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

• Burton Skeletal Dysplasia
• Dysostosis Enchondralis Metaepiphysaria, Catel-Hempel type
• Osteochondromuscular Dystrophy

What is Schwartz-Jampel Syndrome? (Definition/Background Information)

• Schwartz-Jampel Syndrome (SJS) is a genetic disorder that affects bone and muscle development. Signs and symptoms may include muscle stiffness and weakness; joint deformities that affect mobility (contractures); short stature; small "fixed" facial features; and eye abnormalities
• Previously, SJS was divided into types 1 and 2. SJS type 2 (also referred to as neonatal SJS) is now considered a distinct, more severe condition called Stuve-Wiedemann syndrome, which is caused by mutations in the LIFR gene
• SJS is subdivided into types 1A and 1B, differentiated by severity and age of onset. Type 1A, considered classic SJS, is the most commonly recognized type. People with type 1A typically develop more mild symptoms later in childhood, while individuals with type 1B have symptoms that are more severe and are apparent immediately after birth
• SJS is caused by mutations in the HSPG2 gene. SJS is thought to be inherited in an autosomal recessive manner; however, some cases reported in the medical literature suggest an autosomal dominant inheritance pattern
• Treatment for type 1A and 1B aims to normalize muscle activity through various methods including massage and stretching, medications such as botulinum toxin (Botox), and surgery

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

Who gets Schwartz-Jampel Syndrome? (Age and Sex Distribution)

• Schwartz-Jampel Syndrome is a rare congenital disorder. 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 Schwartz-Jampel Syndrome? (Predisposing Factors)

• A positive family history may be an important risk factor, since Schwartz-Jampel Syndrome can be inherited
• Currently, no other risk factors have been clearly identified for SJS

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 Schwartz-Jampel Syndrome? (Etiology)

Schwartz-Jampel Syndrome is caused by mutations in the HSPG2 gene.

• The HSPG2 gene provides instructions for making the protein perlecan, which is found in muscle and cartilage. Although function of perlecan is not fully understood, it is thought to play an essential role in many biological activities such as cell signaling and cellular structure
• In SJS, it is suspected that abnormal perlecan function leads to a deficiency of acetylcholinesterase, an enzyme involved in breaking down acetylcholine, a chemical (neurotransmitter) that sends messages between nerves, leading to muscle contraction
• If acetylcholine is not broken down, it can lead to prolonged muscle contraction or stiffening of the muscles (myotonia)

Most cases of SJS are inherited in an autosomal recessive pattern. This means that to have the disorder, a person must have a mutation in both copies of the responsible gene in each cell.

• Individuals with SJS inherit one mutated copy of the gene from each parent. Each parent is referred to as a carrier. Carriers of an autosomal recessive condition typically do not have any signs or symptoms (they are unaffected)
• Rarely, cases of SJS with autosomal dominant inheritance have been reported. This means that having a mutation in only one copy of the responsible gene in each cell is enough to cause features of the condition

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

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.

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 Schwartz-Jampel Syndrome?

The main signs and symptoms of Schwartz-Jampel Syndrome include the following:

• Short stature and other bone abnormalities, such as a short neck, outward-bowed chest (pectus carinatum), curved spine (kyphosis), a hip deformity (coxa valga), and fragile bones (osteoporosis)
• Joint contractures
• Muscle abnormalities, such as an inability to relax muscles (myotonia), increased muscle size (hypertrophy), and muscle weakness
• Characteristic facial features, including a “fixed” expression; a small, puckered mouth; a small lower jaw (micrognathia); and eye abnormalities, such as narrow eye openings (blepharophimosis), involuntary blinking or eyelid spasms (blepharospasm), and skin that covers the inner corner of the eyes (epicanthal folds)

Less common symptoms include:

• A high pitched voice, bilateral carpel tunnel syndrome, and malignant hyperthermia
• One study suggested that as many as 20% of individuals with SJS have an intellectual disability; however, most individuals with SJS have normal intelligence

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

• Abnormality of epiphysis morphology
• Abnormality of the metaphysis
• Elevated aldolase level
• Elevated serum creatine phosphokinase
• EMG abnormality
• Everted lower lip vermilion
• Full cheeks
• Gait disturbance
• Genu valgum
• Hip dysplasia
• Hypertonia
• Intellectual disability
• Joint stiffness
• Low-set, posteriorly rotated ears
• Metatarsus valgus
• Micromelia
• Myotonia
• Narrow mouth
• Pes planus
• Pursed lips
• Skeletal dysplasia
• Trismus
• Visual impairment

