Melnick-Needles syndrome 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.

• 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)
• Misaligned teeth
• 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.

FLNA gene. When the FLNA gene is working correctly, it provides instructions for producing a protein called filamin A, which is needed to help other proteins and to give structure to cells and allow them to change shape and move. When the FLNA gene has a mutation that causes Melnick-Needles syndrome, the mutation instructs the cell to enhance the activity of the filamin A protein or give the protein a new function. Researchers believe that the mutations may change the way the filamin A protein helps regulate processes involved in skeletal development, but it is not known how changes in the protein relate to the specific signs and symptoms of Melnick-Needles syndrome.

Because males have only one X chromosome (and one Y chromosome) and females have two X chromosomes, X-linked dominant conditions affect males and females differently. Both males and females can have an X-linked dominant condition. However, because males don't have a second, working copy of the gene (as females do), they usually have more severe disease than females.

If a father has the mutated X-linked gene:

• all of his daughters will inherit the mutated gene (they will all receive his X chromosome)
• none of his sons will inherit the mutated gene (they only inherit his Y chromosome)

If a mother has the mutated X-linked gene, each of her children (both male and female) has a 50% chance to inherit the mutated gene.

Rather than being inherited from a parent, the condition may also be caused by a new mutation that occurs for the first time in an affected person (a de novo mutation).

Melnick-Needles syndrome and other forms of otopalatodigital (OPD) spectrum disorders are diagnosed based on a combination of clinical examination, radiologic studies (such as X-rays), family history consistent with X-linked inheritance, and genetic testing.