Information on the following diseases can be found in the Related Disorders section of this report:

• Hutchinson-Gilford progeria syndrome
• Wiedemann-Rautenstrauch syndrome
• Seckel syndrome
• Osteodysplastic bird-headed dwarfism types I, II, and III

Associated symptoms and signs may vary greatly in range and severity from case to case. However, the principal features of Hallermann-Streiff syndrome include malformation of the skull (cranium) and certain bones of the face (known as dyscephaly); associated craniofacial abnormalities; ocular defects; dental anomalies; and/or short stature with proportionate limb length (proportionate short stature). In many cases, additional abnormalities are also present.

Many affected infants have an unusually shaped skull, with abnormal shortness of the head (brachycephaly) and prominence of the forehead and/or sides of the skull (frontal and/or parietal bossing). In some cases, the head may also be relatively small (microcephaly) and the cheekbones may be underdeveloped (malar hypoplasia). In addition, there is typically abnormal widening or gaping of the fibrous joints (sutures) between certain bones of the skull and delayed closure of the two "soft spots" (fontanelles) at the front and back of the cranium.

Affected individuals also often have a disproportionately small face; a high, narrow roof of the mouth (palate); and/or a small lower jaw (micrognathia) and receding chin. The nose is typically narrow and pointed; is often curved, with small nostrils and underdeveloped nasal cartilage; and tends to become "parrotlike" with age. In addition, many with the syndrome have abnormally sparse hair (hypotrichosis), particularly of the scalp. However, the eyelashes, eyebrows, beard, pubic hair, and hair under the arms (axillae) may also be affected. Degenerative skin changes (atrophy) are also often present that are largely limited to the scalp and nose. Due to such changes, the skin in such regions may appear unusually taut and thin, and regional blood vessels may seem unusually pronounced.

Certain craniofacial abnormalities associated with the disorder, such as small nostrils and glossoptosis, may cause narrowing and obstruction of the upper air passages, particularly during the newborn period and infancy. Glossoptosis refers to downward displacement or retraction of the tongue that may occur secondary to abnormal smallness of the lower jaw (micrognathia). A narrow upper airway may lead to feeding, swallowing, and/or breathing difficulties; severe early respiratory infections; inflammation of the lungs (pneumonia); episodes in which there is absence of spontaneous breathing (apnea); anesthetic complications; and potentially life-threatening complications in severe cases. Abnormal softening of cartilage of the windpipe (tracheomalacia) has also been reported in some cases, which may further complicate swallowing and breathing difficulties. In addition, there have also been reports in which respiratory insufficiency (e.g., due to a narrow upper airway and/or tracheomalacia) has resulted in enlargement and strain of the lower right chamber (ventricle) of the heart (cor pulmonale) and possibly the left ventricle, leading to heart failure. Heart failure is an inability of the heart to pump enough blood to meet the body's requirements for oxygen and other nutrients.

Most individuals with Hallermann-Streiff syndrome also have ocular abnormalities. The most common ocular finding is clouding (opacity) of the lenses of both eyes at birth (congenital bilateral cataracts). According to reports in the medical literature, the cataracts, which consist of whitish, milky lens masses, may gradually be spontaneously absorbed (spontaneous cataract absorption) in some cases. Many individuals with the disorder also have abnormal smallness of both eyes (bilateral microphthalmia) of varying severity. In addition, in some cases, additional ocular defects may also be present, such as abnormal deviation of one eye in relation to the other (strabismus); involuntary, rapid, rhythmic eye movements (nystagmus); unusual blueness of the "whites" of the eyes (blue sclera); abnormally elevated pressure of the fluid of the eyes (glaucoma); downslanting eyelid folds (palpebral fissures); and/or other findings. Such ocular defects may result in varying degrees of visual impairment or, in some cases, blindness.

Hallermann-Streiff syndrome is also frequently characterized by dental abnormalities. These may include the development of teeth before or shortly after birth (natal or neonatal teeth); malformed teeth; improper contact of the teeth of the upper jaw with those of the lower jaw (malocclusion); and/or persistence of the primary (deciduous) teeth. Additional dental defects may also be present, such as absence of certain teeth; extra (supernumerary) teeth; and/or severe, early tooth decay (dental caries).

In approximately one third of reported cases, infants with Hallermann-Streiff syndrome are born prematurely and/or have a low birth weight. About two thirds of affected individuals have growth deficiency after birth (postnatally) and associated proportionate short stature.

