.
24-year-old white father who deny con¬ Results of laboratory studies at birth,
sanguinity. The length of gestation was including hemogram, serum electrolytes,
calcium, phosphorus, glucose, alkaline
Received for publication May 15, 1970.
phosphatase, urea nitrogen and Venereal
From the Pediatric Service, Department of Disease Research Laboratory test were
Medicine, US Army Tripler General Hospital within normal limits. Urinalysis was nor¬
(Drs. Steele and Bass), and the Section of Pe- mal and the ferric chloride test on the
diatrics, University of Hawaii School of Medi- urine was negative. Urinary mucopoly-
cine (Dr. Steele), Honolulu.
Reprint requests to Pediatric Service, US saccharides, calcium, and phosphorus were
Army Tripler General Hospital, Honolulu, APO within normal limits for age. Quantitative
San Francisco 96438 (Dr. Steele). serum and urinary amino acids were like-

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 Fig 2.—Front view. Bird fades, hypo- Fig 3—Side view. Bird fades, %hypo-
plastic mandible, congenital cataracts, plastic mandible, hypotrichosis.
microphthalmia, hypotrichosis, frontal
and occipital bossing, glossoptosis, cuta¬
neous atrophy over nose.

cataract was first noted in the left eye, steroids, and mucopolysaccharides were
and at 6 months a similar defect involved within normal limits for age. Quantitative Fig 4.—Lateral roentgenogram of skull
at birth. Absence of angle of mandible,
the right eye. The right cataract was aspi¬ serum and urinary amino acid studies
rated at 8 months, and the left was sim¬ were again obtained, and results were
widely separated sutures, large fonta-
nels, thin cortex of skull.
ilarly aspirated at 11 months. At 5 months within normal limits for age. Growth hor¬
of age thepatient developed gradually in¬ mone assay with arginine stimulation in¬
creasing tachypnea, tachycardia, and creased from 5 ng units to 33 at two hours Fig 5.—Chest roentgenogram at birth.
hepatosplenomegaly. Auscultation of the after infusion. Hypoplastic ribs and clavicles, cardio-
thoracic ratio 0.65, with unusual cardiac
heart wasstill unremarkable. The electro¬ At 13 months of age the height was 58.4
cardiogram indicated biventricular hyper¬ cm (23V2 inches), and the weight was 4.9
configuration.
trophy, but neither the size nor kg (10 lb 13 oz). Bone age at this time was
configuration of the heart had changed on 6 to 9 months.
roentgenogram from birth. The patient
was believed to have congestive heart Comment
failure, so digitalization was initiated
with a very gradual response noted dur¬ Our survey of the American and
ing the following two weeks; however, European literature yielded 50 prob¬
hepatomegaly persisted for two months. able cases of Hallermann-Streiff syn¬
At 7 months of age, a right sided cardi¬ drome. The reported clinical findings
ac catheterization was performed. No
are summarized in Table l.1-"* There
anatomic defects were demonstrated, but
has been no similar review since the
emptying of the left ventricle appeared to
be marginally suboptimal with an esti¬ 21 cases collected by Francois in
mated ejection fraction of 50% to 60%. 1958.19
Also, decreased compliance of the thorax The present case demonstrates al¬
or intrathoracic structures was suggested
most all of the clinical and roentgen¬ been a contributory factor in the de¬
by wide respiratory variations on pres¬
sure tracings. ographic manifestations of this syn¬ velopment of pulmonary infection
At 9 months of age, results of the fol¬ drome. Numerous laboratory studies causing the early death reported in
lowing studies were normal; hemogram, failed to reveal the presence of any cases 49 and 50 and necessitating
serum electrolytes, calcium, phosphorus, metabolic abnormality; however, two tracheostomy in cases 30 and 34.
glucose, alkaline phosphatase, acid findings are of interest. Plasma The difficulty in evaluating this
phosphatase, blood urea nitrogen, cre¬
atinine, total serum protein and albumin- growth hormone was markedly ele¬ syndrome from reported cases is that
globulin ratio, total serum bilirubin, se¬ vated following arginine infusion. there is no specific clinical or labora¬
rum glutamic oxaloacetic transaminase, This observation demonstrates that tory test to categorize definitely
lactic acid dehydrogenase, creatinine the patient did not have a deficiency these patients together. Most reports
phosphokinase, protein-bound iodine, and of growth hormone to account for his of Hallermann-Streiff syndrome are
butanol-extractable iodine. The urinalysis
short stature. Data from cardiac found in the ophthalmology liter¬
was normal, and a result of the urine fer¬
ric chloride test was again negative. Uri¬ catheterization suggested decreased ature and are concerned primarily
nary 17-hydroxycorticosteroids, 17-keto- thoracic compliance. This may have with the eye abnormalities. Since a

