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N/A

NORD is very grateful to John M. Graham, Jr., MD, ScD, Director of Clinical Genetics and Dysmorphology, Cedars-Sinai Medical Center, for assistance in the preparation of this report.

Synonyms of N/A

  • Francois dyscephaly syndrome
  • Hallermann Streiff Fran├žois syndrome
  • HSS
  • oculomandibulodyscephaly with hypotrichosis
  • oculomandibulofacial syndrome

Disorder Subdivisions

  • No subdivisions found.

General Discussion

Summary
Hallermann-Streiff syndrome (HSS) is a rare genetic disorder that is primarily characterized by distinctive malformations of the skull and facial (craniofacial) region; sparse hair (hypotrichosis); eye abnormalities; dental defects; degenerative skin changes (atrophy), particularly in the scalp and nasal regions; and proportionate short stature. Characteristic craniofacial features include a short, broad head (brachycephaly) with an unusually prominent forehead and/or sides of the skull (dyscephaly); a small, underdeveloped lower jaw (hypoplastic mandible); a narrow, highly arched roof of the mouth (palate); and a thin, pinched, tapering nose. Many affected individuals also have clouding of the lenses of the eyes at birth (congenital cataracts or corneal stromal opacities); unusually small eyes (microphthalmia); and/or other ocular abnormalities. Dental defects may include natal or neonatal teeth, absent permanent teeth (hypodontia or partial adontia), abnormal tooth development resulting in short roots and early loss of teeth, and/or improper alignment of teeth. In almost all cases, HSS has appeared to occur randomly for unknown reasons (sporadically), and this syndrome is thought to be the result of a new change to genetic material (mutation).

Introduction
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, recognizing it as a distinct disease entity.

Symptoms

Associated symptoms and signs vary greatly in range and severity from case to case. The principal features of Hallermann-Streiff syndrome include abnormalities of the skull (cranium) and certain bones of the face (known as dyscephaly); distinctive facial features; ocular defects; dental anomalies; and/or 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 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) with receding chin (retrognathia). The nose is typically quite narrow and pointed; with a narrow nasal bridge, small nostrils and underdeveloped nasal cartilage that tends to become more convex (beaked) with age. The underdevelopment of the jaw and nose may result in upper airway obstruction and breathing difficulties in young children. In addition, many people with this syndrome have very sparse hair (hypotrichosis), particularly of the scalp, eyelashes, eyebrows, beard, pubic hair, and hair under the arms (axillae). Degenerative skin changes (atrophy) are also often present and largely limited to the scalp and nose. Due to such changes, the skin in these regions may appear unusually taut and thin, and regional blood vessels may seem unusually pronounced.

The craniofacial abnormalities associated with the disorder, such as small nostrils and glossoptosis, can cause obstruction of the upper airway, 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; 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 as well, 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 HSS 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 spontaneously resolve (spontaneous cataract absorption) in some cases. Many individuals with this disorder also have abnormal smallness of both eyes (bilateral microphthalmia) of varying severity and/or unusually deep-set eyes (enophthalmos). As a result of these small deeply-seated eyes, patients may appear to have small, droopy eyelids (blepharoptosis). The edges of the eyelids may appear to turn inwards, particularly on the lower side (lower lid entropion) so that the eyelashes rub against the eye surface (cornea) leading to irritation, erosions and corneal opacities. Some eye experts have noted similar patterns of corneal stromal opacities in these patients, suggesting this might be a hallmark feature of this condition. 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); down-slanting eyelid folds (palpebral fissures); malformed orbital bones and/or other findings. Such ocular defects may result in varying degrees of visual impairment or, in some cases, blindness.

Hallermann-Streiff syndrome is frequently characterized by dental abnormalities. These may include the development of teeth before or shortly after birth (natal or neonatal teeth), which may be misdiagnosed as supernumerary teeth. There is also delayed eruption of teeth, abnormal tooth development, with severely undeveloped roots leading to early loss of permanent teeth and partially developed crowns, improper contact between the teeth of the upper jaw and those of the lower jaw (malocclusion), and/or persistence of the primary (deciduous) teeth. Additional dental defects may include absence of permanent teeth, extra (supernumerary) teeth, and/or severe, early tooth decay (dental caries).

In approximately one third of reported cases, infants with HSS are born prematurely and/or have a low birth weight. About two thirds of affected individuals have growth deficiency after birth 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 of the penis (hypospadias). Skeletal abnormalities have also been reported in some cases, such as widely flared shoulder blades (winged scapula), abnormal curvature of the spine (lordosis or scoliosis), abnormal depression of the breastbone (pectus excavatum), and/or webbing of fingers and/or toes (syndactyly). 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 this disorder have normal intelligence; however, intellectual disability has been reported in approximately 15 percent of cases. 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. With more patients undergoing MRI studies, various structural abnormalities of the brain have been reported. One as such case showed the absence of the corpus callosum (the thick band of nerve fibers that connects the right and left halves of the brain).

