hallermann–streiff syndrome: a review

American Journal of Medical Genetics 41:488-499 (1991)

Hallermann-Streiff Syndrome: A Review

M. Michael Cohen, Jr. Departments of Oral Biology and Pediatrics, Faculties of Dentistry and Medicine, Dalhousie University, Halifasc, NS, Canada

The Hallermann-Streiff syndrome is characterized by dyscephaly, hypotrichosis, microphthalmia, cataracts, beaked nose, micrognathia, and proportionate short stature. Cause is unknown; sporadic occurrenee is the rule. Data presented in this review include the characteristics of pregnancy, growth and development, principal manifestations, radiographic and ophthalmological characteristics, and the results of cephalometric study. Potential complications in the syndrome are related to the narrow upper airway associated with the craniofacial configuration. Se- vere complications may include early pulmonary infection, respiratory embarrassment, obstructive sleep apnea, and anesthetic risk. Topics for future study are suggested.

KEY WORDS: Hallermann-Streiff syndrome

INTRODUCTION The Hallermann-Streiff syndrome probably was first

described by Aubry in 1893, although he did not report the complete syndrome. Hallermann in 1948, and especially Streiff in 1950, separated the syndrome from progeria and mandibulofacial dysostosis. An important early paper is that of Frangois who, in 1958, presented 2 personally studied cases, reviewed 22 cases from the literature, and further delineated the syndrome. He fixed the diagnostic criteria of dyscephaly, congenital cataracts (which sometimes resorb spontaneously), microphthalmia, dental anomalies, hypotrichosis, cutaneous atrophy, and proportionate short stature (Table I). The condition has also been called Frangois syndrome [Barrucand et al., 1978; Berbich et al., 19771, Frangois dyscephalic syndrome [Carones, 1961; Frangois, 19821, and oculomandibulodyscephaly [Slootweg and Huber, 19841. Over 150 cases have been recorded to date. Sev- eral extensive reviews [Barrucand et al., 1978; Carles- Mennet, 1979; Frangois, 19821 and surveys [Steel and Bass, 1970; Suzuki, 19701 are available.

Received for publication August 23,1990; revision received Jan-

Address reprint requests to M. Michael Cohen, Jr., D.M.D., uary 25, 1991.

Ph.D., Dalhousie University, Halifax, NS, Canada, B3H 355.

0 1991 Wiley-Liss, Inc.

The syndrome is illustrated in Figures 1-7. Data are presented in several tables: principal characteristics (Table I), pregnancy and growth (Table 11), ophthalmological findings (Table 1111, cephalometric characteristics (Table IV), roentgenographic changes (Table V), and other abnormalities (Table VI).

NOSOLOGIC CONSIDERATIONS The Hallermann-Streiff syndrome can be distin-

guished from the pseudoprogerialHallermann-Streiff (PHS) syndrome, progeria, Wiedemann-Rautenstrauch syndrome, Seckel syndrome, mandibulofacial dysostosis, and mandibuloacral dysplasia. The PHS syndrome [Hall et al., 19741 has similarities to the Haller- mann-Streiff syndrome but has, in addition, severe spastic quadriplegia. Furthermore, appearance at birth is normal except for absence of eyebrows and eyelashes. The disorder is progressive, with limb spasticity and psychomotor delay evident by age 4 months. Progeria differs from the Hallermann-Streiff syndrome because of premature arteriosclerosis, nail dystrophy, acro- micria, and chronic deforming arthritis; the eyes are normal. Wiedemann-Rautenstrauch syndrome is a pro- geroid disorder characterized by growth deficiency, mental retardation, sparse scalp hair, frontal and bi- parietal bossing, diminutive face, beaked nose, small mouth, natal teeth, diminished subcutaneous fat, and large hands and feet. Seckel syndrome is characterized by severe growth deficiency, mental retardation, micro- cephaly, receding forehead, curved nose, micrognathia, and clinodactyly. It is easily distinguished from the Hal- lermann-Streiff syndrome on the basis of prominent eyes without cataracts, malformed ears, and normal temporomandibular joints. Hypotrichosis and cutaneous atrophy also are not components of the Seckel syndrome. Mandibulofacial dysostosis shares in common with the Hallermann-Streiff syndrome micrognathia, high palatal vault, and malar hypoplasia, but usually has lower eyelid colobomas and associated ear anomalies. Mandibuloacral dysplasia is characterized by delayed closure of cranial sutures, mandibular hypoplasia, dysplastic clavicles, and abbreviated terminal pha- langes with acroosteolysis [Gorlin et al., 19901.

Virtually all cases of the Hallermann-Streiff syndrome are sporadic. There is no sex predilection. The syndrome has been described as concordant [Van Balen, 19611 and discordant [Schondel, 19431 in monozygotic twins, and an affected female has had 2 normal children

Hallermann-Streiff Syndrome 489

generations. However, neither of these papers describes Hallermann-Streiff syndrome. FranCois [19821 cited several familial cases as personal communications that have never been published. He further cited 2 affected sibs reported by Hall et al. [19741 as examples, although Hall et al. specifically recognized the condition of their patients as different from Hallermann-Streiff syndrome-the PHS syndrome. Ravindran and Stoops [19791 described an affected mother and infant in 3 sentences with essentially no documentation of findings.

The affected cousins reported by Schanzlin et al. [19801 do not represent a familial example either. Al- though a second cousin clearly had Hallermann-Streiff syndrome, the proband had dup(l0q) with buphthalmos, sclerocornea, total aniridia, nasal abnormality, micrognathia, and bifid halluces. Chromosome studies have been normal in almost all instances [Barrucand et al.,

TABLE I. Principal Manifestations* (n=150)

Abnormalitv %

Dyscephaly 98-99 Cataract 81-90 Microphthalmia 78-83 Dental abnormalities 80-85 Hypotrichosis 80-82 Skin atrophy 68-70 Proportionate short stature 45-68 *After Barrucand et al. [19781 and Carles-Meriment [19791.

[Ponte, 19621. I cannot accept any of the familial cases recorded to date. For example, Guyard et al. 119621 described a father and daughter and Koliopoulos and Pal- imeris [19751 reported what they called “atypical Hal- lermann-Streiff-F’ranCois syndrome” in 3 successive

Fig. 1. Facial characteristics of the Hallermann-Streiff syndrome. Age 6 weeks. (A) Frontal view. (B) Profile view. (C) Eyes, nose.

