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Melnick-Needles syndrome(MNS)

MedGen UID:
6292
Concept ID:
C0025237
Disease or Syndrome
Synonyms: Melnick-Needles osteodysplasty; MNS; Osteodysplasty of Melnick and Needles
SNOMED CT: Osteodysplasty (13449007); Melnick-Needles syndrome (13449007)
Modes of inheritance:
X-linked dominant inheritance
MedGen UID:
376232
Concept ID:
C1847879
Finding
Source: Orphanet
A mode of inheritance that is observed for dominant traits related to a gene encoded on the X chromosome. In the context of medical genetics, X-linked dominant disorders tend to manifest very severely in affected males. The severity of manifestation in females may depend on the degree of skewed X inactivation.
 
Gene (location): FLNA (Xq28)
 
Monarch Initiative: MONDO:0010650
OMIM®: 309350
Orphanet: ORPHA2484

Disease characteristics

Excerpted from the GeneReview: X-Linked Otopalatodigital Spectrum Disorders
The X-linked otopalatodigital (X-OPD) spectrum disorders, characterized primarily by skeletal dysplasia, include the following: Otopalatodigital syndrome type 1 (OPD1). Otopalatodigital syndrome type 2 (OPD2). Frontometaphyseal dysplasia type 1 (FMD1). Melnick-Needles syndrome (MNS). Terminal osseous dysplasia with pigmentary skin defects (TODPD). In OPD1, most manifestations are present at birth; females can present with severity similar to affected males, although some have only mild manifestations. In OPD2, females are less severely affected than related affected males. Most males with OPD2 die during the first year of life, usually from thoracic hypoplasia resulting in pulmonary insufficiency. Males who live beyond the first year of life are usually developmentally delayed and require respiratory support and assistance with feeding. In FMD1, females are less severely affected than related affected males. Males do not experience a progressive skeletal dysplasia but may have joint contractures and hand and foot malformations. Progressive scoliosis is observed in both affected males and females. In MNS, wide phenotypic variability is observed; some individuals are diagnosed in adulthood, while others require respiratory support and have reduced longevity. MNS in males results in perinatal lethality in all recorded cases. TODPD, seen only in females, is characterized by a skeletal dysplasia that is most prominent in the digits, pigmentary defects of the skin, and recurrent digital fibromata. [from GeneReviews]
Authors:
Stephen Robertson   view full author information

Additional descriptions

From OMIM
Melnick-Needles syndrome is 1 of 4 otopalatodigital syndromes caused by mutations in the FLNA gene. These disorders, including frontometaphyseal dysplasia (FMD; 305620), otopalatodigital syndrome-1 (OPD1; 311300), and otopalatodigital syndrome-2 (OPD2; 304120), constitute a phenotypic spectrum. At the mild end of the spectrum, males with OPD1 have cleft palate and mild skeletal anomalies with conductive deafness caused by ossicular anomalies. FMD is characterized by a generalized skeletal dysplasia, deafness and urogenital defects. Males with OPD2 have disabling skeletal anomalies in addition to variable malformations in the hindbrain, heart, intestines, and kidneys that frequently lead to perinatal death. The most severe phenotype, MNS, is characterized by a skeletal dysplasia in the heterozygote. Affected males exhibit severe malformations similar to those observed in individuals with OPD2, resulting in prenatal lethality or death in the first few months of life (review by Robertson, 2005). Verloes et al. (2000) suggested that these disorders constitute a single entity, which they called 'fronto-otopalatodigital osteodysplasia.'  http://www.omim.org/entry/309350
From MedlinePlus Genetics
Melnick-Needles syndrome is a 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 also includes otopalatodigital syndrome type 1, otopalatodigital syndrome type 2, frontometaphyseal dysplasia, and terminal osseous dysplasia. In general, these disorders 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. People with this condition are usually of short stature, have an abnormal curvature of the spine (scoliosis), partial dislocation (subluxation) of certain joints, and unusually long fingers and toes. They may have bowed limbs; underdeveloped, irregular ribs that can cause problems with breathing; and other abnormal or absent bones.

Characteristic facial features may include bulging eyes with prominent brow ridges, excess hair growth on the forehead, round cheeks, a very small lower jaw and chin (micrognathia), and misaligned teeth. One side of the face may appear noticeably different from the other (facial asymmetry). Some individuals with this disorder have hearing loss.

