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Osteodysplasty, Melnick-Needles type

ORPHA2484
Synonym(s) Melnick-Needles syndrome
Prevalence <1 / 1 000 000
Inheritance X-linked dominant
Age of onset Childhood
ICD-10
  • Q77.8
OMIM
UMLS
  • C0025237
MeSH -
MedDRA
  • 10060908

Summary

Melnick-Needles syndrome (MNS) belongs to the otopalatodigital syndrome spectrum disorder (see this term) and is associated with a short stature, facial dysmorphism, osseous abnormalities involving the majority of the axial and appendicular skeleton resulting in impaired speech and masticatory problems.

To date, less than 70 cases with MNS have been documented. MNS is a disorder essentially limited to females as it is lethal in males. Survivorship in males is possible due to mosaicism.

MNS is a congenital disorder characterized by a short stature, facial dysmorphism (small facies with prominent forehead, full cheeks, retrognathia, marked micrognathia), impaired speech, masticatory problems, and bowing of the arms and lower legs. Eye and ear abnormalities include bilateral exophthalmus, strabismus, blue sclera, conductive deafness and large pinna. Kyphoscoliosis is common. Mitral and tricuspid valve prolapse, bowel malrotation, hydronephrosis, and joint subluxation may be observed. Severe mandibular hypoplasia can cause upper airway restriction, obstructive sleep apnea syndrome and pneumonia and occasionally respiratory failure. Complete atrioventricular canal, prune belly syndrome and omphalocele (see these terms) have been reported in lethally affected males. Intelligence is normal. In females, the syndrome presents with bone dysplasia and facial dysmorphism. Males born to affected mothers show a lethal course of the disease in the embryonic or perinatal period.

MNS is caused by gain of function mutations in the gene FLNA (Xq28) that encodes the actin-binding cytoskeletal protein filamin A. Several lines of evidence suggest that filamin participates in the remodeling of the cytoskeleton during development by integrating cell signaling events with subsequent alterations in cellular shape and motility. MNS is allelic with 4 other skeletal dysplasias (otopalatodigital syndrome type 1 and 2 (OPD1 and OPD2 respectively), terminal osseous dysplasia - pigmentary defects (TOD) and frontometaphyseal dysplasia (FMD) (see these terms).

MNS is inherited in an X-linked dominant manner. Male-to-male transmission has not been reported. The chance of transmitting the mutation in each pregnancy is 50%; males inheriting the mutation will be affected while females who inherit the mutation are less severely affected.

Expert reviewer(s)

  • Pr Stephen ROBERTSON

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Detailed information

Clinical genetics review
  • EN (2013)
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