490 Cohen

Fig. 2. Same patient as shown in Figure 1. Age 1 year. Courtesy of Fig. 3. Same patient as shown in Figures 1 and 2. Age 3 1/z years. R. J. Gorlin, Minneapolis. Courtesy of R. J. Gorlin, Minneapolis.

1978; Berbich et al., 1977; Falls and Schull, 1960; Golomb and Porter, 1975; Hoefnagel and Benischke, 1965; Imamura et al., 1980; Judge and Chakanovskis, 1971; Lamy et al., 19651, with few exceptions. Carones [19611 reported some discrepancy in the size of 2 mem- bers of a pair of D group chromosomes. Jalbert et al. [19681 noted del(Bp).

The sporadic cases reported by Scoppetta et al. 119791 and Steel et al. [1975] are not examples of the syndrome. Consanguinity was reported by Berbich et al. t19771, but in a sibship of 8 children, only one was affected. F’ranqois [19821 cited a number of other instances of consanguinity. However, families that can be verified had only one affected individual per family.

Thus, review of the literature indicates 2 classes of patients labeled Hallermann-Streiff syndrome: typical and atypical. Most cases are typical; a few are atypical. The typical Hallermann-Streiff face is very characteristic, despite variability in expression that may be present. The atypical cases are suspect and account for the well-documented familial instances and a few of the sporadic cases. They illustrate the problem of confusing genuine cases with patients whose tabulated plus and minus findings seem similar. The true Hallermann- Streiff face is so striking that an Augenblick diagnosis can be made. However, even though all classical cases to date have been sporadic and the distinction between Hallermann-Streiff and non-Hallermann-Streiff cases

Fig. 4. Same patient as shown in Figures 1,2, and 3. Age 18. (A) Rontal view. (B) Profile view. Courtesy of R. J. Gorlin, Minneapolis.


Fig. 5 . Hallermann-Streiff syndrome. Hypotrichosis, small palpebral fissures, beaked nose, severe micrognathia. (A) Frontal view. (B) Profile view. (C) Cephalometric tracing showing marked mandibular deficiency, antegonial notching, steep mandibular plane, prominent labial profile, obtuse nasolabial angle, and lack of chin contour. (D) Panorex radiograph showing missing teeth. A-C from M. M. Cohen, Jr., Malformation Syndromes, in “Surgical Correction of Dentofacial Deformities,” W. H. Bell, W. R. Profiit, and R. P. White, Jr., Eds., Saunders, Philadelphia, 1980, Ch. 2, pp. 7-44.

is clear cut, possible familial instances and/or borderline cases-if they exist a t all-need to be documented carefully in the future.

GROWTH AND DEVELOPMENT Birth weight is normal in about 64%, prematurity

and/or low birth weight occurring in the other 36% [Su- zuki et al., 19701. Short stature is seen in 45-68% [Fran- Gois, 19821. Growth is diminished proportionately (Fig. 8), being at least 2-5 SD below the mean. Final height attainment for females is about 152.4 cm, with males being 2.5-5.0 cm taller [Steele and Bass, 19701 (Ta- ble 11).

Hypogenitalism has been reported in 10-12% [Barru- cand et al., 1978; Carles-Mermet, 1979; Hoefnagel and Benirschke, 1965; Srivastava et al., 19661. Also documented have been cryptorchidism, hypospadias, clitoral

enlargement, breast asymmetry, and breast atrophy [Barrucand et al., 1978; FranGois, 19821. Axillary and pubic hair may be scant [Falls and Schull, 1960; Fran- Gois, 19581.

PERFORMANCE Mental deficiency has been noted in about 15%’

(n=58) [Suzuki et al., 19701, although an estimate of 31% has been given elsewhere [FranGois, 19821. Judge and Chakanovskis [19711, in reviewing 34 cases, indicated that 4 patients were severely retarded and 14 others were “retarded, slightly retarded,. . . (had) . . . psychomotor retardation . . . (or) . . . slow development.” Crevits et al. [19771 have warned that the psy- chometric aspects of the syndrome have been treated very subjectively, with only rare instances of psycho- metric testing. Hyperactivity, choreoathetosis, and gen-

492 Cohen

Fig. 6 . Closeup of cephalometric radiograph showing anterior placement of temporomandibular joint (arrow).

eralized tonic-clonic seizures have been noted occa- sionally [Crevits et al., 1977; Falls and Schull, 1960; Judge and Chakanovskis, 19711.

CRANIOFACIAL CHARACTERISTICS The face is small with a thin, tapering, “pinched”

nose, and receding chin [Sclaroff and Eppley, 19871. An odd-shaped, bulging skull with brachycephaly is often accompanied by frontal or parietal bossing. Mild micro- cephaly and malar bone hypoplasia also occur but are

not constant [Franqois, 1982; Lamy et al., 19651. Gaping )r dehiscence of sutures, as well as delayed closure of Fontanelles, have been described by nearly all authors. The nose is thin, pointed, and often curved and may have 3 tendency to septa1 deviation [Blodi, 1957; Ponte, 19621. Hypotrichosis, especially of the scalp, brows, and lashes, xcurs in about 8 0 4 2 % [Barrucand et al., 1978; Carles- Mermet, 1979; Golomb and Porter, 1975; Gratton et al., 1989; Suzuki et al., 19701. Scanning electron microscopy has shown absent or abnormal cuticle development in the hair shafts [Golomb and Porter, 19751. Alopecia is most prominent about the frontal and occipital areas, but is especially marked along suture lines [Sugar et al., 19711. Cutaneous atrophy, present in about 68-70% [Bar- rucand et al., 1978; Carles-Mermet, 19791, is largely lim- ited to the scalp and nose. Scalp skin is thin and taut, and scalp veins are prominent. Similar changes, often focal, are observed on the nose (Figs. 1-51,

Ocular findings are summarized in Table 111. Previ- ously undiagnosed patients tend to visit ophthalmolo- gists because of visual impairment from congenital cataract. Microphthalmia of variable severity (7843%) and bilateral congenital cataracts (81-90%) occur with high frequency [Barrucand et al., 1978; Carles-Mermet, 1979; Suzuki et al., 19701. Cataracts consist of milky white liquefied lens masses that often resorb spontaneously [F’ranqois, 1982; Wolter and Jones, 19651. Blue sclerae have been described in about 22-31%, nystagmus in 32-45%, strabismus in 33-37%, glaucoma in 7- 11%, pupillary membrane persistence in 5%, and down- slantingpalpebral fissures in 12-13% [Barrucand et al., 1978; Carles-Mermet, 1979; Hopkins and Horan, 1970; Lamy et al., 1965; Sugar et al., 1971; Suzuki et al., 1970; Teuscher, 1974; Van Balen, 19611. Donders [19771 pub-

