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

• Diaphragmatic Defect Limb Deficiency Skull Defect

What is Froster-Huch Syndrome? (Definition/Background Information)

• Froster-Huch Syndrome is characterized by the association of classical diaphragmatic hernia (Bochdalek type) with severe lung hypoplasia, and variable associated malformations
• It has been reported only once in four successive fetuses (two females and two males) born to a non-consanguineous couple
• The spectrum of malformations is wide and includes, besides diaphragmatic hernia and hypoplastic lungs (present in the four fetuses), omphalocele (one case), severe limb hypoplasia (two cases), syndactyly of the toes (two cases), extra spleen (one case), and an ossification defect of the skull (one case)
• Inheritance seems either to be autosomal recessive or due to a gonadal mosaicism in one parent
• Prenatal diagnosis of diaphragmatic hernia and severe lung hypoplasia detected on ultrasonography made the parents opt for termination of the four pregnancies

(Source: Froster-Huch Syndrome; Orphanet, National Institute of Health and Medical Research (INSERM), Paris.)

Who gets Froster-Huch Syndrome? (Age and Sex Distribution)

• Froster-Huch Syndrome is an extremely rare congenital disorder, which was initially described in 4 fetuses of one couple. The condition has subsequently been described in 3 more fetuses
• The symptoms of this condition become apparent in the developing fetus
• Both males and females may be affected
• Worldwide, individuals of all racial and ethnic groups may be affected

What are the Risk Factors for Froster-Huch Syndrome? (Predisposing Factors)

• A positive family history may be an important risk factor, since Froster-Huch 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 Froster-Huch Syndrome? (Etiology)

• Froster-Huch Syndrome may be caused by gene mutation(s) that is inherited in an autosomal recessive manner, or due to gamete or germline mosaicism in one parent
• The exact causative gene mutation for Froster-Huch Syndrome is yet to be identified

Germline or gamete mosaicism is caused by a spontaneous mutation in the germline cells or the germline precursor cells during embryonic development. Such individuals carry genetic mutations only in the sperm or egg, and are clinically normal, showing normal genetic make-up with testing (since somatic cells are generally used for genetic tests). Individuals with mosaicism in the sperm or egg can pass the mutations on to their offspring

Autosomal recessive: Autosomal recessive conditions are traits or disorders that occur when two copies of an abnormal gene have been inherited on a non-sex chromosome. If both parents have an autosomal recessive condition, there is a 100% likelihood of passing on the mutated genes to their children. If, however, only one mutant copy of the gene is inherited, the individual will be a carrier of the condition, but will not be present with any symptoms. Children born to two carriers, have a 25% chance of being homozygous dominant (unaffected), a 50% chance of being heterozygous (carrier), and a 25% chance of being homozygous recessive (affected).

What are the Signs and Symptoms of Froster-Huch Syndrome?

The signs and symptoms of Froster-Huch Syndrome in a developing fetus may include:

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

• Abnormality of femur morphology
• Abnormality of the scapula
• Aplasia/hypoplasia of the fibula
• Aplasia/hypoplasia of the humerus
• Aplasia/hypoplasia of the radius
• Aplasia/hypoplasia of the ulna
• Clinodactyly of the 5th finger
• Congenital diaphragmatic hernia
• Decreased skull ossification
• Finger syndactyly
• Omphalocele
• Pulmonary hypoplasia
• Upper limb asymmetry

Frequently present symptoms in 30-79% of the cases may include abnormality of female internal genitalia.

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

• Abnormality of the diaphragm
• Anteverted nares
• Hypertelorism
• Intestinal malrotation
• Low-set ears
• Syndactyly
• Testicular atrophy
• Toe syndactyly

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

How is Froster-Huch Syndrome Diagnosed?

Froster-Huch Syndrome is diagnosed on the basis of the following information:

• Complete physical examination
• Thorough medical history evaluation
• Assessment of signs and symptoms
• Laboratory tests
• Ultrasonography of a developing fetus

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 Froster-Huch Syndrome?

The complications of Froster-Huch Syndrome may include:

• Profound malformations in the developing fetus
• This may severely affect breathing and feeding after birth

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

How is Froster-Huch Syndrome Treated?

There is no cure for Froster-Huch Syndrome, since it is a genetic condition. If live birth occurs, treatment is usually given to manage the signs and symptoms and any complications that develops.

How can Froster-Huch Syndrome be Prevented?

Currently, Froster-Huch Syndrome may not be preventable, since it is a genetic disorder.

• If there is a family history of the condition, or if one or more fetuses have had 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 Froster-Huch Syndrome? (Outcomes/Resolutions)

The prognosis of Froster-Huch Syndrome is poor, since an affected fetus may show severe abnormalities.

Additional and Relevant Useful Information for Froster-Huch Syndrome:

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

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