What are the other Names for this Condition? (Also known as/Synonyms)

• Holoprosencephaly-Radial Heart Renal Anomalies Syndrome

What is Steinfeld Syndrome? (Definition/Background Information)

• Steinfeld Syndrome, or Holoprosencephaly-Radial Heart Renal Anomalies Syndrome is characterised by holoprosencephaly, predominantly radial limb deficiency (absent thumbs, phocomelia), heart defects, kidney malformations and absence of gallbladder
• Variable manifestations include vertebral anomalies, cleft lip/palate, microphthalmia, absent nose, dysplastic ears, hearing loss, colobomas of the iris and retina and/or bifid uvula
• Inheritance is likely to be autosomal dominant with variable expressivity

(Source: Holoprosencephaly-radial heart renal anomalies syndrome; Orphanet, National Institute of Health and Medical Research (INSERM), Paris.)

Who gets Steinfeld Syndrome? (Age and Sex Distribution)

• Steinfeld Syndrome is an extremely rare congenital disorder that has been only described in a couple of families (totaling about 7 members) 
• The presentation of symptoms may occur at birth
• Both males and females may be affected
• Worldwide, individuals of all racial and ethnic groups may be affected

What are the Risk Factors for Steinfeld Syndrome? (Predisposing Factors)

• A positive family history may be an important risk factor, since Steinfeld Syndrome can be inherited
• Currently, no other risk factors have been clearly identified for the syndrome

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Steinfeld Syndrome? (Etiology)

• Currently, the exact cause of development of Steinfeld Syndrome is not known
• It is believed to be inherited in an autosomal dominant manner with variable expressivity

Autosomal dominant: Autosomal dominant conditions are traits or disorders that are present when only one copy of the mutation is inherited on a non-sex chromosome. In these types of conditions, the individual has one normal copy and one mutant copy of the gene. The abnormal gene dominates, masking the effects of the correctly function gene. If an individual has an autosomal dominant condition, the chance of passing the abnormal gene on to their offspring is 50%. Children, who do not inherit the abnormal gene, will not develop the condition or pass it on to their offspring.

Steinfeld Syndrome shows variable expressivity, indicating that factors other than inherited genes play a role in the manifestation of disease symptoms. These factors may include environment and lifestyle choices of individuals with the defective gene. Autosomal dominant inheritance with variable expressivity leads to significant variations in the signs and symptoms of the affected individuals, in both type and severity.

What are the Signs and Symptoms of Steinfeld Syndrome?

The signs and symptoms of Steinfeld Syndrome may vary among affected individuals in type and severity. Based on the frequency of symptoms observed, the following information may be noted:

Very frequently present symptoms in 80-99% of the cases:

• Aplasia of the nose
• Atresia of the external auditory canal
• Holoprosencephaly
• Microcephaly

Frequently present symptoms in 30-79% of the cases:

• Aplasia/hypoplasia of the thumb
• Hypoplasia of the radius
• Hypoplasia of the ulna
• Microphthalmia
• Vertebral segmentation defect

Occasionally present symptoms in 5-29% of the cases:

• Abnormal localization of kidney
• Abnormality of neuronal migration
• Abnormality of the humerus
• Cyclopia
• Foot polydactyly
• Hearing impairment
• Hypotelorism
• Iridoretinal coloboma
• Median cleft lip
• Missing ribs
• Omphalocele
• Overriding aorta
• Phocomelia
• Renal hypoplasia/aplasia
• Tetralogy of Fallot

In addition to the above, the following signs and symptoms may be present in some affected individuals:

• Abnormal heart morphology
• Abnormal vertebral morphology
• Abnormality of the pinna
• Abnormality of the vertebral column
• Bifid uvula
• Median cleft lip and palate
• Unilateral renal dysplasia

(Source: Steinfeld Syndrome; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

How is Steinfeld Syndrome Diagnosed?

Steinfeld Syndrome is diagnosed on the basis of the following information:

• Complete physical examination
• Thorough medical history evaluation
• Assessment of signs and symptoms
• Laboratory tests
• Imaging studies
• Biopsy studies, if necessary

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Steinfeld Syndrome?

The complications of Steinfeld Syndrome may include:

• Severe kidney malfunction leading to kidney failure
• Cardiac arrest
• Absence of gallbladder

Complications may occur with or without treatment, and in some cases, due to treatment also.

How is Steinfeld Syndrome Treated?

There is no cure for Steinfeld Syndrome, since it is a genetic condition. The treatment is usually given to manage the signs and symptoms and any complications that develops.

How can Steinfeld Syndrome be Prevented?

Steinfeld Syndrome may not be preventable, since it is a genetic disorder.

• Genetic testing of the expecting parents (and related family members) and prenatal diagnosis (molecular testing of the fetus during pregnancy) may help in understanding the risks better during pregnancy
• If there is a family history of the condition, then genetic counseling will help assess risks, before planning for a child
• Active research is currently being performed to explore the possibilities for treatment and prevention of inherited and acquired genetic disorders
• Regular medical screening at periodic intervals with tests and physical examinations are recommended

What is the Prognosis of Steinfeld Syndrome? (Outcomes/Resolutions)

• The prognosis of Steinfeld Syndrome is dependent upon the severity of the signs and symptoms and associated complications, if any
• Individuals with mild conditions have better prognosis than those with severe symptoms and complications
• Typically, the prognosis may be assessed on a case-by-case basis

Additional and Relevant Useful Information for Steinfeld Syndrome:

The following DoveMed website link is a useful resource for additional information:

http://www.dovemed.com/diseases-conditions/rare-disorders/