Fig. 7. (A, B) Lateral and frontal cephalometric comparison of woman with Hallermann-Streiff syndrome (age 33 years) and normal white woman of similar age. Solid line and shaded area: Hallermann- Streiff syndrome. Dotted line indicates normal case for comparison. Note reduced size of cranium and portion of calvaria with step in region above lambdoid suture. Deficient calvarial ossification particularly adjacent to lambdoid suture. Thin parietal bones. Platybasia of cranial base. Reduced interorbital distance, small orbits, and hypoplastic malar bones. Short mandible, obtuse gonial angle and anteriorly placed temporomandibularjoints (by 2.7 cm). From H. F’riede et al., J. Craniofacial. Genet. Dev. Biol. Suppl. 1:189, 1985.


100

80

2 60

5

rl

u - 40

20

0 I 2 3 4 5 Age (years)

I I

0 1 2 3 4 5 Aee (years)

Fig. 8. Length (A) and weight (B) of 2 Japanese girls (Case 1, open circles; Case 2, closed circles) with Hallermann-Streiff syndrome. Dotted line indicates average length (A) and weight (B) ofnormal Japanese girls. Case 1: Birth length, 45 cm (average 49.6 cm); birth weight, 2,720 g (average 3,000 9); head circumference at birth, 33 cm (average 35 cm). Case 2: Birth weight, 2,200 g; a t 7 months, length was 58 cm (average 65.5 cm), weight was 4.8 kg (average 7.35 kg), and head circumference was 41.5 cm (average 42.2 cm). From Suzuki et al., Dev. Med. Child Neurol., 12:496-506, 1970.

lished a histopathologic study of the eye from an autopsy case. Anomalies of the fundus, conjunctiva, and cornea as well as miscellaneous ocular findings are well documented in several accounts [Barrucand et al., 1978; Blodi, 1957; Carles-Mermet, 1979; Falls and Schull, 1960; Francois, 1982; Francois, 1958; Gregersen, 1956; Hallermann, 1948; Lamy et al., 1965; Ludwig and Kort- ing, 1950; Moehlig, 1946; Sugar et al., 1971; Ullrich and Fremerey-Dohna, 1953; Van Balen, 1961; Walbaum et al., 1968; Wolter and Jones, 19651.

The mandible is hypoplastic with double chin and central clefting or dimpling [Blodi, 1957; Caspersen and Warburg, 1968; Francois, 1958; Gregersen, 1956; Haller- mann, 1948; Streiff, 19501. The ascending ramus is usually short, and the condyle may be missing or the fossa hypoplastic [FranGois, 1958; Judge and Chakanovskis, 1971; Kurlander et al., 19661. Roentgenographic exam- ination shows a characteristic temporomandibular joint displacement of approximately 2 cm forward from its normal position (Fig. 6) that is located just in front of the

external auditory meatus [Van Balen, 19611. The palate is high and narrow and the paranasal sinuses are diminished in size [Falls and Schull, 19601. Microstomia is present in about 10% [Judge and Chakanovskis, 1971; Van Balen, 19611. Cephalometric (Table IV) (Fig. 7) and anthropometric studies have been carried out [Friede et al., 1985; Haberman and Clement, 19791. Fbentgeno- graphic changes are summarized in Table V.

Dental anomalies are common (8045%) and may include absence of teeth, persistence of deciduous teeth (Fig. 5D), malocclusion and open bite, malformed teeth, severe and premature caries, supernumerary teeth, and natal teeth [Aubry, 1893; Barrucand et al., 1978; Blodi, 1957; Carles-Mermet, 1979; Caspersen and Warburg, 1968; Falls and Schull, 1960; FranCois, 1982; Francois, 1958; Hallermann, 1948; Honda et al., 1990; Hoefnagel and Benirschke, 1965; Hutchinson, 1971; Ludwig and Korting, 1950; Moehlig, 1946; Patterson et al., 1982; Schondel, 1943; Srivastava et al., 1966; Steele and Bass, 1970; Streiff, 19501.

494 Cohen

TABLE IV. Cephalometric Characteristics* (n = 7) TABLE 11. Pregnancy and Growth*

n %

Pregnancy (n = 28) Uneventful 19 Vaginal bleeding (1-4 mo) 4 Other abnormalities 5

Term, normal 0 2 , 5 0 0 g) 18 Term, low (<2,500 g) 2 Premature, low 8

Proportionate short stature Mean final height attainment

Birthweight (n = 28)

Growth

Females (cm) Males (cm)

(68) (14) (18)

(64)

(29) (7) (36)

(45-68)

152.4 154.9-157.4

*After F'ranqois [1982], Steele and Bass [19701 and Suzuki et al. [19701.

A well-documented histopathologic study of den- toalveolar abnormalities observed at autopsy is available. Slootweg and Huber [1984] found a root dentin abnormality consisting of irregular dentin and osteo- dentin. Also observed were premature disintegration of the dental lamina and Hertwig's epithelial root sheath. All permanent molars failed to form except first molars. Agenesis of teeth is explained by early disintegration of the dental lamina, and lack of permanent teeth explains persistence of the deciduous teeth.

(YI'HER FINDINGS Dinwiddie et al. [ 19781 recorded various heart anoma-

lies including pulmonic stenosis, ASD, VSD, PDA, and tetralogy of Fallot. They indicated a frequency of about 4.8%.