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 Table 1.—Major Clinical Findings Associated With Hallermann-Streiff Syndrome1'29
Age Bird Hypoplastic Proportionate Congenital Microph- Hypotrich- Dental Cutaneous
(yr) Mandible Nanism Cataracts thalmia Anomalies Atrophy
Aubry, 1893 16 +
Bergmeister, 1911 12 +
Schondel, 1943 12
Schondel, 1943 and
Gregersen, 1956
Moehlig, 1946
Hallermann, 1948
Hallermann, 1948 55
8. Marchesani, 1949
9. Marchesani, 1949 +
ÏÔT Streift, 1950 31
ÎÎ7 Körting, 1950 15 +
Ï27 Pau, 1950 26
157 Pau, 1950
Ï4T Ullrich, 1953
Ï57 Weyers, 1954
167 Nizetic, 1954 +
77 Becker, 1954 NB +
ß Gregory, 1955
§7 Gregory, 1955 10
2ÖT Leffertstra, 1956 31 +
27 Gregersen, 1956 25 +
227 Biodi, 1957 +
237 Biodi, 1957
247 Francois, 1958 13
257 Ponte, 1958 18 mo +
267 Ponte, 1958 15 +
277 Ponte, 1958 17
287 Balen, 1959 14
297 Balen, 1959
3Ö7 Balen, 1959
37 Balen, 1959
327 Falls, 1960 30
337 Falls, 1960 5 mo +
347 Falls, 1960 5 wk +
357 Falls, 1960 5 mo +
367 Falls, 1960
377 Bonamour, 1960
387 Calmettes, 1960 16
397 Francois, 1961
4Ö7 Carones, 1961 +
47 Larmande, 1961
427 Larmande, 1961 + +
437 Ponte, 1962 +
447 Guyard, 1962
457 Guyard, 1962 44
467 Manzitti, 1963
477 Manzitti, 1963
487 Hoefnagel, 1965 +
497 Hoefnagel, 1965 5 mo

5Ö7 Hoefnagel, 1965 3 mo

constellation of anomalies is present trician. He should be most aware of counseling.

and numerous organ systems are in¬ all of its clinical manifestations so The mechanism of inheritance in
volved usually from the outset, that he may establish a definitive the Hallermann-Streiff syndrome is
patients with this syndrome may diagnosis, anticipate complications, not clear. Most reported cases thus
frequently be seen first by the pedia- and render prognosis and genetic far are sporadic with family histories

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 Table 2.—Reported Visual Acuity Guyard et al·'7 and the followed
case 3 in 50. Case 31 was the monozy-
case
Following Removal of Cataracts in up by Larmande and described by gotic twin of case 30 and died at age
Patients With Hallermann-Streiff Francois1 demonstrated a familial in¬ 3 months. The cause of death is not
Syndrome
cidence. Two sets of male monozy- recorded.
Visual Acuity gotic twins have been reported. In Most of the literature on this syn¬
Left Right one set5 only one of the twins was drome is concerned primarily with
Case*
4 Schondel5
Eye Eye
20/400
affected, while in the other set-1 both ocular defects. Eye anomalies include
20/400 infants were involved. There is no micro-
6 Hallermann* 20/140 0 congenital cataracts,
7 Hallermann*
10 Streift»
4/400
0
20/400
0
apparent sex predilection. ophthalmia, nystagmus, strabismus,
16 Nizetic" 20/40 Only two of these individuals have chorioretinal atrophy, and peri-
20/200
18 Gregory" 20/120 reproduced. One woman (case 43) papillary choroid atrophy. Even with
19 Gregory» 20/200 4/400
20 Leffertstra"
—

gave birth to two normal children, surgical removal of the cataracts,

1/400 20/40
21 Gregersen' 16/400 20/360 and an affected man (case 45) who functional results are disappointing.
22 Biodi» 0 0 was "distantly related" to his wife Visual acuity measurements from
24 Francois» 20/400 10/400
28 Balen2' 20/20 20/30 fathered a daughter with positive the literature are summarized in
29 Balen21 7/400 20/200 features (case 44). These are, of Table 2.
38 Calmettes et al24 20/400 20/400
40 Carones2' 20/200 20/60 course, too few to establish an in¬ In reports which describe nanism,
43 Ponte» 20/40 2/400 heritance pattern. Most of the other the height and weight of children
44 Guyard et al2' 20/50 0
45 Guyard et al27 0 0 individuals were not married so re¬ usually fall well below 2 standard de¬
productive capacities are unknown. viations. Although few adult mea¬
*Numbers at left correspond to numbers Life expectancy cannot be deter¬ surements are available, the average
in Table 1.
mined from the literature, but death height of girls appears to be approxi¬
showing similarly affected in¬
no from pulmonary infection was re¬ mately 152.4 cm (5 ft) with boys 2.5
dividuals. Only the case reported by ported at age 8 in case 49 and at age to 5.1 cm taller.

References

1. Francois J: Syndromes with congenital cataract (XVI Gregory IDR: Congenital

16. ectodermal dysplasia. Brit
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