Journal of Pediatric Ophthalmology and Strabismus

Hallermann-Streiff-Francois Syndrome

Alan Sugar, MD; John F Bigger, MD; Steven M Podos, MD

Abstract

Hallermann-Streiff-Francois syndrome, a complex of skeletal and ocular anomalies, was described partially by Aubry ' in 1893 and presented with greater emphasis on ocular findings by Hallermann 2 in 1948 and Streiff3 in 1950. Ullrich and FremereyDohna 4 reported it as a distinct entity in 1953 and Francois 5 elucidated the typical features and collected 22 cases in 1958. To date, more than 50 cases have appeared in the literature as Francois, Hallermann-Streiff, or FrancoisHallermann-Streiff syndrome.6,7

The prompt recognition of this entity may alter favorably the poor prognosis often suggested by the multiple congenital lesions. A patient demonstrating typical features and unnecessarily delayed ophthalmic therapy is presented herein.

Case History

Steven R., a nine-year-old white boy, was referred for evaluation of multiple ocular defects. He was the product of a full-term pregnancy and normal delivery to a 17-year-old mother and 21 -year-old father. Birth weight was 8 pounds; and length, 1 8 1/2 inches. No abnormalities were recorded at birth and the child left a delivery clinic the same day. Because of "snorting" respirations the child was seen by a pediatrician on the third day of life, and a diagnosis of "tumor under the tongue" was made. At age six weeks, bilateral cataracts were noted, and the child was referred to a pediatric hospital. The parents were told that no treatment was indicated as the child would not live beyond infancy. At the age of six months, enlarging head size was noted and a presumptive diagnosis of hydrocephalus with "brain damage" was made. A shunting procedure was recommended but declined by the parents. Except for frequent ear infections and a left inguinal herniorrhaphy at age eight years, he required no further medical attention. He weighed 10 pounds at age one year and 16 pounds at age five years. He walked and spoke his first words at three years. Deciduous dentition began at age two years; front teeth were lost at five years and never replaced. The child had never been to school. A psychologic evaluation at age seven years demonstrated an intelligence quotient of 70-80 with evaluation hindered by visual deficit. At the time of the present hospitalization, his parents felt that he had good mobility and no difficulty recognizing large, closely held objects.

There was no family history of congenital defects or short stature. The mother, aged 26, was 5'2" tall, the father, aged 30, 6'2" tall. The only sibling, a 10year-old male was 4'6" tall and had no known defects. No family history of glaucoma or cataracts was elicited. A maternal grandmother was diabetic. There was no history of consanguinity, although both paternal and maternal families came from the same rural community.

Physical examination showed a height of 97.5 cm (3'8") (Fig. 1), markedly below the third percentile for age nine, but in the 50th percentile for a threeyear-old; weight, 26 pounds; and head circumference, 50 cm, in the second percentile for his age.' The head (Fig. 2) was brachycephalic with frontal and occipital bossing. Scalp hair was scant and patchy, eyebrows absent, and lid cilia rare; forehead folds were prominent, and the skin of the forehead and scalp was atrophic. The ears were lowset but of normal configuration; bilateral tympanic membrane perforations were present The nose was small and beaked. The mouth was narrow with a high arched palate, edentulous maxilla, and marked micrognathia. Examination of the chest revealed mild pectus excavatum but no cardiopulmonary abnormalities. The genitalia appeared normal but the testes were not palpable in the scrotum or inguinal canal. Partial syndactyly of the third and fourth toes was present bilaterally, and the third and…

Hallermann-Streiff-Francois syndrome, a complex of skeletal and ocular anomalies, was described partially by Aubry ' in 1893 and presented with greater emphasis on ocular findings by Hallermann 2 in 1948 and Streiff3 in 1950. Ullrich and FremereyDohna 4 reported it as a distinct entity in 1953 and Francois 5 elucidated the typical features and collected 22 cases in 1958. To date, more than 50 cases have appeared in the literature as Francois, Hallermann-Streiff, or FrancoisHallermann-Streiff syndrome.6,7

The prompt recognition of this entity may alter favorably the poor prognosis often suggested by the multiple congenital lesions. A patient demonstrating typical features and unnecessarily delayed ophthalmic therapy is presented herein.