Chandra et al. [1978] reported a patient with deficiency of humoral immunity and hypoparathyroidism. Although immunodeficiency, hypoparathyroidism, and

TABLE 111. Ocular Findings* ( ~ 1 5 0 ) Abnormality %

Congenital cataract 81-90

Strabismus 33-37

Microphthalmia . 78-83 Nystagmus 32-45

Blue sclerae 22-31

h n d u s anomalies 18-22

Corneal abnormalities 9-14 Downslanting palpebral fissures 12-13 Intraocular hypertension 7-11 Iris atrophy 10-14

Sparse eyelashes and eyebrows 29

Conjunctival defects 11

Vitreous degeneration 8 Eyelid anomalies 6 Iris coloboma 5 Pupillary membrane persistence 5

Disc coloboma 1

Enophthalmos 2.5-4 Epicanthic folds 2-4

Choroidal coloboma Ptosis of the eyelids HvDodasia of the lacrimal puncta

1 1-3 2

E6;bb;lbar tumor 1

Calvaria" Brachycephaly Thin calvaria Delayed closure of fontanelles Wide sutural areas

Cranial base Platybasia Depressed sella Elevated anterior cranial fossa

Midface/orbits Malar hypoplasia Beaked nose Hypotelorism Small orbits

Adequate horizontal dimension Adequate vertical dimension

Small ramus Small body Obtuse gonial angle Temporomandibular joint anteriorly placed

Retained primary teeth Missing permanent teeth Malocclusion (Class 11, Division 1) Open bite

Reduced in some cases

Maxilla

Mandible

Dental

Airway

*Adapted from Friede et al. [19851. " I have adapted the calvaria section from what is known from the general Hallermann-Streiff literature; 6 of the 7 patients that Friede et al. [19851 analyzed were not infants (ages 33,18,17,22,12, and 59 years, respectively).

TABLE V. Roentgenographic Changes*

Distinctive Hypoplastic mandibular ramus Condyles may be absent Temporomandibular joint displaced anteriorly

Brachycephaly Delayed closure of fontanelles Wide sutures Frontal or parietal bossing Thin calvarial bones Wormian bones Platybasia Depressed sella turica Small orbits Hypoplastic malar bones Micrognathia Obtuse gonial angle Missing permanent teeth Retained deciduous teeth Thin gracile tubular bones

Calcification of falx cerebelli Scaphocephaly Cervical vertebral anomalies Elevated scapulae Lordosis Scoliosis Spina bifida Osteoporosis Platyspondyly Syndactyly

Other

Occasional

*Adapted primarily from Kurlander et al. [19661 and Friede et al. *After Barrucand et al. [19781 and Carles-Mermet 119791. [19851.


cardiac anomalies have now been observed in the Hal- lermann-Streiff syndrome, true DiGeorge sequence has not occurred. The patient reported by Chandra et al. [19781 had normal cell-mediated immunity with reduced serum IgG and plasma opsonic function.

A great many other abnormalities have been observed (Tables V and VI) including occipital bossing, hydro- cephaly, calcification of the falx cerebri [Barrucand et al., 1978; FranGois, 1982; Larmande et al., 1962; Zolog, 19671, osteoporosis [Moehlig, 19461, syndactyly [Van Balen, 19611, lordosis and/or scoliosis [Ludwig and Kort- ing, 1950; Schondel, 19431, spina bifida, winging of the scapulae [Judge and Chakanovskis, 1971; Ponte, 1962; Suzuki et al., 1970; Van Balen, 19611, pectus carinatum, and pectus excavatum [Franqois, 1982; Van Balen, 19611. Vitiligo and livedo have also been noted [Ran- Gois, 1958; Lamy et al., 1965; Zolog, 19671.

COMPLICATIONS Potential complications in the Hallermann-Streiff syn-

drome are related to the narrow upper airway associated with the craniofacial configuration. Severe complications may include early pulmonary infection, respiratory embarrassment, obstructive sleep apnea, and anesthetic risk. To date, reports of such complications have been anecdotal. Their frequency is unknown, but I suspect that some form of respiratory embarrassment may be more common than generally supposed.

Severe Early Pulmonary Infection The most severe complication is early pulmonary in-

fection resulting in the patient's death. Hoefnagel and Benirschke [ 19651 reported death from pulmonary infection in one case at age 3 years and at age 8 years in another. One of 3 cases reported by Dinwiddie et al. [19781 died with fulminating bronchopneumonia at age 3 1/2 years. The patient had undergone pulmonary val- votomy and pericardial window formation using cardio- pulmonary bypass a t age 2 years. Van Balen [19611 reported an early demise at age 3 months but did not specify the cause. I regard early assessment for possible airway dysfunction, immunodeficiency, or cardiovascular anomalies as mandatory.

TABLE VI. Other Abnormalities* ( n ~ 1 5 0 ) Abnormality" %

Mental deficiencyb 15 Neurologic manifestations" Infrequent Skeletal defects" 10-50 Genital anomalies 10-12 Cardiac defects 2-9 Ear anomalies" 9 Hematopoietic abnormalities 7 Pulmonary anomalies 3 Digestive system abnormalities" 3 Muscular hypotrophy 3 Hepatic anomalies 2 Renal anomalies 1-2 *After Barrucand et al. [19781 and Carles-Meriment et al. [19791. a Categories of percentages are not clearly defined in the literature. Based on Suzuki et al. [19701.

'Based on Crevits et al. [19771.

Respiratory Embarrassment A narrow upper airway may lead to respiratory em-

barrassment. Tracheostomies were necessary in the patients reported by Van Balen [19611 and Falls and Schull [19601. Obstructive sleep apnea (OSA) has been observed in some instances. The patient of Ryan et al. [19901--an 8-year-old girl-had a history of severe snoring since birth, nocturnal apneic episodes, excessive daytime somnolence, and behavior problems. Marked micrognathia, microstomia, and narrowing of the posterior oropharynx were described. Overnight polysomno- gram showed OSA, arterial oxygen desaturation, cardiac arrhythmias, and sleep fragmentation. Of 7 Hallermann-Streiff patients studied by F'riede et al. [19861,2 had OSA. One was a 48-year-old woman with hypoxia, hypercarbia, pulmonary hypertension, tri- cuspid insufficiency, and right ventricular failure.

In recent years, much has been learned about OSA in children. Signs and symptoms, workup, diagnosis, and complications have been discussed by Brouillette et al. [1982; 19841 and Guilleminault et al. [1981]. The severity of OSA in children with craniofacial anomalies ranges from mild to life-threatening. Failure to thrive or growth deficiency, systematic hypertension, cardiorespiratory failure, and neurological damage are common [Guilleminault et al., 1981; Brouillette et al., 1982; Lauritzen et al., 1986; Bate et al., 1984; Everett et al., 19871. Many different treatments are available and de- pend on the type and level of obstruction, its cause and severity, age of the patient, DQIIQ, ability to comply, and personal preference. Treatment may include tracheostomy, mandibular advancement, mandibular and chin-hyoid advancement, palatal shortening, (uvulo- palatopharyngoplasty, UPPP), tonsillectomy, surgical reduction of the tongue, mandibular positioning dental appliance, and tongue retaining device. Nonsurgical treatment may include continuous positive airway pressure (CPAP) therapy, weight loss, medication, head and neck extension collars, and sleep position modification [Clark and Nakano, 1989; Brouillette et al., 1984; Guilleminault et al., 1981; 1986; Riley et al., 1987; 1989; Schmidt-Nowara, 19841.