In some cases, additional physical abnormalities have also been reported in association with the disorder. Some affected males may have abnormally decreased testicular function (hypogonadism); undescended testes (cryptorchidism); and/or abnormal placement of the urinary opening, such as on the underside of the penis (hypospadias). Skeletal abnormalities have also been reported in some cases, such as widely flared shoulder blades (winged scapula); abnormal inward or sideways curvature of the spine (lordosis or scoliosis); abnormal depression of the breastbone (funnel chest [pectus excavatum]); webbing of certain fingers and/or toes (syndactyly); and/or other features. Some affected infants may also have vitiligo, a condition characterized by irregular patches of skin that lack pigmentation. In addition, in rare cases, various structural heart malformations (congenital heart defects) have been reported. Such congenital heart defects have included an abnormal opening in the partition (septum) that separates the lower or upper chambers of the heart (ventricular or atrial septal defects) or abnormal narrowing of the opening between the pulmonary artery and the right ventricle of the heart (pulmonary stenosis).

In most cases, children with the disorder have normal intelligence. However, mental retardation has been reported in approximately 15 percent of cases. In addition, in rare instances, neurologic abnormalities have been noted, including hyperactivity; sudden episodes of uncontrolled electrical activity in the brain (seizures); and/or choreoathetosis, a condition characterized by abnormal, involuntary, irregular jerky motions and slow, writhing movements.
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In almost all reported cases, Hallermann-Streiff syndrome has appeared to occur randomly for unknown reasons (sporadically), most likely representing a new spontaneous genetic change (mutation). Investigators report that there is little evidence for recessive disease transmission in such cases.

Human traits, including the classic genetic diseases, are the product of the interaction of two genes, one received from the father and one from the mother. In autosomal recessive disorders, the condition does not appear unless a person inherits the same defective (mutated) gene for the same trait from each parent. If an individual receives one normal gene and one gene for the disease, the person will be a carrier for the disease but usually will not show symptoms. The risk of transmitting the disease to the children of a couple, both of whom are carriers for a recessive disorder, is 25 percent. Fifty percent of their children risk being carriers of the disease but generally will not show symptoms of the disorder. Twenty-five percent of their children may receive both normal genes, one from each parent, and will be genetically normal (for that particular trait). The risk is the same for each pregnancy.
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Hallermann-Streiff syndrome was first described in the medical literature in 1893. The disorder was named for two investigators who later independently reported cases of the syndrome (Hallermann W, 1948; Streiff EB, 1950), recognizing it as a distinct disease entity.

Hallermann-Streiff syndrome appears to affect males and females in relatively equal numbers. More than 150 cases have been reported in the medical literature.
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Symptoms of the following disorders can be similar to those of Hallermann-Streiff Syndrome. Comparisons may be useful for a differential diagnosis:

Hutchinson-Gilford progeria syndrome is a very rare progressive disorder of childhood characterized by premature aging (progeria); growth delays occurring in the first year of life resulting in short stature and low weight; deterioration of the layer of fatty tissue beneath the skin (subcutaneous lipodystrophy); and characteristic craniofacial abnormalities including an abnormally small face, underdeveloped jaw (micrognathia), unusually prominent eyes, and/or a small, "beak-like" nose. In addition, during the first year or two of life, scalp hair, eyebrows, and eyelashes may become sparse, and veins of the scalp may become unusually prominent. Additional symptoms and physical findings may include joint stiffness, repeated non-healing fractures, a progressive aged appearance, delays in tooth eruption (dentition), and/or malformation and crowding of the teeth. Individuals with the disorder typically have normal intelligence. In most cases, affected individuals develop premature, widespread thickening and loss of elasticity of arterial walls (arteriosclerosis), potentially resulting in life-threatening complications. Hutchinson-Gilford progeria syndrome is thought to be due to a spontaneous change in genetic material (mutation) or, in some cases, may be inherited as an autosomal dominant genetic trait. (For more information on this disorder, choose "Hutchinson Gilford" as your search term in the Rare Disease Database.)