Causes

In almost all reported cases, Hallermann-Streiff syndrome has occurred randomly for unknown reasons (sporadically), most likely due to a new spontaneous dominant genetic change (mutation). There have been reports of patients with this disorder reproducing successfully and bearing multiple normal children. From families with an affected child, there is little evidence for this being a recessively inherited disorder in which both parents are carriers (normal looking but carry the mutation). Therefore, the mode of inheritance of this disorder remains elusive making it difficult to determine the exact recurrent risk.

Affected Populations

Hallermann-Streiff syndrome appears to affect males and females in relatively equal numbers. More than 150 cases have been reported in the medical literature.

Related Disorders

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 due to a de novo heterozygous mutation in the lamin A gene (LMNA) on chromosome 1q22. (For more information on this disorder, choose "Hutchinson Gilford" as your search term in the Rare Disease Database) Other disorders with less severe, but overlapping features include mandibuloacral dysplasia, an autosomal recessive disorder, which is caused by different bmutations in the LMNA gene, and Werner syndrome, an autosomal recessive progeroid syndrome caused by autosomal recessive mutations in the RECQL2 gene.

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 deficiency); and deficient or absent fatty tissue under the skin (subcutaneous lipoatrophy), causing the skin to appear abnormally thin, fragile, and wrinkled. In addition abnormal deposits of fat may accumulate around the buttocks, flanks, genitals and anus (anogenital area). Affected infants and children have distinctive facial features with unusual prominence of the forehead (frontal bossing) and the sides of the skull (parietal bossing), causing the head to appear 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 have unusually thin arms and legs; abnormally large hands and feet; progressive neurological and neuromuscular abnormalities; varying degrees of intellectual disability; and severe delays in the acquisition of skills requiring the coordination of mental and muscular activities (psychomotor retardation). In addition, 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 autosomal recessive disorder characterized by growth deficiency prior to birth (intrauterine growth retardation) resulting in low birth weight. Growth deficiency continues after birth, resulting in severe proportionate short stature. Other symptoms and physical features associated with Seckel syndrome include an abnormally small head (microcephaly); varying degrees of intellectual disability; 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 exhibit incurving of the fifth fingers in a bent position (clinodactyly), congenital hip dysplasia, dislocated forearms (radial dislocation), and/or other physical abnormalities. Seckel syndrome inherited as an autosomal recessive genetic trait due to homozygous or compound heterozygous mutation in the ATR gene on chromosome 3q22.1-q24. Other syndromes resembling this disorder are caused by mutations in the RBBP8 gene on chromosome 18q11, mutations in the CENPJ gene on chromosome 13q12; or by mutations in the CEP152 gene on chromosome 15q21. (For more information on this disorder, choose "Seckel" as your search term in the Rare Disease Database.)

Osteodysplastic bird-headed dwarfism, also known as Majewski osteodysplastic primordial dwarfism (MOPD) is an extremely rare inherited disorder characterized by low birth weight, prenatal-onset growth deficiency resulting in severe proportionate short stature with an unusually small head (microcephaly), and characteristic facial features including prominence of the nose, abnormally large eyes, an unusually small jaw (micrognathia) that is recessed (retrognathia), a narrow face, and/or low-set ears. In some cases, affected children may exhibit other abnormalities, such as mild intellectual disability, skeletal deformities, and/or patchy areas of hair loss (alopecia) on the scalp. There are three types of MOPD, designated type I, II, and III, that are distinguished by differences in their symptoms. All are inherited as autosomal recessive genetic traits.

Among children who present with microcephaly and bilateral congenital cataracts with small eyes, one should also consider MICRO syndrome, a rare autosomal recessive disorder characterized by microcephaly, microphthalmia, microcornea, congenital cataracts, optic atrophy, corpus callosum hypoplasia, severe intellectual disability, spastic diplegia, and hypogonadism. This disorder is caused by mutation in the RAB3GAP2 gene on chromosome 1q41, the RAB3GAP1 gene on 2q21.3 or the RAB18 gene on chromosome 10p12.1.

Another possibility is early onset Cockayne syndrome, an autosomal recessive disorder resulting in severe failure to thrive, severe mental retardation, congenital cataracts, loss of adipose tissue, joint contractures, distinctive face with small, deep-set eyes and prominent nasal bridge, kyphosis, and cachectic dwarfism. This disorder is termed Cockayne syndrome type B (CSB) and caused by mutation in the gene encoding the group 6 excision-repair cross-complementing protein (ERCC6) on chromosome 10q11.23. Cockayne syndrome type A (CSA) is caused by mutation in the ERCC8 gene on chromosome 5q11. Among patients with Cockayne syndrome, approximately 80% have mutations in the ERCC6 gene.