Since, on the average, children with OSA experience a 2-year delay in referral for proper diagnosis, Hallermann- Streiff patients in particular, who are predisposed to upper airway compromise because of their craniofacial configuration, should be monitored especially carefully. Any Hallermann-Streiff patient who exhibits snoring andlor daytime hypersomnolence (no matter how minor in degree) should be referred immediately to a sleep cen- ter for proper diagnosis and treatment to prevent dan- gerous sequelae.

Tracheostomy, although curative, is associated with major long term problems related to depression and dif- ficulties with stoma care. Ryan et al. [19901 reported successful treatment of an OSA Hallermann-Streiff patient using CPAP therapy. Immediate improvement in all symptoms was observed. The patient's weight by stature-earlier at the 15th centile and decreasing to well below the 5th centile with progression of OSA symptoms-increased to greater than the 50th centile 1 year after starting CPAP therapy (Fig. 9).

496 Cohen

I 95 26 -

24 -

22 - - 9 2 0 -

6 1 8 - - -

1 6 -

14 -

12-

85 90 95 100 105 110 115 120 Stature (cm)

Fig. 9. Centile chart for weight by stature in Hallermann-Streiff patient from ages 8 to 9 years. History of severe obstructive sleep apnea with treatment by nasal continuous positive airway pressure therapy. Arrow indicates beginning of therapy. Change in weightlheight ratio for 1 year period of time increasing from below 5th centile to above 50th centile. From C. F. Ryan et al., Clin. Pediatr. 29:122, 1990.

Surgical procedures have been used for some patients with OSA. Riley et al. 119891 reported good responses by polysomnography before and 6 months following mandibular and chin-hyoid advancement (n = 55 adults). Man- dibular advancement in a 15-year-old Hallermann- Streiff patient (Fig. 10) is illustrated in the report by Patterson et al. [19821, although their patient did not have OSA. Surgery was carried out for cosmetic purposes and to establish maxillomandibular harmony. Sclaroff and Eppley [1987] performed a LeFort I osteotomy, a mandibular osteotomy, and an advancement genioplasty with a suprahyoid myotomy on a Haller- mann-Streiff patient who had no history of respiratory embarrassment.

Fig. 10. Cephalometric tracing of 15-year-old Hallermann-Streiff patient with mandibular advancement surgery. Solid line indicates presurgical position. Dotted line indicates postsurgical position 5 years following surgery. From G. T. Patterson et al., J. Oral Maxillofac. Surg. 40:380, 1982.

Anesthetic Risks Because of possible surgery, such as the repair of a

cardiovascular defect, ophthalmological procedure, or mandibular advancement, it is essential to understand the particular anesthetic risks to Hallermann-Streiff syndrome patients. Such risks have been discussed by Ravindran and Stoops [1979] and Sataloff and Roberts [ 19841.

Because of micrognathia, microstomia, and serious upper airway compromise in the syndrome, laryngoscopy and endotracheal intubation may be difficult. When natal teeth are present, they may be brittle and easily broken or avulsed during laryngoscopy. Oro- tracheal intubation may be precluded by anterior placement or absence of the temporomandibular joints. The hypoplastic nose and deviated nasal septum may make nasotracheal intubation difficult even when using direct vision. Blind nasal intubation may also be difficult because of highly arched palate, anterior glottis, and posterior displacement of the trachea. Open bite may prevent closure of the mouth to facilitate blind nasotracheal intubation. Specific preparation should be made for both nasal and oral intubation in patients with the Hallermann-Streiff syndrome. Several sizes of endotracheal tubes, stylets, laryngoscope blades, and intu- bating forceps should be available. Fiberoptic endoscopy should be considered. A variety of oropharyngeal and nasopharyngeal airways should be available in case upper airway obstruction occurs. Rapid intravenous induc- tion should only be carried out if direct laryngoscopy demonstrates the glottis easily. Patients should not be extubated until they are fully awake and have recovered from neuromuscular blockade.

Presurgical tracheotomy should be considered in Hallermann-Streiff syndrome patients. If not done, an otolaryngologist should be available for emergency tracheotomy following extubation, should one be required. Management of the airway in the 2 patients reported by Sataloff and Roberts [19841 is instructive. One patient was a teenage girl (age unspecified) who underwent cosmetic surgery with general anesthesia. Because intubation was extremely difficult, tracheotomy was performed to establish a safe airway access. Post- operatively, the patient’s breathing and sleeping im- proved so significantly that she decided to keep the tracheotomy tube; she plugged it by day and breathed through it at night. The other case involved a 46-year- old man who underwent an ophthalmologic procedure with general anesthesia. He had microstomia, micrognathia, a large tongue, and a maximum opening of 1.5 cm between the maxillary and the mandibular inci- sors. With maximum neck extension, the cricoid car- tilage was still partially below the level of the sternum. Because of traumatic intubation, the anesthesiologist requested an otolaryngologist to be available for emergency tracheotomy, if necessary, following extubation; it was thought that reintubation would not be possible if the airway became obstructed. In this particular case, a tracheotomy was, in fact, performed prior to extubation. Postoperative discussion with the patient revealed that he had been unable to sleep comfortably and frequently slept sitting-up. He was also unable to eat certain kinds


tested; about 10 Hallermann-Streiff cases together with their parents would be informative in this con- nection.

Particularly important in future studies will be the documentation of Hallermann-Streiff individuals who have reproduced. Also, high resolution banding studies should be carried out. The only chromosome alterations observed to date have been from the prebanding era.

The study of growth patterns would provide standard curves for height, weight, and head circumference in the Hallermann-Streiff syndrome. Since growth deficiency of prenatal onset and proportionate short stature are present in many Hallermann-Streiff syndrome cases, cell culture from affected individuals should be studied to see if their cells manifest the growth defect. Pious et al. [19751, in a preliminary study of in vitro fibroblast doubling time in primary growth deficiency disorders, found slower than normal cell cycles in trisomy 18 syndrome, trisomy 13 syndrome, Rothmund-Thomson syndrome, and Seckel syndrome.