Case History

Steven R., a nine-year-old white boy, was referred for evaluation of multiple ocular defects. He was the product of a full-term pregnancy and normal delivery to a 17-year-old mother and 21 -year-old father. Birth weight was 8 pounds; and length, 1 8 1/2 inches. No abnormalities were recorded at birth and the child left a delivery clinic the same day. Because of "snorting" respirations the child was seen by a pediatrician on the third day of life, and a diagnosis of "tumor under the tongue" was made. At age six weeks, bilateral cataracts were noted, and the child was referred to a pediatric hospital. The parents were told that no treatment was indicated as the child would not live beyond infancy. At the age of six months, enlarging head size was noted and a presumptive diagnosis of hydrocephalus with "brain damage" was made. A shunting procedure was recommended but declined by the parents. Except for frequent ear infections and a left inguinal herniorrhaphy at age eight years, he required no further medical attention. He weighed 10 pounds at age one year and 16 pounds at age five years. He walked and spoke his first words at three years. Deciduous dentition began at age two years; front teeth were lost at five years and never replaced. The child had never been to school. A psychologic evaluation at age seven years demonstrated an intelligence quotient of 70-80 with evaluation hindered by visual deficit. At the time of the present hospitalization, his parents felt that he had good mobility and no difficulty recognizing large, closely held objects.

There was no family history of congenital defects or short stature. The mother, aged 26, was 5'2" tall, the father, aged 30, 6'2" tall. The only sibling, a 10year-old male was 4'6" tall and had no known defects. No family history of glaucoma or cataracts was elicited. A maternal grandmother was diabetic. There was no history of consanguinity, although both paternal and maternal families came from the same rural community.

Physical examination showed a height of 97.5 cm (3'8") (Fig. 1), markedly below the third percentile for age nine, but in the 50th percentile for a threeyear-old; weight, 26 pounds; and head circumference, 50 cm, in the second percentile for his age.' The head (Fig. 2) was brachycephalic with frontal and occipital bossing. Scalp hair was scant and patchy, eyebrows absent, and lid cilia rare; forehead folds were prominent, and the skin of the forehead and scalp was atrophic. The ears were lowset but of normal configuration; bilateral tympanic membrane perforations were present The nose was small and beaked. The mouth was narrow with a high arched palate, edentulous maxilla, and marked micrognathia. Examination of the chest revealed mild pectus excavatum but no cardiopulmonary abnormalities. The genitalia appeared normal but the testes were not palpable in the scrotum or inguinal canal. Partial syndactyly of the third and fourth toes was present bilaterally, and the third and fourth metacarpals were shortened.

Fig. 1: General appearance: note short stature, dyscephaly, esotropia, and typical fades.

Fig. 1: General appearance: note short stature, dyscephaly, esotropia, and typical fades.

Fig. 2: Lateral view demonstrating dyscephaly with bird face and micrognathia, hypotrichosis and skin atrophy.

Fig. 2: Lateral view demonstrating dyscephaly with bird face and micrognathia, hypotrichosis and skin atrophy.

Visual acuity could not be measured accurately although small objects were readily identified when held within a few inches of either eye. Vision was subjectively improved by +12.00 diopter spheres bilaterally. There was a slight downward slant of the palpebral fissures. The sclerae were blue and corneal diameter measured 10 mm bilaterally. The pupils were irregular, measured 2 mm bilaterally, and reacted slowly. A 20 prism diopter right esotropia with pendular and jerk nystagmus in all fields of gaze was present. The corneae were clear and the anterior chambers deep and clear. The irides were blue with subtle Brushfield spots. Dense posterior synechiae bound the iris to dense membranous cataracts which appeared to consist of thickened capsules with partially resorbed lens cortex (Fig. 3). The fundi could not be visualized. Applanation tensions were right eye 20 and left eye 22 mm Hg; gonioscopic evaluation was normal.