Standard Therapies

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 by 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 the abnormalities associated with this disorder. Congenital cataracts with unusually small eyes (microphthalmia) are important findings for the initial diagnosis of Hallermann-Streiff syndrome, but other disorders must be considered as part of the differential diagnosis.

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.

For infants with feeding and respiratory difficulties, early disease management should include monitoring of breathing, consideration of tracheostomy (creation of an opening through the neck into the windpipe into which a tube is inserted, to help maintain an effective airway), and various supportive measures to improve feeding and ensure sufficient intake of nutrients. In addition, early surgical removal of cataracts may be recommended to help preserve vision; however, some investigators indicate that the frequency of spontaneous cataract absorption (see "Symptoms") may be underestimated in those with HSS, suggesting that it may occur in up to 50 percent of untreated patients followed up through five years of age. These physicians may advise waiting for possible spontaneous cataract absorption in selected cases, particularly for patients with significant microphthalmia. Regular close ophthalmology follow-up is strongly recommended to identify and treat other eye abnormalities like nystagmus, ptosis and entropion, which may require surgical intervention to avoid developing a lazy eye (amblyopia) and allow appropriate development of vision. Further investigation is needed regarding the frequency of spontaneous cataract absorption and optimal treatment approaches.

With respect to dental anomalies, it is important to note that the natal/neonatal teeth (teeth present at birth) may be incorrectly diagnosed as supernumerary (extra) teeth and there may be a tendency to extract them. However, apart from their role in mastication (chewing), teeth are also important for maintaining the vertical dimensions of the oral cavity, and the loss of teeth may worsen the glossoptosis (posteriorly location of the tongue) by over closure of the already small lower jaw (micrognathia). Whenever possible every effort should be made to preserve these prematurely erupted deciduous (baby) teeth to facilitate future nutritional intake and prevent unfavorable sequelae, until the existence of successional permanent teeth can be confirmed. Also, because individuals with Hallermann-Streiff syndrome have malformed teeth with abnormal roots they are predisposed to developing severe dental caries making it imperative to ensure good dental hygiene. It may be difficult to perform root canal treatment and other therapies to preserve a tooth with underdeveloped roots, and therefore these patients need appropriate, frequent pediatric dental evaluations.

Recommended disease management may also include surgical reconstruction of certain craniofacial malformations (particularly 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, pediatric anesthesiologists, and other health care providers when making decisions concerning surgery.

For some affected infants and children with heart defects, medical treatment, surgical intervention, and/or other surgical measures may also be recommended. 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.

Investigational Therapies

Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.

For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:

Tollfree: (800) 411-1222
TTY: (866) 411-1010
Email: prpl@cc.nih.gov

For information about clinical trials sponsored by private sources, contact:
www.centerwatch.com

N/A Resources

(Please note that some of these organizations may provide information concerning certain conditions potentially associated with this disorder [e.g., visual handicaps, short stature, craniofacial malformations, etc.].)

NORD Member Organizations:

(To become a member of NORD, an organization must meet established criteria and be approved by the NORD Board of Directors. If you're interested in becoming a member, please contact Susan Olivo, Membership Manager, at solivo@rarediseases.org.)

Other Organizations:

References

JOURNAL ARTICLES
Nucci P, et al. Hallermann-Streiff syndrome with severe bilateral enophthalmos and radiological evidence of silent brain syndrome: a new congenital silent brain syndrome? Clin Ophthalmol. 2011;5:907-11.

Cho WK, et al. Surgical correction of Hallermann-Streiff syndrome: a case report of esotropia, entropion, and blepharoptosis. Korean J Ophthalmol. 2011:142-5.

Hironao N, et al. Reproductive Success in Patients With Hallermann-Streiff Syndrome. Am J Med Genet A. 2011;155A:2311-3.

Robotta P, et al. Hallermann-Streiff syndrome: case report and literature review. Quitessence Int. 2011;42:76-81.

Tuna EB, et al. Craniodentofacial manifestations in Hallermann-Streiff syndrome. Cranio. 2009;27:33-8.

Roulez FM, et al. Corneal opacities in the Hallermann-Streiff syndrome. Ophtahalmic Genet. 2008;29:61-6.

Ahn B, et al. Hallermann-Streiff syndrome: those are not supernumerary teeth. J Pediatr. 2006;148:415.

Sigirci A, et al. Hallermann-Streiff syndrome associated with complete agenesis of the corpus callosum. J Child Neurol. 2005;20:691-3.

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.

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

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

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.

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.

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

Streiff EB. Mandibulofacial dysmorphia with ocular abnormalities.Ophthalmologica. 1950;120(1-2):79-83.

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

INTERNET
Online Mendelian Inheritance in Man (OMIM). The Johns Hopkins University. Hallermann-Streiff Syndrome; HSS. Entry No: 234100. Last Edited December 16, 2011. Available at: http://www.ncbi.nlm.nih.gov/omim/. Accessed April 10, 2012.

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Report last updated: 2012/04/11 00:00:00 GMT+0

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