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

• Melnick-Needles Osteodysplasty
• MNS (Melnick-Needles Syndrome)
• Osteodysplasty of Melnick and Needles

What is Melnick-Needles Syndrome? (Definition/Background Information)

• Melnick-Needles Syndrome (MNS) is a rare disorder involving abnormalities in skeletal development and other health problems. It is a member of a group of related conditions called otopalatodigital spectrum disorders, which typically involve hearing loss caused by malformations in the tiny bones in the ears (ossicles), problems in the development of the roof of the mouth (palate), and skeletal abnormalities involving the fingers and/or toes (digits)
• Melnick-Needles Syndrome is usually the most severe of the otopalatodigital spectrum disorders and males with this condition generally have more severe signs and symptoms than females. In almost all instances, males with Melnick-Needles Syndrome die before or soon after birth
• The signs and symptoms of this condition may include: Short stature, various skeletal abnormalities, characteristic facial features, and abnormalities of the heart and/or kidneys
• This condition is caused by mutations in the FLNA gene, and it is inherited in an X-linked dominant manner
• Although there is no specific treatment or cure for Melnick-Needles syndrome, there may be ways to manage the symptoms. A team of doctors is often needed to figure out the treatment options for each person

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

Who gets Melnick-Needles Syndrome? (Age and Sex Distribution)

• Melnick-Needles Syndrome is an extremely rare congenital disorder with less than 70 cases reported in the medical literature
• The condition can occur in both genders, but is generally more severe in males

What are the Risk Factors for Melnick-Needles Syndrome? (Predisposing Factors)

• A positive family history may be an important risk factor, since Melnick-Needles Syndrome is an inherited condition
• Currently, no other risk factors have been clearly identified for this disorder

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 Melnick-Needles Syndrome? (Etiology)

• Melnick-Needles Syndrome is caused by a mutation in the FLNA gene
• The FLNA gene codes for the filamin A protein, which is crucial for regulation of skeletal development as structural rigidity and mobility of cells
• MNS is inherited in a X-linked dominant manner

X-linked dominant inheritance pattern: In this type of inheritance, the defective gene is carried on the X chromosome. Males have only one X chromosome inherited from their mother and therefore, the defective gene is expressed in them, causing disease. Although females have two X chromosomes, the disease is still manifested in females, albeit less severely, since the FLNA gene mutation on one X chromosome is dominant and masks the effect of the normal gene copy on the other X chromosome.

What are the Signs and Symptoms of Melnick-Needles Syndrome?

The signs and symptoms of Melnick-Needles Syndrome vary in severity between genders, and in type and severity among the affected females too. Individuals with this condition usually have short stature and unusually long fingers and toes. They may additionally have certain skeletal abnormalities including:

• Partial dislocation (subluxation) of certain joints
• Abnormal curvature of the spine (scoliosis)
• Bowed limbs
• Underdeveloped, irregular ribs that can cause problems with breathing
• Other abnormal or absent bones
• Characteristic facial features may include:
• Bulging eyes (proptosis) with prominent brow ridges
• Excess hair growth on the forehead
• Round cheeks
• A very small lower jaw and chin (micrognathia)
• One side of the face that appears noticeably different from the other (facial asymmetry)

Hearing loss is common with this condition and can be either sensorineural or conductive. Intelligence is usually normal.

The signs and symptoms of Melnick-Needles Syndrome may include:

• Anterior concavity of thoracic vertebrae
• Cleft palate
• Coarse hair
• Cone-shaped epiphyses of the phalanges of the hand
• Coxa valga
• Delayed cranial suture closure
• Delayed eruption of teeth
• Failure to thrive
• Flared metaphysis
• Frontal hirsutism
• Gait disturbance
• Genu valgum
• Hip dislocation
• Hoarse voice
• Hydronephrosis 
• Hypertelorism
• Hypoplastic scapulae
• Kyphoscoliosis
• Limited elbow extension
• Long neck
• Macrotia
• Micrognathia
• Misalignment of teeth
• Mitral valve prolapse 
• Motor delay
• Narrow chest
• Obtuse angle of mandible
• Omphalocele
• Osteolytic defects of the phalanges of the hand 
• Pectus excavatum
• Pes planus
• Prominent supraorbital ridges
• Proptosis
• Pulmonary arterial hypertension
• Recurrent otitis media
• Recurrent respiratory infections
• Short clavicles
• Short distal phalanx of finger
• Short humerus
• Small face
• Stillbirth
• Strabismus
• Talipes equinovarus
• Tibial bowing
• Tricuspid valve prolapse
• Ureteral stenosis

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

How is Melnick-Needles Syndrome Diagnosed?

Melnick-Needles 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
• Molecular genetic testing to check for or confirm causative FLNA gene mutation(s)

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 Melnick-Needles Syndrome?

The complications of Melnick-Needles Syndrome may include:

• Scarring and fibrosis in airway and lungs due to recurrent respiratory infections
• Severe pain due to dislocation of joints
• Problems with chewing food
• Speech impairment
• Abnormal heart function due to structural defects in the organ
• Reduced quality of life

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

How is Melnick-Needles Syndrome Treated?

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

How can Melnick-Needles Syndrome be Prevented?

Currently, Melnick-Needles 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 Melnick-Needles Syndrome? (Outcomes/Resolutions)

• The prognosis of Melnick-Needles Syndrome is poor in males, since the manifestation of symptoms is severe. A majority of male children succumb to MNS before or soon after birth
• Some males do survive due to mosaicism, in which different cells of the individual may have different chromosomal arrangements. In essence, not all cells will have the lethal FLNA gene carrying X chromosome in such individuals
• Typically, the prognosis may be assessed on a case-by-case basis

Additional and Relevant Useful Information for Melnick-Needles Syndrome:

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

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