In addition to skeletal abnormalities, individuals with Melnick-Needles syndrome may have obstruction of the ducts between the kidneys and bladder (ureters) or heart defects.

Males with Melnick-Needles syndrome generally have much more severe signs and symptoms than do females, and in almost all cases die before or soon after birth.  https://medlineplus.gov/genetics/condition/melnick-needles-syndrome

Clinical features

From HPO
Hydronephrosis
MedGen UID:
42531
Concept ID:
C0020295
Disease or Syndrome
Severe distention of the kidney with dilation of the renal pelvis and calices.
Ureteral stenosis
MedGen UID:
105481
Concept ID:
C0521618
Anatomical Abnormality
The presence of a stenotic, i.e., constricted ureter.
Clubfoot
MedGen UID:
3130
Concept ID:
C0009081
Congenital Abnormality
Clubfoot is a congenital limb deformity defined as fixation of the foot in cavus, adductus, varus, and equinus (i.e., inclined inwards, axially rotated outwards, and pointing downwards) with concomitant soft tissue abnormalities (Cardy et al., 2007). Clubfoot may occur in isolation or as part of a syndrome (e.g., diastrophic dysplasia, 222600). Clubfoot has been reported with deficiency of long bones and mirror-image polydactyly (Gurnett et al., 2008; Klopocki et al., 2012).
Pes planus
MedGen UID:
42034
Concept ID:
C0016202
Anatomical Abnormality
A foot where the longitudinal arch of the foot is in contact with the ground or floor when the individual is standing; or, in a patient lying supine, a foot where the arch is in contact with the surface of a flat board pressed against the sole of the foot by the examiner with a pressure similar to that expected from weight bearing; or, the height of the arch is reduced.
Coxa valga
MedGen UID:
116080
Concept ID:
C0239137
Finding
Coxa valga is a deformity of the hip in which the angle between the femoral shaft and the femoral neck is increased compared to age-adjusted values (about 150 degrees in newborns gradually reducing to 120-130 degrees in adults).
Genu valgum
MedGen UID:
154364
Concept ID:
C0576093
Anatomical Abnormality
The legs angle inward, such that the knees are close together and the ankles far apart.
Acroosteolysis
MedGen UID:
183017
Concept ID:
C0917990
Disease or Syndrome
Dissolution or degeneration of bone tissue of the phalanges of the hand.
Short humerus
MedGen UID:
316907
Concept ID:
C1832117
Congenital Abnormality
Underdevelopment of the humerus.
Tibial bowing
MedGen UID:
332360
Concept ID:
C1837081
Finding
A bending or abnormal curvature of the tibia.
Short distal phalanx of finger
MedGen UID:
326590
Concept ID:
C1839829
Finding
Short distance from the end of the finger to the most distal interphalangeal crease or the distal interphalangeal joint flexion point. That is, hypoplasia of one or more of the distal phalanx of finger.
Limited elbow extension
MedGen UID:
401158
Concept ID:
C1867103
Finding
Limited ability to straighten the arm at the elbow joint.
Mitral valve prolapse
MedGen UID:
7671
Concept ID:
C0026267
Disease or Syndrome
One or both of the leaflets (cusps) of the mitral valve bulges back into the left atrium upon contraction of the left ventricle.
Tricuspid valve prolapse
MedGen UID:
11912
Concept ID:
C0040962
Disease or Syndrome
One or more of the leaflets (cusps) of the tricuspid valve bulges back into the right atrium upon contraction of the right ventricle.
Pulmonary arterial hypertension
MedGen UID:
425404
Concept ID:
C2973725
Disease or Syndrome
Pulmonary hypertension is defined mean pulmonary artery pressure of 25mmHg or more and pulmonary capillary wedge pressure of 15mmHg or less when measured by right heart catheterisation at rest and in a supine position.
