Hallermann-Streiff Syndrome

Description

Hallermann-Streiff syndrome is characterized by a typical skull shape (brachycephaly with frontal bossing), hypotrichosis, microphthalmia, cataracts, beaked nose, micrognathia, skin atrophy, dental anomalies, and proportionate short stature (Hallermann, 1948; Streiff, 1950; Francois, 1958). Mental retardation is present in a minority of cases (Gorlin et al., 1990).

Clinical Features

Hallermann (1948) and Streiff (1950) reported patients with dyscephaly, a 'bird-like' face, congenital cataracts, and microphthalmia. Francois (1958) identified similar reported cases with the additional features of hypotrichosis, skin atrophy, dental anomalies, and short stature.

Dental features were discussed by Caspersen and Warburg (1968).

Steele and Bass (1970) emphasized the lack of mandibular angle and hypoplasia of the clavicles and ribs.

Warburg (1971) emphasized that the diagnosis is doubtful in the absence of cataract or microphthalmia.

Cohen (1991) warned of the potential complications related to the narrow upper airway and suggested that snoring and/or daytime hypersomnolence are indications for sleep studies. Robinow (1991) also emphasized the risks of problems with upper airway obstruction in HSS, particularly in the neonatal period and in infancy. Obstruction may result from small nares and glossoptosis secondary to micrognathia and these may lead to cor pulmonale. Salbert et al. (1991) pointed to tracheomalacia as a complication of HSS that can lead to chronic respiratory insufficiency. Such resulted in biventricular cardiac failure and death at the age of 6 months.

Harrod and Friedman (1991) described a woman with HSS who had a son with congenital cataracts. Furthermore, her mother and a sister also had congenital cataracts. Harrod and Friedman (1991) were perplexed by these observations. The cataracts in the patient with HSS were no more severe than those in first-degree relatives who had only cataracts.

Radiologic findings in 5 cases and in the literature were reviewed by Christian et al. (1991).

Nosologic overlap with oculodentodigital dysplasia (ODDD; 164200) was discussed by Spaepen et al. (1991).

Congenital heart defects are rare in HSS. Imaizumi et al. (1994) reported what they believed to be the fourth case associated with congenital heart defect in a boy who had ventricular septal defects.

Mirshekari and Safar (2004) described a 26-year-old woman with Hallermann-Streiff syndrome. She had hypotrichosis, bird-like facies, atrophy of the skin (especially on the nose), abnormal dentition, and congenital bilateral cataracts, but was not dwarfed and did not have mental retardation.

Clinical Variability

Dennis et al. (1995) described a family in which a male infant who died neonatally and a female fetus who died at 29 weeks of gestation had an identical condition resembling Hallermann-Streiff syndrome. Long bones were slender with a few fractures, the skull was underossified, and the face was characteristic of HSS. Bilateral cataracts were identified in the male. They regarded the condition as a severe and lethal form of HSS.

Inheritance

Forsius and de la Chapelle (1964) found normal chromosomes in 2 cases.

Familial cases were reported by Bueno-Sanchez (1966) who found this syndrome in 2 of 3 sibs from a consanguineous marriage, supporting autosomal recessive inheritance. Karyotypes were normal.

Fraser and Friedmann (1967) supported dominant inheritance with almost all cases being the result of fresh mutation. They pointed to the probable cases in father and daughter reported by Guyard et al. (1962). However, the father was married to a distant relative; hence, this may have been an instance of pseudodominance.

Steele and Bass (1970) reviewed 50 published cases. Two patients had reproduced: an affected woman gave birth to 2 normal children (Ponte, 1962) and, as noted earlier, an affected man married to a distantly related woman sired an affected daughter (Guyard et al., 1962).

Both of monozygotic twins were affected in the report of Van Balen (1961).

Francois (1982) quoted data indicating a normal sex ratio (42 males, 46 females) and a high frequency of parental consanguinity. He knew of 2 instances of concordant monozygotic twins and at least 10 families with 2 or more cases. In all but 3 of these, the affected persons were sibs.

Koliopoulos and Palimeris (1975) observed 5 cases in 3 generations with male-to-male transmission.

In a review, Cohen (1991) pointed out that all cases have been sporadic, that the disorder has been both concordant and discordant in monozygotic twins, and that an affected female with 2 normal children was reported by Ponte (1962). He stated: 'I cannot accept any of the familial cases recorded to date.'

Nomenclature

To call this Francois syndrome (Battin et al., 1976) runs a risk of confusion with another Francois syndrome (221800).