Wiedemann-Rautenstrauch syndrome (also known as neonatal progeroid syndrome) is an extremely rare genetic disorder characterized by an aged appearance at birth (neonatal progeroid appearance); growth delays before and after birth (prenatal and postnatal growth retardation); and the deficiency or absence of the layer of fatty tissue under the skin (subcutaneous lipoatrophy), causing the skin to appear abnormally thin, fragile, and wrinkled. In addition, for reasons that are not understood, abnormal deposits of fat may accumulate around the buttocks, the areas around the genitals and the anus (anogenital area), and the area between the ribs and the hips (flanks). Affected infants and children also have distinctive malformations of the head and facial (craniofacial) area including an unusual prominence of the forehead (frontal bossing) and the sides of the skull (parietal bossing), causing the head to appear abnormally large (pseudohydrocephalus); unusually small, underdeveloped (hypoplastic) bones of the face and abnormally small facial features; a small "beak-shaped" nose that becomes more pronounced with advancing age; and/or sparse scalp hair, eyebrows, and/or eyelashes. Most infants and children with Wiedemann-Rautenstrauch syndrome also have unusually thin arms and legs; abnormally large hands and feet; progressive neurological and neuromuscular abnormalities; varying degrees of mental retardation; and severe delays in the acquisition of skills requiring the coordination of mental and muscular activities (psychomotor retardation). In addition, in many cases, affected infants and children are prone to repeated respiratory infections that may result in life-threatening complications. Wiedemann-Rautenstrauch syndrome is inherited as an autosomal recessive genetic trait. (For more information on this disorder, choose "Wiedemann Rautenstrauch" as your search term in the Rare Disease Database.)

Seckel syndrome is an extremely rare inherited disorder characterized by growth delays prior to birth (intrauterine growth retardation) resulting in low birth weight. Growth delays continue after birth (postnatal) resulting in short stature (dwarfism). Other symptoms and physical features associated with Seckel syndrome include an abnormally small head (microcephaly); varying degrees of mental retardation; and/or unusual characteristic facial features including "beak-like" protrusion of the nose. Other facial features may include abnormally large eyes, a narrow face, malformed ears, and/or an unusually small jaw (micrognathia). In addition, some affected infants may exhibit permanent fixation of the fifth fingers in a bent position (clinodactyly), malformation (dysplasia) of the hips, dislocation of a certain bone in the forearm (radial dislocation), and/or other physical abnormalities. Seckel syndrome is thought to be inherited as an autosomal recessive genetic trait. (For more information on this disorder, choose "Seckel" as your search term in the Rare Disease Database.)

Osteodysplastic bird-headed dwarfism, also known as osteodysplastic primordial dwarfism, is an extremely rare inherited disorder characterized by low birth weight, growth delays resulting in short stature (dwarfism), an unusually small head (microcephaly), and characteristic facial features including "beak-like" protrusion of the nose. Other characteristic facial features may include abnormally large eyes, an unusually small jaw (micrognathia) that is recessed farther back than normal (retrognathia), a narrow face, and/or low-set ears. In some cases, affected children may exhibit other abnormalities, such as mental retardation, skeletal deformities, and/or patchy areas of hair loss (alopecia) on the scalp. There are three types of osteodysplastic bird-headed dwarfism, designated type I, II, and III. They are distinguished according to slight differences in their sets of symptoms. Osteodysplastic bird-headed dwarfism types I, II, and III are all thought to be inherited as autosomal recessive genetic traits.

Diagnosis
Hallermann-Streiff syndrome may be suspected shortly after birth or during the first year of life by the identification of characteristic physical findings and symptoms. The diagnosis may be confirmed based upon a thorough clinical evaluation; a detailed patient history; and specialized tests (e.g., x-ray, ophthalmologic, and dental studies) that may help to detect and characterize certain abnormalities associated with the disorder. Some investigators suggest that the presence of congenital cataracts and/or unusually small eyes (microphthalmia) are important findings for the diagnosis of Hallermann-Streiff syndrome.

Treatment
The treatment of Hallermann-Streiff syndrome is directed toward the specific symptoms that are apparent in each individual. Treatment may require the coordinated efforts of a team of medical professionals, such as pediatricians, craniofacial surgeons, eye specialists (ophthalmologists), dental specialists, and/or other health care professionals.

In infants with feeding and respiratory difficulties, recommended early disease management may include monitoring of breathing; tracheostomy, or creation of an opening through the neck into the windpipe into which a tube is inserted, to help maintain an effective airway; various supportive measures to improve feeding and ensure sufficient intake of nutrients; and/or other measures. In addition, early surgical removal of cataracts is typically recommended to help preserve vision. However, some investigators indicate that the frequency of spontaneous cataract absorption (see "Symptoms") may be underestimated in those with Hallermann-Streiff syndrome, suggesting that it may potentially occur in up to 50 percent of untreated patients followed up through five years of age. Such physicians may advise waiting for possible spontaneous cataract absorption in selected cases, particularly for patients with significant microphthalmia. Further investigation is needed regarding the frequency of spontaneous cataract absorption and the implications concerning optimal treatment approaches.