The cause( s) and frequency of early life-threatening pulmonary infection are not clear. The problem needs further study and documentation. At least 4 factors can be identified that individually or in combination may be contributory. First, the narrow air passages in the Hallermann-Streiff syndrome may result in feeding diffi- culties, perhaps abnormal glottic closure, and mild aspira- tion of nourishment. Second, growth deficiency of prenatal onset with continuation postnatally-a manifestation in about 36% of Hallermann-Streiff cases-may predispose toward pulmonary infection. Third, immunodeficiency has been documented in one instance by Chandra et al. [1978], but immune status has not been assessed in other reported cases. It should be studied in all future cases. In growth deficiency of prenatal onset in general, immunocompetence may be comprised. Chandra [19751 studied 26 patients with intrauterine growth deficiency and found significantly reduced peripheral T lympho- cytes, impaired cell-mediated immunity, reduced opsonic function of plasma, and severe impairment in bac- tericidal capacity and in the oxidative metabolism of polymorphonuclear leukocytes. Fourth, cardiovascular anomalies, reported in a few instances, may predispose toward pulmonary infection.

The cause of the growth deficiency in OSA is unclear, but may be due to reversible hypothalmic-pituitary dysfunction. Grunstein et al. [1989] studied the effects of OSA on neuroendocrine function in a cross-sectional study of 225 men and a longitudinal study of 43 men before and after successful CPAP therapy. Results indicated selective defects in GH-IGF-I and gonadal axes. The common manifestations of dominant hypothalamic regulation in these axes together with absence of increased plasma gonadotropin levels suggest that the principal defect is in hypothalamic regulation of pituitary hormone secretion. Reduced plasma IGF-I and tes- tosterone levels were related to the severity of OSA and were reversed by CPAP therapy. Reversibility strongly suggests that neuroendocrine dysfunction is a conse- quence of OSA rather than an independent primary disorder of the hypothalanus or higher neural levels. Since the severity of the hypoxemia is correlated with

of foods (such as salads) and breathe at the same time. He chose to keep the tracheotomy permanently. During the ensuing 6 years, he reported that sleeping and eat- ing were much less difficult.

COMMENTS AND FUTURE STUDIES Over 150 cases of the Hallermann-Streiff syndrome

have been reported to date. As expected, most articles have appeared in the ophthalmology journals so that eye manifestations have had extensive coverage. It should also be noted that the rarity of the Hallermann-Streiff syndrome is presumed because no estimates of the birth prevalence are known. Although a number of review articles have been cited, further studies of the Haller- mann-Streiff syndrome should be carried out and pooled for analysis. Topics in need of study are listed in Table VII. I am willing to act as a central repository and clearing house for all incoming Hallermann-Streiff data. Any available data are welcome. The following comments are pertinent.

Cause is unknown. To date all cases of classic Haller- mann-Streiff syndrome have been sporadic. Given over 150 reported cases, it appears extremely unlikely that traditional autosomal dominant or autosomal recessive inheritance can be invoked. Uniparental disomy with both alleles derived from the same parent is a possi- bility. Using one informed DNA marker per chromosome, the uniparental disomy hypothesis could be

TABLE VII. Studies of Hallermann-Streiff Syndrome Patients for Pooled Analysis

Cause Pedigree Paternal and maternal ages at conception High resolution banding of chromosomes Testing for uniparental disomy

Length of gestation Complications

Birth length, weight, head circumference (OFC) Height, weight, OFC during growth period Cephalometric radiographs Cell cycle studies

Pregnancy

Growth

Performance DQ/IQ Nekdogical abnormalities, if present Psychosocial adaptation

Immunocompetence Various studies

Respirology Oropharyngeal and nasopharyngeal function Respiratory embarrassment Pulmonary infection, if present Obstructive sleep apnea

Polysomnographic studies Neuroendocrine studies Growth studies before and following treatment Documentation of various types of treatment

Experience with general anesthesia

Hallermann-Streiff characteristics Cardiovascular findings Endocrine findings Other unusual findings Radiographic findings

Clinical findings

498 Cohen

n

\ i. mandibulofacial dysostosis, the curvature of the lower border of the mandible was found to be syndrome-specific; a computer-generated polynomial equation characterized the curve in different patients and within the same patient at different ages [Roberts et al., 19751.

ACKNOWLEDGMENTS I wish to thank Bryan Hall for inviting me to address

the topic of the Hallermann-Streiff syndrome at the 11th Annual David W. Smith Workshop in Lexington, Kentucky. I am also grateful to Han Brunner who read the manuscript and made helpful suggestions. Finally, I would like to acknowledge Ruth MacLean for all her help on this project.

REFERENCES Aubry M (1893): Variete singuliere dalopecie congenitale: alopecie

suturale. Ann Dermatol Syphiligr (Paris) 42399-900. Barrucand D, Benradi C, Schmitt J (1978): Syndrome de FranGois. A

propos de deux cas. Rev Oto-Neuro-Ophthal 50:305. Bate TWP, Price DA, Holme CA, McGucken RB (1984): Short stature

caused by obstructive apnea during sleep. Arch Dis Child 59:78-80. Berbich A, Benradi F, Sekkat A (1977): Syndrome de Franqois. Arch Fig. 11. Diagramatic tracing of a cephalometric radiograph which Ophtalmol (paris) 37:723-730. can be used to study the airway and also the relationship between the +

craniofacial configuration, airway, hard and soft palate, tongue, hyoid, and vertebral column. Anatomic points, contours, and planes used to identify airway, tongue, and hyoid variables [UPW, upper pharyngeal wall; MPW, middle pharyngeal wall; LPW, lower pharyngeal wall; E, epiglottis; H, hyoid; TT, tongue tip; (1) linear distance between the most anterior point on the atlas and the tip of the posterior nasal spine; (2) posterior airway space; (3) tongue length; (4) tongue height; (5) vertical position of the hyoid; (6) another, different measure of the vertical position of the hyoid; (7) anteroposterior position of the hyoid]. From Lowe et al., Am. J . Orthod. Dentofac. Orthop., 90:484-491,1986.

neuroendocrine changes, the principal cause appears to be neuroendocrine dysfunction rather than the concomi- tantly occurring sleep fragmentation.

Cephalometric study' would serve several purposes. First, speech pathologists since the mid-1930s and, in more recent years, orthodontists [Lowe et al., 1986al have used cephalograms to study and measure the airway and the relationships between the craniofacial configuration, airway, hard and soft palate, tongue, hyoid, and vertebral column (Fig. 11). Measurements from three-dimensional CT reconstructions [Lowe et al., 1986133 are also possible. Second, cephalometric study provides an important baseline for any contemplated dentofacial reconstruction. Third, the craniofacial growth pattern could be analyzed longitudinally. The facial skeleton and, in particular, the mandible, could be studied for possible syndrome-specific patterns.2 In

Cephalometric study for the purposes indicated here should include (1) the entire cranial outline (not just the cranial base and face used by some orthodontists), (2) clear definition of the soft tissue boundaries of the airway, and (3) clear definition of the soft tissue facial profile as well as the facial skeleton.