X-rays of the skull revealed increased height and length with parietal bossing. The sella was "J" shaped, the fa] ? was calcified, and a moderate degree of platybasia was present. The mandible was markedly hypoplastic and the maxilla and zygoma less so (Fig. 4 and 5). Long bones and joints were normal except for shortened ulnae and third metacarpals. Bone age was nine years.

Complete blood count and urinalysis results were normal; VDRL was nonreactive. Findings from electrolytes, calcium, total proteins, bilrubin, and BUN studies were normal. Alkaline phosphatase and SGOT were mildly elevated. Urinary 17-hydroxy corticosteroids were 2.6, 2.6, and 7.1 mg/24 hours. Under general anesthesia a needling of the membrane in the left eye was performed by the Sato technique* The postoperative course was complicated by a moderate iritis lasting four weeks. Six weeks postoperatively, vision was at least finger counting at 8 feet with a +20.00 diopter sphere. A good pupillary opening was present (Fig. 6). The fundus showed poorly defined disc margins with a small optic nervehead. A yellow-gray band of subretinal pigment extended vertically through the macula. Intraocular pressures by Schiotz tonometry were right eye 30 mm Hg and left eye 26 mm Hg.

Discussion

The characteristic features of the Hallermann-Streiff-Francois syndrome give such patients an unmistakable appearance. There are, according to Francois,* seven major features: (1) dyscephaly and bird face, including micrognathia; (2) dental anomalies; (3) proportionate dwarfism; (4) hypotrichosis; (5) skin atrophy of the head and nose; (6) bilateral microphthalmos; and (7) congenital cataracts. The presence and degree of such features are variable. Additional features may include syndactyly, high-arched palate, platybasia, open cranial sutures and fontanelles, spina bifida, hypogenitalism, and cryptorchidism.6,10

A variety of ocular lesions are seen. In addition to microphthalmos and congenital cataracts a frequent feature is spontaneous absorption of the cataractous lens.*'""13 This feature can lead to chronic iridocyclitis which may be due to hypersensitivity to lens substance. Pathologic confirmation of such a phacoanaphylactic response is presented by Wolter and Jones.13 Nystagmus and strabismus are frequent features, probably secondary to the severe visual deficit. Inconstant features such as anti-mongoloid palpebral fissures, blue sclerae, keratoglobus, anterior synechiae, iris atrophy, iris coloboma, posterior synechiae, and disc coloboma are described.5'""14 Other manifestations include chorioretinal and peripapillary choroidal atrophy ls and retinal folds." A vertical subretinal pigment band, as seen in our patient, is reported by Carones.17

Glaucoma occurs in patients with Hallermann-Streiff-Francois syndrome.""13 G? all seven reported patients the glaucoma appears to have been secondary to granulomatous anterior uveitis with formation of extensive peripheral anterior synechiae. No anterior synechiae are present in our case. Microcornea possibly may play a role, but the hazard of glaucoma is less if surgical intervention takes place before spontaneous release of lens material.12

Fig. 3: Right eye: the cataract is partially resorbed and bound to iris by posterior synechiae.

Fig. 3: Right eye: the cataract is partially resorbed and bound to iris by posterior synechiae.

Fig. 4: Skull x-ray, posterior - anterior, showing parietal bossing, calcified falx, mandibular hypoplasia and absent secondary dentition.

Fig. 4: Skull x-ray, posterior - anterior, showing parietal bossing, calcified falx, mandibular hypoplasia and absent secondary dentition.

There are no characteristic laboratory features. Low urinary 17-hydroxy and 17ketosteroid excretion and increased serum gamma globulin are mentioned in a few instances.5 It is of interest that pituitary function, when studied, is found to be normal. Normal response of growth hormone to arginine stimulation rules out growth hormone deficiency as a factor in short stature.'

Fig. 5: Skull x-ray, lateral, showing "J" shaped sella, hypoplastic maxilla and zygoma, and moderate plat y bas ?a.

Fig. 5: Skull x-ray, lateral, showing "J" shaped sella, hypoplastic maxilla and zygoma, and moderate plat y bas ?a.

