Dyggve-Melchior-Clausen Syndrome

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

• DMC Syndrome
• Dyggve-Melchior-Clausen Disease

What is Dyggve-Melchior-Clausen Syndrome? (Definition/Background Information)

• Dyggve-Melchior-Clausen (DMC) Syndrome is a rare, progressive genetic condition characterized by abnormal skeletal development, microcephaly, and intellectual disability. Only about 100 cases have been reported to date
• Skeletal abnormalities may include a barrel-shaped chest with a short truck, partial dislocation of the hips, knock knees, bowlegs, and decreased joint mobility
• A small number of affected individuals experience instability in the upper neck vertebrae that can lead to spinal cord compression, weakness and paralysis. Normally, there is growth deficiency resulting in short stature
• DMC Syndrome is caused by mutations in the DYM gene and is inherited in an autosomal recessive manner
• Some researchers have described an X-linked pattern of inheritance, which has not been confirmed to date

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

Who gets Dyggve-Melchior-Clausen Syndrome? (Age and Sex Distribution)

• Dyggve-Melchior-Clausen 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 Dyggve-Melchior-Clausen Syndrome? (Predisposing Factors)

• A positive family history may be an important risk factor, since Dyggve-Melchior-Clausen Syndrome is an inherited condition
• Currently, no risk factors have been clearly identified for DMC 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 Dyggve-Melchior-Clausen Syndrome? (Etiology)

• DMC Syndrome is caused by mutations in the DYM gene and is inherited in an autosomal recessive manner
• Some researchers have described an X-linked pattern of inheritance, which has not been confirmed to date

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

What are the Signs and Symptoms of Dyggve-Melchior-Clausen Syndrome?

Newborns affected by Dyggve-Melchior-Clausen Syndrome may be small at birth, but otherwise appear normal. Skeletal findings are often recognized first between 1 and 18 months. With age, other characteristics begin to develop. Chest deformities, feeding difficulties, and developmental delay usually occur before 18 months. Disproportionate short stature usually occurs after 18 months. Additional features may include a long skull, distinctive facial appearance, a protruding jaw, microcephaly, and claw-like hands. Intellectual disability occurs in most cases, ranging from moderate to severe.

Affected individuals can also develop a protruding breastbone; spinal abnormalities; abnormal bones in the hands, fingers, toes, wrists, and long bones of the arms and legs; and joint contractures, especially of the elbows and hips. Secondary problems resulting from the skeletal abnormalities may include spinal compression, dislocated hips, and restricted joint mobility. These problems may in turn cause a waddling gait.

The signs and symptoms of Dyggve-Melchior-Clausen Syndrome may include:

• Abnormality of the nervous system
• Avascular necrosis of the capital femoral epiphysis
• Barrel-shaped chest
• Beaking of vertebral bodies
• Brachycephaly
• Broad foot
• Camptodactyly
• Carpal bone hypoplasia
• Coarse facial features
• Cone-shaped epiphyses of the phalanges of the hand
• Coxa vara
• Deformed sella turcica
• Disproportionate short-trunk short stature
• Distal ulnar hypoplasia
• Enlargement of the costochondral junction
• Flat acetabular roof
• Flat glenoid fossa
• Genu valgum
• Hallux valgus
• Hypoplastic facial bones
• Hypoplastic iliac wing
• Hypoplastic ischia
• Hypoplastic pelvis
• Hypoplastic sacrum
• Hypoplastic scapulae
• Iliac crest serration
• Irregular iliac crest
• Lumbar hyperlordosis
• Multicentric ossification of proximal femoral epiphyses
• Multicentric ossification of proximal humeral epiphyses
• Narrow greater sacrosciatic notches
• Platyspondyly
• Prominent sternum
• Rhizomelia
• Scoliosis
• Severe global developmental delay
• Shield chest
• Short femoral neck
• Short metacarpal
• Short metatarsal
• Short neck
• Spondyloepimetaphyseal dysplasia
• Thoracic kyphosis
• Waddling gait
• Wide pubic symphysis

Based on the frequency of symptoms observed, the following information may be noted:

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

• Abnormality of epiphysis morphology
• Abnormality of the ilium
• Abnormality of the metaphysis
• Hip dislocation
• Intellectual disability
• Micromelia
• Pectus carinatum
• Short thorax
• Skeletal dysplasia

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

• Abnormality of the wrist
• Hyperlordosis
• Hypoplasia of the odontoid process
• Joint stiffness 
• Kyphosis
• Microcephaly 
• Neurological speech impairment 
• Postnatal growth retardation 
• Sloping forehead 
• Spinal canal stenosis

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

• Attention deficit hyperactivity disorder
• Autism  
• Shoulder dislocation

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

How is Dyggve-Melchior-Clausen Syndrome Diagnosed?

• Dyggve-Melchior-Clausen Syndrome may be suspected following a thorough clinical evaluation, a detailed patient history, and identification of characteristic findings (e.g., barrel chest, and disproportionate short stature)
• Radiographs may confirm specific skeletal abnormalities and findings consistent with DMC syndrome
• Genetic testing can also confirm a diagnosis

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

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 Dyggve-Melchior-Clausen Syndrome?

The complications of Dyggve-Melchior-Clausen Syndrome may include:

• Severe bony abnormalities
• Neurological impairment
• Reduced quality of life

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

How is Dyggve-Melchior-Clausen Syndrome Treated?

Treatment of individuals with Dyggve-Melchior-Clausen Syndrome depends on the affected person's symptoms and is usually supportive. There is no cure for this condition.

• Treatments might include spinal fusion of the segments of the spinal column at the top of the spine or other means of vertebral stabilization
• Additional surgical techniques may be used to correct various skeletal abnormalities such as dislocation of the shoulder and hip joints
• In some cases, hip replacement is required. Children with DMC Syndrome may benefit from early intervention and special educational programs

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

How can Dyggve-Melchior-Clausen Syndrome be Prevented?

Currently, Dyggve-Melchior-Clausen 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 Dyggve-Melchior-Clausen Syndrome? (Outcomes/Resolutions) 

Dyggve-Melchior-Clausen Syndrome is a progressive condition, meaning that signs and symptoms worsen over time.

• The orthopedic complications usually progress, which can include lumbar lordosis, thoracic kyphosis, scoliosis, dislocation in the hip joints, deformed knees, and spinal cord compression
• Adult height is severely reduced with height ranging from 82 cm to 128 cm (32 in to 50 in)
• Neurological complications may include hyperactivity, autistic-like behavior, lack of speech, and mild to severe intellectual disability

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

Additional and Relevant Useful Information for Dyggve-Melchior-Clausen Syndrome:

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

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