The study of the craniofacial growth pattern, including analysis for possible syndrome-specific patterns, should not be taken to mean that I a m recommending cephalograms for the diagnosis of the Hallermann-Streiff syndrome per se. The diagnosis can cer- tainly be established without cephalograms. Simple radiographic study of temporomandibular joint position might be useful for syndrome diagnosis, bu t only in selected (questionable) instances.

Blodi FC (1957): Development anomalies of the skull affecting the eye. Arch Ophthalmol 57593-610.

Brouillette RT, Fernbach SK, Hunt CE (1982): Obstructive sleep apnea in infants and children. J Pediatr 100:31-40.

Brouillette R, Hanson D, David R (1984): A diagnostic approach to suspected obstructive sleep apnea in children. J Pediatr 10510-14.

Carles-Mermet B (1979): Dyscephalie a t6te d'oiseau (signes oculaires et 6tiologie). A propos de 4 observations et revue de la literature. Theeis, Lyon.

Carones AV (1961): Syndrome dysckphalique de Franqois. Ophthal- mologica 142:510-518.

Caspersen I, Warburg M (1968): Hallermann-Streiff syndrome. Acta Ophthalmol (Kbh) 46:385-390.

Chandra RK (1975): Fetal malnutrition and postnatal immunocompetence. Am J Dis Child 129:450-454.

Chandra RK, Joglekar S, Antonio Z (1978): Deficiency of humoral immunity and hypoparathyroidism associated with the Haller- mann-Streiff syndrome. J Pediatr 93:892-893.

Clark GT, Nakano M (1989): Dental appliances for the treatment of obstructive sleep apnea. JADA 118:611-619.

Crevits L, Thiery E, Van der Eechem H (1977): Oculomandibular dyscephaly (Hallermann-Streiff-FranCois syndrome) associated with epilepsy. J Neurol 215:225-230.

Dinwiddie R, Gewitz M, Taylor JFX (1978): Cardiac defects in the Hallermann-Streiff syndrome. J Pediatr 92:77.

Donders PC (1977): Hallermann-Streiff syndrome. Documenta Oph- thalmol 44:161-166.

Everett AD, Koch WC, Saulsbury FT (1987): Failure to thrive due to obstructive sleep apnea. Clin Pediatr 26:90-92.

Falls HF, Schull WJ (1960): Hallermann-Streiff syndrome: A dyscephaly with congenital cataracts and hypotrichosis. Arch Ophthalmol 63:409-420.

Franqois J (1982): Franqois dyscephalic syndrome. Birth Defects 18(6):595-619.

Franqois MJ (1958): A new syndrome: Dyscephalia with bird face and dental anomalies, nanism, hypotrichosis, cutaneous atrophy, microphthalmia and congenital cataract. Arch Ophthalmol 60:842- 862.

Friede H, Lopata M, Fisher E, Rosenthal IM (1985): Cardiorespiratory disease with Hallermann-Streiff syndrome: Analysis of craniofa- cia1 morphology by cephalometric roentgenograms. J Craniofac Genet Dev Biol (Suppl) 1:189-198.

Golomb RS, Porter PS (1975): A distinct hair shaft abnormality in the Hallermann-Streiff syndrome. Cutis 16:122-128.


Gratton CEH (1989): Atrophic alopecia in the Hallermann-Streiff syndrome. Clin Esp Dermatol 14:250-252.

Gregersen E (1956): Ocular abnormalities in progeria. Acta Ophthal- mol (Kbh) 34:347-354.

Grunstein RR, Handelsman DJ, Lawrence SJ, Blackwell C, Caterson ID, Sullivan CE (1989): Neuroendocrine dysfunction in sleep apnea: reversal by continuous positive airway pressure therapy. J Clin Endocrin Metab 68:352-358.

Guilleminault C, Korobkin R, Winkle R (1981): A review of 50 children with obstructive sleep apnea. Lung 159:275-287.

Guilleminault C, Nino-Murcia G, Heldt G, Baldwin R, Hutchinson D (1986): Alternative treatment to tracheostomy in obstructive sleep apnea syndrome: nasal continuous positive airway pressure in young children. Pediatrics 78:797-802.

Guyard M, Perdriel G, Ceruti F (1962): Sur deux cas de syndrome dyscephalique a t&e d’oiseau. Bull Soc Fr Ophtal 62:443-447.

Haberman H, Clement PAP (1979): The value of anthropometrical measurements in a case of Hallermann-Streiff syndrome. Rhinol- ogy 17:179-194.

Hall BD, Berg BD, Rudolph RS, Epstein CJ (1974): Pseudoprogerid Hallermann-Streiff (PHS) syndrome. Birth Defects 10(7):137.

Hallermann W (1948): Vogelgesicht und Cataracta congenita. Klin Monatsbl Augenheilkd 113:315-318.

Hoefnagel D, Benirschke K (1965): Dyscephalia mandibulo- oculofacialis (Hallermann-Streiff syndrome). Arch Dis Childh 4057-61.

Honda E. Inoue T. Domon M. Sasaki T. Uchida T (1990): Dental radiographic signs characteristic to Hallermann-Streiff syndrome. Oral Surg 70:121-125.

Hopkins DJ, Horan EC (1970): Glaucoma in the Hallermann-Streiff syndrome. Br J Ophthalmol54:416-422.

Hutchinson D (1971): Oral manifestations of oculomandibulodyscephaly with hypotrichosis (Hallermann-Streiff syndrome). Oral Surg 31:234-247.

Imamura S, Ikeda E, Yoshida H (1980): Hallermann-Streiff syndrome: Case report. Dermatologica 160:354-357.

Jalbert P, Gilbert Y, Leopold P, Mouriquand C, Beaudoing A (1968): Syndrome d’Hallermann-Streiff-Franqois, a propos d’une nouvelle observation associee B une anomalie caryotypique 4P. Pediatrie 23:703-705.

Judge C, Chakanovskis J E (1971): The Hallermann-Streiff syndrome. J Ment Defic Res 15:115-120.

Koliopoulos J, Palimeris G (1975): Atypical Hallermann-Streiff- Franqois syndrome in three successive generations. J Pediatr Oph- thalmol 12:235-239.