Failure to thrive
MedGen UID:
746019
Concept ID:
C2315100
Disease or Syndrome
Failure to thrive (FTT) refers to a child whose physical growth is substantially below the norm.
Macrotia
MedGen UID:
488785
Concept ID:
C0152421
Congenital Abnormality
Median longitudinal ear length greater than two standard deviations above the mean and median ear width greater than two standard deviations above the mean (objective); or, apparent increase in length and width of the pinna (subjective).
Gait disturbance
MedGen UID:
107895
Concept ID:
C0575081
Finding
The term gait disturbance can refer to any disruption of the ability to walk. In general, this can refer to neurological diseases but also fractures or other sources of pain that is triggered upon walking. However, in the current context gait disturbance refers to difficulty walking on the basis of a neurological or muscular disease.
Motor delay
MedGen UID:
381392
Concept ID:
C1854301
Finding
A type of Developmental delay characterized by a delay in acquiring motor skills.
Hip dislocation
MedGen UID:
42455
Concept ID:
C0019554
Injury or Poisoning
Displacement of the femur from its normal location in the hip joint.
Micrognathia
MedGen UID:
44428
Concept ID:
C0025990
Congenital Abnormality
Developmental hypoplasia of the mandible.
Delayed cranial suture closure
MedGen UID:
75805
Concept ID:
C0277828
Finding
Infants normally have two fontanels at birth, the diamond-shaped anterior fontanelle at the junction of the coronal and sagittal sutures, and the posterior fontanelle at the intersection of the occipital and parietal bones. The posterior fontanelle usually closes by the 8th week of life, and the anterior fontanel closes by the 18th month of life on average. This term applies if there is delay of closure of the fontanelles beyond the normal age.
Narrow chest
MedGen UID:
96528
Concept ID:
C0426790
Finding
Reduced width of the chest from side to side, associated with a reduced distance from the sternal notch to the tip of the shoulder.
Short clavicles
MedGen UID:
96529
Concept ID:
C0426799
Congenital Abnormality
Reduced length of the clavicles.
Kyphoscoliosis
MedGen UID:
154361
Concept ID:
C0575158
Anatomical Abnormality
An abnormal curvature of the spine in both a coronal (lateral) and sagittal (back-to-front) plane.
Congenital omphalocele
MedGen UID:
162756
Concept ID:
C0795690
Congenital Abnormality
An omphalocele is an abdominal wall defect limited to an open umbilical ring, and is characterized by the herniation of membrane-covered internal organs into the open base of the umbilical cord. Omphalocele is distinguished from gastroschisis (230750), in which the abdominal wall defect is located laterally to a normally closed umbilical ring with herniation of organs that are uncovered by membranes (summary by Bugge, 2010). On the basis of clinical manifestations, epidemiologic characteristics, and the presence of additional malformations, Yang et al. (1992) concluded that omphalocele and gastroschisis are casually and pathogenetically distinct abdominal wall defects. Omphalocele can be a feature of genetic disorders, such as Beckwith-Wiedemann syndrome (130650) and the Shprintzen-Goldberg syndrome (182210).
Anterior concavity of thoracic vertebrae
MedGen UID:
326972
Concept ID:
C1839822
Finding
Hypoplastic scapulae
MedGen UID:
337579
Concept ID:
C1846434
Finding
Underdeveloped scapula.
Flared metaphysis
MedGen UID:
337976
Concept ID:
C1850135
Finding
The presence of a splayed (i.e.,flared) metaphyseal segment of one or more long bones.
Cone-shaped epiphyses of the phalanges of the hand
MedGen UID:
347156
Concept ID:
C1859480
Finding