Fig. 6: Left eye, postoperatively; note good pupillary opening.

Fig. 6: Left eye, postoperatively; note good pupillary opening.

Although the etiology of this entity is unknown, the presence of a single gene mutation, as suggested by Falls," appears most likely. Abnormality in size of a 13-15 chromosome is described ,7 and refuted.15 It is suggested that the gene locus may occur on the same chromosome as that for neurofibromatosis." One report documents two sets of twins, one pair with both siblings involved and one with one member involved.6 Because of hypogonadism most patients do not reproduce but there is at least one mother with mild features of this syndrome.15 The presence of several features in a father and daughter reported by Guyard et al w suggests a dominant mode of transmission, but consanguinity in that case mades this indefinite.

Some patients may succumb in infancy to respiratory infections ,0''5 and pulmonary insufficiency, possibly related to airway obstruction and abnormal thoracic compliance.6 Many patients, however, are discovered as older children or adults, the oldest being 55 years old.2 It appears, therefore, that those afflicted with the Hallermann-Streiff-Francois syndrome may have a normal life span. A longer period of follow-up is necessary before the true natural history of the disease is known.

Summary

A nine year old boy with classic features of the Hallermann-Streiff-Francois syndrome presented with characteristic bilateral microphthalmos and spontaneously resorbed congenital cataracts. In addition, elevated intraocular pressures and a subretinal pigment band were found. The diagnosis of this syndrome should be made on the basis of the patient's appearance and early aggressive therapy initiated as life span may be normal.

References

1. Aubry M.: Variete d'alopecie congenitale; alopecie suturale. Ann Dermat et Syph 4:899, 1893.

2. Hallermann W: Vogelgesicht und Cataracta congenita. Klin Monatsbl Augenh 113:315. 1948.

3. Streiff EB: Dysmorphic man ibu lo- faciale (tete d'oiseau) et alterations oculaires. Ophthalmologic 120:79, 1957.

4. Ullrich O, Fremerey-Dohna H: Dyskephalie mit Cataracta congenita und Hypotrichose als typischer Merkmalskomplex Ophthalmologica 125:73. 144, 1953.

5. Francois J: A new syndrome, dyseephalia with bird face and dental anomalies, nanism, hypotrichosis, cutaneous atrophy, microphthalmia, and congenital cataract. Arch Ophth 60:842, 1958.

6. Steele R, Bass J: Hallermann-Streiff syndrome, clinical and prognostic considerations. Amer J Dis Child 120:462, 1970.

7. Torres Marty L, Dolcet L: Franco is-Hal lermann-Streiff syndrome. Arch Soc Oftal Hisp Amer 24:474, 1964.

8. Nelson W. led): Textbook of Pediatrics. Philadelphia, WB Saunders, ? 42, 48, 1964.

9. Yamashita T,Drews R: Discission with the aid of a fixation needle (Sato technique). Amer J Ophth 49:978, 1960.

10. Smith D. Recognizable Patterns of Human Malformations. Philadelphia, WB Saunders, ? 72, 1970.

11. Falls H, Schull W: Hallermann-Streiff syndrome, a dyscephaly with congenital cataracts and hypotrichosis. Arch Ophth 63:409, 1960.

12. Hopkins D, Horan E: Glaucoma in the Hallermann-Streiff syndrome. Brit J Ophth 54:416, 1970.

13. Wolter J, Jones D: Spontaneous cataract absorption in Hallermann-Streiff syndrome. Ophthalmologica 150:401, 1965.

14. Guyard M, Perdriel G, Ceruti F: Sur deux cas de syndrome dyscephalique a tete d'oiseau. Bull Soc Ophth France 62:443, 1962.

15. Hoefnagel D, Benirschke K: Dyscephalia mandibulo-oculo-facialis. Arch Dis Child 40:57, 1965.

16. Ide C, Webb R: Hallermann-Streiff syndrome. Amer J Ophth 67:151, 1969.

17. Carones A: Syndrome dyscephalique de Francois. Ophthalmologica. 142:510, 1961.

10.3928/0191-3913-19711101-05

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