Kurlander GJ, Lavy NW, Campbell JA (1966): Roentgen differentia- tion of the oculodentodigital syndrome and the Hallermann-Streiff syndrome in infancy. Radiology 86:77-85.

Lamy M, Jemmet J , Maroteaux P, Assan N (1965): La dyscephalie (syndrome de Hallermann-Streiff-Franqois). Arch Fr Pediatr 22:929-938.

Larmande A, Gillot F, Balaut J, Cohen JP, Schaeffer J C (1962): Dysce- phalie $I t&e d’oiseau (Syndrome d’Hallermann-Streiff-Franqois). Pbdiatrie 49:313.

Lauritzen C, Lilja J , Jarlstedt J (1986): Airway obstruction and sleep apnea in children with craniofacial anomalies. Plast Reconstr Surg 77:l-5.

Lowe AA, Santamaria JD, Fleetham JA, Price C (1986a): Facial morphology and obstructive sleep apnea. Am J Orthod Dentofac Orthop 90:484-491.

Lowe AA, Gionhaku N, Takeuchi K, Fleetham JA (1986b): Three- dimensional CT reconstructions of tongue and airway in adult sub- jects with obstructive sleep apnea. Am J Orthod Dentofac Orthop 90:364-374.

Ludwig A, Korting G (1950): Vogt-Koyanagi-ahnliches Syndrom und mandibulofaciale Dysostosis (Franceschetti-Zwahlen). Arch Der- matol Syph (Berlin) 190:307-319.

Marchesani 0 (1949): Uber Beziehungen zwischen Wachstum und Nervensegmenten. Dtsch Ophthalmol Gesell 5534-46.

Moehlig RC (1946): Progeria with nanism and congenital cataracts in a five-year-old child. JAMA 132:640-642.

Patterson GT, Braun TW, Sotereanos GS (1982): Surgical correction of the dentofacial abnormality in Hallermann-Streiff syndrome. J Oral Maxillofac Surg 40:380-384.

Pious D, Millis AJT, Sabo K (1975): In vitro growth rates in primary cellular growth deficiency syndromes. Pediatr Res 9:279.

Ponte F (1962): Further contributions to the study of the syndrome of Hallermann and Streiff. Ophthalmologica 143:399-408.

Ravindran R, Stoops CM (1979): Anesthetic management of a patient with Hallermann-Streiff syndrome. Anesth Analg 58:254-255.

Riley RW, Powell NB, Guilleminault C (1987): Current surgical con- cepts for treating obstructive sleep apnea syndrome. J Oral Maxillofac Surg 45:149-157.

Riley RW, Powell NB, Guilleminault C (1989): Inferior mandibular osteotomy and hyoid myotomy suspension for obstruction sleep apnea: a review of 55 patients. J Oral Maxillofac Surg 47:159-164.

Roberts FG, Pruzansky S, Aduss H (1975): An X-radiocephalometric study of mandibulofacial dysostosis in man. Arch Oral Biol20265- 281.

Ryan CF, Lowe AA, Fleetham JA (1990): Nasal continuous positive airway pressure (CPAP) therapy. Clin Pediatr 29:122-124.

Sataloff RT, Roberts BR (1984): Airway management in Hallermann- Streiff syndrome. Am J Otolaryngol 5:64-67.

Schanzlin DJ, Goldberg DB, Brown SI (1980): Hallermann-Streiff syndrome associated with sclerocornea, aniridia, and a chromo- somal abnormality. Am J Ophthalmol 90:411-415.

Schmidt-Nowara WW (1984): Continuous positive airway pressure for long-term treatment of sleep apnea. Am J Dis Child 138:82-84.

Schondel A (1943): Two cases of progeria complicated by microph- thalmus. Acta Paediatr 30:286-304.

Sclaroff A, Eppley BL (1987): Evaluation and surgical correction of the facial skeletal deformity in Hallermann-Streiff syndrome. Int J Oral Maxillofac Surg 16:738-744.

Scoppetta C, Alanese A, Caltagirone C (1979): Oligophrenia in the Hallermann-Streiff syndrome. J Neurol 220:211-214.

Slootweg PJ, Huber J (1984): Dento-alveolar abnormalities in oculomandibulodyscephaly (Hallermann-Streiff syndrome). J Oral Pa- tho1 13:147-154.

Srivastava S et a1 (1966): Mandibulo-oculo-facial dyscephaly. Br J Ophthalmol 58543-549.

Steel HH, AkGarnia BA, Lang BD (1975): Bilateral dislocation of the hip in Hallermann-Streiff syndrome: A case report. J Bone Jt Surg 57A:1002-1005.

Steele RW, Bass J W (1970): Hallermann-Streiff syndrome: Clinical and prognostic considerations. Am J Dis Child 120:462-465.

Streiff EB (1950): Dysmorphie mandibulo-faciale (t6te d’oiseau) et al- teration oculaires. Ophthalmologica 120:79-83.

Sugar A, Bigger JF, Podos SM (1971): Hallermann-Streiff-Franqois syndrome. J Pediatr Ophthalmol 8:234-238.

Suzuki Y, Fuj i T, Fukuyama Y (1970): Hallermann-Streiff syndrome. Dev Med Child Neurol 12:496-506.

Teuscher M (1974): Beitrag zum Ullrich-Fremerey-Dohna oder Fran- qois-Syndrom. Acta Ophthalmol 52534-540.

Ullrich 0, Fremerey-Dohna H (1953): Dyskephalie mit Cataracta congenita und Hypotrichose als typischer Merkmalskomplex. Oph- thalmologica 125:73-90, 144-154.

Van Balen ATM (1961): Dyscephaly with microphthalmos, cataract and hypoplasia of the mandible. Ophthalmologica 14153-63.

Van Balen ATM (1985): Franqois’ syndrome: an intermediate between mandibulofacial and craniofacial dysostosis. Ophthal Paediatr Genet 659-62.

Walbaum R, Woilliez M, Franqois P, Mayolle P (1968): Le syndrome de Hallermann-Streiff-Franqois. Pediatrie 23:789-794.

Wolter JR, Jones DH (1965): Spontaneous cataract absorption in Hallermann-Streiff syndrome. Ophthalmologica 150:401-408.

Zolog N (1967): Syndrome dyscephalique de Franqois avec tetralogie de Fallot. Rev Oto-Neuro-Ophthal 39:65.

hallermann–streiff syndrome: a review

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