A cone-shaped appearance of the epiphyses of the fingers of the hand, producing a 'ball-in-a-socket' appearance. The related entity 'angel-shaped' epiphysis refers to a pronounced cone-shaped epiphysis in combination with a pseudoepiphysis at the distal end of a phalanx.
Pectus excavatum
MedGen UID:
781174
Concept ID:
C2051831
Finding
A defect of the chest wall characterized by a depression of the sternum, giving the chest ("pectus") a caved-in ("excavatum") appearance.
Obtuse angle of mandible
MedGen UID:
871603
Concept ID:
C4038738
Finding
Abnormally flat (obtuse) angle of the mandible. The angle of the mandibular, located at the junction between the body and the ramus of the mandible, is normally close to being a right angle. This terms describes an abnormal increase of this angle such that the mandible appears flatter than normal.
Recurrent respiratory infections
MedGen UID:
812812
Concept ID:
C3806482
Finding
An increased susceptibility to respiratory infections as manifested by a history of recurrent respiratory infections.
Recurrent otitis media
MedGen UID:
155436
Concept ID:
C0747085
Disease or Syndrome
Increased susceptibility to otitis media, as manifested by recurrent episodes of otitis media.
Hoarse voice
MedGen UID:
5602
Concept ID:
C0019825
Sign or Symptom
Hoarseness refers to a change in the pitch or quality of the voice, with the voice sounding weak, very breathy, scratchy, or husky.
Delayed eruption of teeth
MedGen UID:
68678
Concept ID:
C0239174
Finding
Delayed tooth eruption, which can be defined as tooth eruption more than 2 SD beyond the mean eruption age.
Long neck
MedGen UID:
333409
Concept ID:
C1839816
Finding
Increased inferior-superior length of the neck.
Prominent supraorbital ridges
MedGen UID:
333982
Concept ID:
C1842060
Finding
Greater than average forward and/or lateral protrusion of the supraorbital portion of the frontal bones.
Tooth malposition
MedGen UID:
377692
Concept ID:
C1852504
Finding
Abnormal alignment, positioning, or spacing of the teeth, i.e., misaligned teeth.
Small face
MedGen UID:
343376
Concept ID:
C1855538
Finding
A face that is short and narrow.
Cleft palate
MedGen UID:
756015
Concept ID:
C2981150
Congenital Abnormality
Cleft palate is a developmental defect of the palate resulting from a failure of fusion of the palatine processes and manifesting as a separation of the roof of the mouth (soft and hard palate).
Coarse hair
MedGen UID:
124454
Concept ID:
C0277959
Finding
Hair shafts are rough in texture.
Frontal hirsutism
MedGen UID:
333413
Concept ID:
C1839830
Finding
Excessive amount of hair growth on forehead.
Proptosis
MedGen UID:
41917
Concept ID:
C0015300
Disease or Syndrome
An eye that is protruding anterior to the plane of the face to a greater extent than is typical.
Hypertelorism
MedGen UID:
9373
Concept ID:
C0020534
Finding
Although hypertelorism means an excessive distance between any paired organs (e.g., the nipples), the use of the word has come to be confined to ocular hypertelorism. Hypertelorism occurs as an isolated feature and is also a feature of many syndromes, e.g., Opitz G syndrome (see 300000), Greig cephalopolysyndactyly (175700), and Noonan syndrome (163950) (summary by Cohen et al., 1995).
Strabismus
MedGen UID:
21337
Concept ID:
C0038379
Disease or Syndrome
A misalignment of the eyes so that the visual axes deviate from bifoveal fixation. The classification of strabismus may be based on a number of features including the relative position of the eyes, whether the deviation is latent or manifest, intermittent or constant, concomitant or otherwise and according to the age of onset and the relevance of any associated refractive error.