In individuals with Hallermann-Streiff syndrome, recommended disease management may also include surgical reconstruction of certain craniofacial malformations (e.g., of the mandibular and nasal region) at the appropriate age. Some affected individuals may have a risk of anesthetic complications, since endotracheal intubation and laryngoscopy may be difficult due to upper airway obstruction. (Intubation may be required for the delivery of oxygen or anesthetic gases during surgery. A viewing tube [laryngoscope] is used before intubation to help identify the vocal cords. A breathing [endotracheal] tube is then passed through the mouth down the throat and into the windpipe.) This potential anesthetic risk must be taken into consideration by surgeons, anesthesiologists, and other health care workers when making decisions concerning surgery.

For some affected infants and children with heart defects, treatment with certain medications, surgical intervention, and/or other measures may also be recommended. In addition, in some cases, physicians may advise surgical intervention for other abnormalities associated with the syndrome. The specific surgical procedures performed will depend upon the size, nature, severity, and/or combination of the anatomical abnormalities, their associated symptoms, and other factors.

Early intervention is important to ensure that children with Hallermann-Streiff syndrome reach their potential. Special services that may be beneficial include special remedial education, special social support, physical therapy, and other medical, social, and/or vocational services.

Genetic counseling may also be of benefit for affected individuals and their families. Other treatment is symptomatic and supportive.
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Research on genetic disorders and their causes is ongoing. The National Institutes of Health (NIH) is sponsoring the Human Genome Project which is aimed at mapping every gene in the human body and learning why they sometimes malfunction. It is hoped that this new knowledge will lead to prevention and treatment of genetic and familial disorders in the future.

McKusick VA., ed. Online Mendelian Inheritance in Man (OMIM). Baltimore. MD: The Johns Hopkins University; Entry No: 234100; Last Update: 6/11/99.

TEXTBOOKS
Behrman RE, et al., eds. Nelson Textbook of Pediatrics. 16th ed. Philadelphia, Pa: W.B. Saunders Company; 2000:1917, 1919.

Jones KL. Smith’s Recognizable Patterns of Human Malformation. 5th ed. Philadelphia, Pa; WB Saunders Company; 1997:110.

Buyse ML. Birth Defects Encyclopedia. Dover, Mass: Blackwell Scientific Publications, Inc; 1990:1278-79.

Gorlin RJ, et al., eds. Syndromes of the Head and Neck. 3rd ed. New York, NY: Oxford University Press; 1990:306-08.

REVIEW ARTICLES
David LR, Finlon M, Genecov D, et al. Hallermann-Streiff syndrome: experience with 15 patients and review of the literature. 1999;10:160-68.

Vadiakas G, Oulis C, Tsianos E, et al. A typical Hallermann-Streiff syndrome in a 3 year old child. J Clin Pediatr Dent. 1995;20:63-68.

JOURNAL ARTICLES


JOURNAL ARTICLES
Rohrbach JM, Djelebova T, Schwering MJ, et al. Hallermann-Streiff syndrome: should spontaneous resorption of the lens opacity be awaited? Klin Monatsbl Augenheilkd. 2000;216:172-76.

Nicholson AD, Menon S. Hallerman-Streiff syndrome. J Postgrad Med. 1995;41:22-23.

de Fonseca MA, Mueller WA. Hallermann-Streiff syndrome: case report and recommendations for dental care. ASDC J Dent Child. 1994;61;334-37.

Cabral Castaneda FJ, Orozco Quiyono M, Ibarguengoitia Ochoa F et al. Hallermann-Streiff syndrome and pregnancy. A report of a case. Ginecol Obstet Mex. 1994;62;207-10.

Cohen MM Jr. Hallermann-Streiff syndrome: a review. Am J Med Genet. 1991;41: 488-99.

Robinow M. Respiratory obstruction and cor pulmonale in the Hallermann-Streiff syndrome. Am J Med Genet. 1991;41:515-16.

Harrod MJ, et al. Congenital cataracts in mother, sister, and son of a patient with Hallermann-Streiff syndrome: coincidence or clue? Am J Med Genet. 1991;41:500-02.