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

• Abnormal vertebral ossification
• Abnormality of the eyebrow
• Abnormality of the pharynx
• Blepharophimosis
• Cataract
• Coxa valga
• Coxa vara
• Flat face
• Flexion contracture of toe
• High palate
• High pitched voice
• Hip contracture
• Hyperlordosis
• Hyporeflexia
• Kyphosis
• Mask-like facies
• Micrognathia
• Myopathy
• Myopia
• Osteoporosis
• Overfolded helix
• Pectus carinatum
• Platyspondyly
• Prominent nasal bridge
• Ptosis
• Scoliosis
• Short neck
• Shoulder flexion contracture
• Skeletal muscle hypertrophy
• Spinal rigidity
• Strabismus
• Weak voice
• Wrist flexion contracture

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

• Abnormality of immune system physiology
• Abnormality of the ribs
• Abnormality of the ureter
• Abnormally straight spine
• Anxiety
• Aplasia/Hypoplasia affecting the eye
• Apnea
• Arrhythmia
• Attention deficit hyperactivity disorder
• Blepharospasm
• Cachexia
• Death in infancy
• Decreased testicular size
• Delayed skeletal maturation
• Dental malocclusion
• Distichiasis
• Dysphonia
• Ectopia lentis
• Elbow dislocation
• Feeding difficulties in infancy
• Generalized hirsutism
• Hypertelorism
• Increased bone mineral density
• Increased number of teeth
• Inguinal hernia
• Irritability
• Laryngomalacia
• Long eyelashes in irregular rows
• Long philtrum
• Low anterior hairline
• Malignant hyperthermia
• Microcephaly
• Microcornea
• Myalgia
• Nephrolithiasis
• Odontogenic neoplasm
• Pectus excavatum
• Polyhydramnios
• Prenatal movement abnormality
• Protrusio acetabuli
• Pulmonary arterial hypertension
• Respiratory insufficiency
• Skeletal muscle atrophy
• Sprengel anomaly
• Talipes equinovarus
• Testicular torsion
• Umbilical hernia
• Wormian bones

Other signs and symptoms may include:

• Abnormality of femoral epiphysis
• Anterior bowing of long bones
• Congenital hip dislocation
• Coronal cleft vertebrae
• Joint contracture of the hand
• Kyphoscoliosis
• Low-set ears
• Lumbar hyperlordosis
• Malar flattening
• Metaphyseal widening

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

How is Schwartz-Jampel Syndrome Diagnosed?

Schwartz-Jampel 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 Schwartz-Jampel Syndrome?

The complications of Schwartz-Jampel Syndrome may include:

• Severe physical deformities
• Dysfunction of vital organs

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

How is Schwartz-Jampel Syndrome Treated?

• Treatment of Schwartz-Jampel Syndrome aims to reduce muscle stiffness and cramping and may include massage, muscle warming, and gradual strengthening exercises
• Medications might also be used and may include muscle relaxants and anti-seizure medications, particularly carbamazepine
• Botox might additionally be used to relieve eye symptoms such as blepharospasm
• If Botox is not successful in managing eye symptoms, a variety of surgical techniques have been found to be effective
• When considering surgery as an option, an important consideration is malignant hyperthermia, an associated complication, that can increase the risk of adverse outcomes

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

How can Schwartz-Jampel Syndrome be Prevented?

Currently, Schwartz-Jampel 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 Schwartz-Jampel Syndrome? (Outcomes/Resolutions)

• Most individuals with Schwartz-Jampel Syndrome have a good long-term outlook (prognosis) with a nearly normal life expectancy
• Symptoms may remain stable, or worsen over time, causing increased discomfort
• There is an increased risk of malignant hyperthermia, which may lead to adverse outcomes if not identified prior to surgical intervention or managed correctly during surgery

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

Additional and Relevant Useful Information for Schwartz-Jampel Syndrome:

Schwartz-Jampel Syndrome is also known by the following names:

• Aberfeld Syndrome
• Burton Syndrome
• Catel-Hempel Syndrome
• Chondrodystrophic Myotonia
• Myotonic Myopathy, Dwarfism, Chondrodystrophy, Ocular and Facial Anomalies
• Schwartz Jampel Aberfeld Syndrome (SJA Syndrome)

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

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