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Armfield syndrome(MRXSA)

MedGen UID:
375800
Concept ID:
C1846057
Disease or Syndrome
Synonym: MRXSA
Modes of inheritance:
X-linked recessive inheritance
MedGen UID:
375779
Concept ID:
C1845977
Finding
Source: Orphanet
A mode of inheritance that is observed for recessive traits related to a gene encoded on the X chromosome. In the context of medical genetics, X-linked recessive disorders manifest in males (who have one copy of the X chromosome and are thus hemizygotes), but generally not in female heterozygotes who have one mutant and one normal allele.
 
Gene (location): FAM50A (Xq28)
 
Monarch Initiative: MONDO:0010284
OMIM®: 300261
Orphanet: ORPHA85276

Definition

MRXSA is an X-linked recessive neurodevelopmental disorder characterized by global developmental delay with impaired intellectual development, usually accompanied by walking difficulties and poor or absent speech. Affected individuals have dysmorphic features, including large head circumference, downslanting palpebral fissures, bulbous nose, high-arched palate, short stature, and small hands and feet. Ocular anomalies, including strabismus, exotropia, myopia, and keratoconus, are common. Some patients may develop seizures. Additional variable features, such as mild congenital heart defects, joint stiffness, renal anomalies, and hemangiomas, may also be present (summary by Lee et al., 2020). [from OMIM]

Clinical features

From HPO
Small hand
MedGen UID:
108279
Concept ID:
C0575802
Finding
Disproportionately small hand.
Short foot
MedGen UID:
376415
Concept ID:
C1848673
Finding
A measured foot length that is more than 2 SD below the mean for a newborn of 27 - 41 weeks gestation, or foot that is less than the 3rd centile for individuals from birth to 16 years of age (objective). Alternatively, a foot that appears disproportionately short (subjective).
Abnormal hand morphology
MedGen UID:
870655
Concept ID:
C4025109
Anatomical Abnormality
Any structural anomaly of the hand.
Short stature
MedGen UID:
87607
Concept ID:
C0349588
Finding
A height below that which is expected according to age and gender norms. Although there is no universally accepted definition of short stature, many refer to "short stature" as height more than 2 standard deviations below the mean for age and gender (or below the 3rd percentile for age and gender dependent norms).
Seizure
MedGen UID:
20693
Concept ID:
C0036572
Sign or Symptom
A seizure is an intermittent abnormality of nervous system physiology characterized by a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain.
Intellectual disability
MedGen UID:
811461
Concept ID:
C3714756
Mental or Behavioral Dysfunction
Intellectual disability, previously referred to as mental retardation, is characterized by subnormal intellectual functioning that occurs during the developmental period. It is defined by an IQ score below 70.
Malar flattening
MedGen UID:
347616
Concept ID:
C1858085
Finding
Underdevelopment of the malar prominence of the jugal bone (zygomatic bone in mammals), appreciated in profile, frontal view, and/or by palpation.
Prominent forehead
MedGen UID:
373291
Concept ID:
C1837260
Finding
Forward prominence of the entire forehead, due to protrusion of the frontal bone.
Midface retrusion
MedGen UID:
339938
Concept ID:
C1853242
Anatomical Abnormality
Posterior positions and/or vertical shortening of the infraorbital and perialar regions, or increased concavity of the face and/or reduced nasolabial angle.
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).
Glaucoma
MedGen UID:
42224
Concept ID:
C0017601
Disease or Syndrome
Glaucoma refers loss of retinal ganglion cells in a characteristic pattern of optic neuropathy usually associated with increased intraocular pressure.
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.
Cataract
MedGen UID:
39462
Concept ID:
C0086543
Disease or Syndrome
A cataract is an opacity or clouding that develops in the crystalline lens of the eye or in its capsule.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVArmfield syndrome
Follow this link to review classifications for Armfield syndrome in Orphanet.

Recent clinical studies

Etiology

Goldstein NA, Armfield DR, Kingsley LA, Borland LM, Allen GC, Post JC
Arch Otolaryngol Head Neck Surg 1998 Feb;124(2):171-6. doi: 10.1001/archotol.124.2.171. PMID: 9485108

Diagnosis

Haghshenas S, Levy MA, Kerkhof J, Aref-Eshghi E, McConkey H, Balci T, Siu VM, Skinner CD, Stevenson RE, Sadikovic B, Schwartz C
Int J Mol Sci 2021 Jan 23;22(3) doi: 10.3390/ijms22031111. PMID: 33498634Free PMC Article
Armfield DR, Kim DH, Towers JD, Bradley JP, Robertson DD
Clin Sports Med 2006 Oct;25(4):803-42. doi: 10.1016/j.csm.2006.06.011. PMID: 16962427

Prognosis

Armfield K, Nelson R, Lubs HA, Häne B, Schroer RJ, Arena F, Schwartz CE, Stevenson RE
Am J Med Genet 1999 Jul 30;85(3):236-42. doi: 10.1002/(sici)1096-8628(19990730)85:3<236::aid-ajmg10>3.0.co;2-9. PMID: 10398235
Goldstein NA, Armfield DR, Kingsley LA, Borland LM, Allen GC, Post JC
Arch Otolaryngol Head Neck Surg 1998 Feb;124(2):171-6. doi: 10.1001/archotol.124.2.171. PMID: 9485108

Clinical prediction guides

Armfield K, Nelson R, Lubs HA, Häne B, Schroer RJ, Arena F, Schwartz CE, Stevenson RE
Am J Med Genet 1999 Jul 30;85(3):236-42. doi: 10.1002/(sici)1096-8628(19990730)85:3<236::aid-ajmg10>3.0.co;2-9. PMID: 10398235
Goldstein NA, Armfield DR, Kingsley LA, Borland LM, Allen GC, Post JC
Arch Otolaryngol Head Neck Surg 1998 Feb;124(2):171-6. doi: 10.1001/archotol.124.2.171. PMID: 9485108

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