Term Hierarchy

Follow this link to review classifications for Melnick-Needles syndrome in Orphanet.

Professional guidelines

PubMed

Leiva-Gea A, Martos Lirio MF, Barreda Bonis AC, Marín Del Barrio S, Heath KE, Marín Reina P, Guillén-Navarro E, Santos Simarro F, Riaño Galán I, Yeste Fernández D, Leiva-Gea I
An Pediatr (Engl Ed) 2022 Dec;97(6):423.e1-423.e11. Epub 2022 Nov 5 doi: 10.1016/j.anpede.2022.10.004. PMID: 36347803
Sawamoto K, Álvarez González JV, Piechnik M, Otero FJ, Couce ML, Suzuki Y, Tomatsu S
Int J Mol Sci 2020 Feb 23;21(4) doi: 10.3390/ijms21041517. PMID: 32102177Free PMC Article
Rossi V, Lee B, Marom R
Curr Opin Pediatr 2019 Dec;31(6):708-715. doi: 10.1097/MOP.0000000000000813. PMID: 31693577Free PMC Article

Recent clinical studies

Etiology

Lykissas MG, Crawford AH, Shufflebarger HL, Gaines S, Permal V
J Pediatr Orthop 2013 Mar;33(2):170-4. doi: 10.1097/BPO.0b013e3182776edb. PMID: 23389572
Jung S, Wermker K, Joos U, Kleinheinz J
Int J Oral Maxillofac Surg 2012 Mar;41(3):309-12. Epub 2011 Oct 19 doi: 10.1016/j.ijom.2011.08.007. PMID: 22014680
Molina FM, Morales C, Taylor JA
J Craniofac Surg 2008 Jan;19(1):277-9. doi: 10.1097/SCS.0b013e3181577aab. PMID: 18216701
Dereymaeker AM, Christens J, Eeckels R, Heremans G, Fryns JP
Helv Paediatr Acta 1986 Oct;41(4):339-51. PMID: 3793511
ter Haar B, Hamel B, Hendriks J, de Jager J
Am J Med Genet 1982 Dec;13(4):469-77. doi: 10.1002/ajmg.1320130418. PMID: 7158646

Diagnosis

Riccio MP, D'Andrea G, Sarnataro E, Marino M, Bravaccio C, Albert U
J Med Case Rep 2021 Oct 11;15(1):495. doi: 10.1186/s13256-021-03064-1. PMID: 34629090Free PMC Article
Oh CH, Lee CH, Kim SY, Lee SY, Jun HH, Lee S
BMC Pediatr 2020 Aug 19;20(1):391. doi: 10.1186/s12887-020-02288-2. PMID: 32814550Free PMC Article
Kothari V, Anand R, Chandra J, Garg DP
Indian Pediatr 1995 Apr;32(4):471-5. PMID: 8635812
Hamel BC, Draaisma JM, Pinckers AJ, Boetes C, Hoppe RL, Ropers HH, Brunner HG
Am J Med Genet 1995 Apr 10;56(3):312-6. doi: 10.1002/ajmg.1320560320. PMID: 7778598
Perry LD, Edwards WC, Bramson RT
J Pediatr Ophthalmol Strabismus 1978 Jul-Aug;15(4):226-30. doi: 10.3928/0191-3913-19780701-09. PMID: 105122

Prognosis

Luo X, Yang Z, Zeng J, Chen J, Chen N, Jiang X, Wei Q, Yi P, Xu J
Mol Genet Genomic Med 2023 May;11(5):e2145. Epub 2023 Feb 3 doi: 10.1002/mgg3.2145. PMID: 36734119Free PMC Article
Lykissas MG, Crawford AH, Shufflebarger HL, Gaines S, Permal V
J Pediatr Orthop 2013 Mar;33(2):170-4. doi: 10.1097/BPO.0b013e3182776edb. PMID: 23389572
Jung S, Wermker K, Joos U, Kleinheinz J
Int J Oral Maxillofac Surg 2012 Mar;41(3):309-12. Epub 2011 Oct 19 doi: 10.1016/j.ijom.2011.08.007. PMID: 22014680
Hamel BC, Draaisma JM, Pinckers AJ, Boetes C, Hoppe RL, Ropers HH, Brunner HG
Am J Med Genet 1995 Apr 10;56(3):312-6. doi: 10.1002/ajmg.1320560320. PMID: 7778598
Dereymaeker AM, Christens J, Eeckels R, Heremans G, Fryns JP
Helv Paediatr Acta 1986 Oct;41(4):339-51. PMID: 3793511

Clinical prediction guides

Luo X, Yang Z, Zeng J, Chen J, Chen N, Jiang X, Wei Q, Yi P, Xu J
Mol Genet Genomic Med 2023 May;11(5):e2145. Epub 2023 Feb 3 doi: 10.1002/mgg3.2145. PMID: 36734119Free PMC Article
Mercer CL, Andreoletti G, Carroll A, Salmon AP, Temple IK, Ennis S
Circ Cardiovasc Genet 2017 Dec;10(6) doi: 10.1161/CIRCGENETICS.116.001683. PMID: 29237676
Femiano P, Castaldo V, Iossa C, Pascarella F
Minerva Pediatr 2005 Dec;57(6):419-22. PMID: 16402013
Unal VS, Derici O, Oken F, Turan S, Girgin O
J Pediatr Orthop B 2004 Mar;13(2):88-91. doi: 10.1097/00009957-200403000-00005. PMID: 15076585
Robertson S, Gunn T, Allen B, Chapman C, Becroft D
Am J Med Genet 1997 Aug 22;71(3):341-7. doi: 10.1002/(sici)1096-8628(19970822)71:3<341::aid-ajmg16>3.0.co;2-k. PMID: 9268106

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