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Regressive spondylometaphyseal dysplasia(PHASK; SKPHA)

MedGen UID:
1648288
Concept ID:
C4747922
Disease or Syndrome
Synonym: PELGER-HUET ANOMALY WITH MILD SKELETAL ANOMALIES
SNOMED CT: Regressive spondylometaphyseal dysplasia (1237412001)
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
 
Gene (location): LBR (1q42.12)
 
Monarch Initiative: MONDO:0018663
OMIM®: 618019
Orphanet: ORPHA448267

Definition

Rhizomelic skeletal dysplasia with or without Pelger-Huet anomaly (SKPHA) is an autosomal recessive disorder characterized by rhizomelic skeletal dysplasia of variable severity with or without abnormal nuclear shape and chromatin organization in blood granulocytes (Hoffmann et al., 2002; Borovik et al., 2013; Collins et al., 2020). Initial skeletal features may improve with age (Sobreira et al., 2014). [from OMIM]

Clinical features

From HPO
Brachydactyly
MedGen UID:
67454
Concept ID:
C0221357
Congenital Abnormality
Digits that appear disproportionately short compared to the hand/foot. The word brachydactyly is used here to describe a series distinct patterns of shortened digits (brachydactyly types A-E). This is the sense used here.
Limb undergrowth
MedGen UID:
116086
Concept ID:
C0239399
Finding
Limb shortening because of underdevelopment of one or more bones of the extremities.
Knee flexion contracture
MedGen UID:
98042
Concept ID:
C0409355
Finding
A type of knee joint contracture in which the knee is in a fixed bent (flexed) configuration such that it cannot be straightened actively or passively.
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.
Short 4th metacarpal
MedGen UID:
327074
Concept ID:
C1840309
Finding
Short fourth metacarpal bone.
Radial bowing
MedGen UID:
347136
Concept ID:
C1859399
Anatomical Abnormality
A bending or abnormal curvature of the radius.
Bowed humerus
MedGen UID:
395269
Concept ID:
C1859460
Finding
A bending or abnormal curvature of the humerus.
Short 5th metacarpal
MedGen UID:
348858
Concept ID:
C1861388
Finding
Short fifth metacarpal bone.
Rhizomelia
MedGen UID:
357122
Concept ID:
C1866730
Congenital Abnormality
Disproportionate shortening of the proximal segment of limbs (i.e. the femur and humerus).
Limited elbow extension
MedGen UID:
401158
Concept ID:
C1867103
Finding
Limited ability to straighten the arm at the elbow joint.
Broad hallux
MedGen UID:
401165
Concept ID:
C1867131
Finding
Visible increase in width of the hallux without an increase in the dorso-ventral dimension.
Disproportionate short-limb short stature
MedGen UID:
342370
Concept ID:
C1849937
Finding
A type of disproportionate short stature characterized by a short limbs but an average-sized trunk.
Mild short stature
MedGen UID:
461427
Concept ID:
C3150077
Finding
A mild degree of short stature, more than -2 SD but not more than -3 SD from mean corrected for age and sex.
Protuberant abdomen
MedGen UID:
340750
Concept ID:
C1854928
Finding
A thrusting or bulging out of the abdomen.
Delayed ability to walk
MedGen UID:
66034
Concept ID:
C0241726
Finding
A failure to achieve the ability to walk at an appropriate developmental stage. Most children learn to walk in a series of stages, and learn to walk short distances independently between 12 and 15 months.
Joint dislocation
MedGen UID:
41614
Concept ID:
C0012691
Injury or Poisoning
Displacement or malalignment of joints.
Kyphosis
MedGen UID:
44042
Concept ID:
C0022821
Anatomical Abnormality
Exaggerated anterior convexity of the thoracic vertebral column.
Hyperlordosis
MedGen UID:
9805
Concept ID:
C0024003
Finding
Abnormally increased curvature (anterior concavity) of the lumbar or cervical spine.
Hypotonia
MedGen UID:
10133
Concept ID:
C0026827
Finding
Hypotonia is an abnormally low muscle tone (the amount of tension or resistance to movement in a muscle). Even when relaxed, muscles have a continuous and passive partial contraction which provides some resistance to passive stretching. Hypotonia thus manifests as diminished resistance to passive stretching. Hypotonia is not the same as muscle weakness, although the two conditions can co-exist.
Platybasia
MedGen UID:
45959
Concept ID:
C0032209
Congenital Abnormality
A developmental malformation of the occipital bone and upper end of the cervical spine, in which the latter appears to have pushed the floor of the occipital bone upward such that there is an abnormal flattening of the skull base.
Frontal bossing
MedGen UID:
67453
Concept ID:
C0221354
Congenital Abnormality
Bilateral bulging of the lateral frontal bone prominences with relative sparing of the midline.
Camptodactyly
MedGen UID:
195780
Concept ID:
C0685409
Congenital Abnormality
The distal interphalangeal joint and/or the proximal interphalangeal joint of the fingers or toes cannot be extended to 180 degrees by either active or passive extension.
Thoracolumbar scoliosis
MedGen UID:
196671
Concept ID:
C0749379
Anatomical Abnormality
Short femoral neck
MedGen UID:
373033
Concept ID:
C1836184
Finding
An abnormally short femoral neck (which is the process of bone, connecting the femoral head with the femoral shaft).
Metaphyseal cupping
MedGen UID:
323062
Concept ID:
C1837082
Finding
Metaphyseal cupping refers to an inward bulging of the metaphyseal profile giving the metaphysis a cup-like appearance.
Thoracic hypoplasia
MedGen UID:
373339
Concept ID:
C1837482
Congenital Abnormality
Metaphyseal irregularity
MedGen UID:
325478
Concept ID:
C1838662
Finding
Irregularity of the normally smooth surface of the metaphyses.
Platyspondyly
MedGen UID:
335010
Concept ID:
C1844704
Finding
A flattened vertebral body shape with reduced distance between the vertebral endplates.
Joint hypermobility
MedGen UID:
336793
Concept ID:
C1844820
Finding
The capability that a joint (or a group of joints) has to move, passively and/or actively, beyond normal limits along physiological axes.
Relative macrocephaly
MedGen UID:
338607
Concept ID:
C1849075
Congenital Abnormality
A relatively mild degree of macrocephaly in which the head circumference is not above two standard deviations from the mean, but appears dysproportionately large when other factors such as body stature are taken into account.
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.
Short long bone
MedGen UID:
344385
Concept ID:
C1854912
Finding
One or more abnormally short long bone.
Thoracolumbar kyphosis
MedGen UID:
383679
Concept ID:
C1855418
Anatomical Abnormality
Hyperconvexity of the thoracolumbar spine producing a rounded or humped appearance.
Ovoid vertebral bodies
MedGen UID:
344549
Concept ID:
C1855665
Finding
When viewed in lateral radiographs, vertebral bodies have a roughly rectangular configuration. This term applies if the vertebral body appears rounded or oval.
Femoral bowing
MedGen UID:
347888
Concept ID:
C1859461
Finding
Bowing (abnormal curvature) of the femur.
Small foramen magnum
MedGen UID:
348813
Concept ID:
C1861217
Finding
An abnormal narrowing of the foramen magnum.
Thoracic platyspondyly
MedGen UID:
400049
Concept ID:
C1862428
Finding
A flattened vertebral body shape with reduced distance between the vertebral endplates affecting the thoracic spine.
Horizontal ribs
MedGen UID:
812840
Concept ID:
C3806510
Finding
A horizontal (flat) conformation of the ribs, the long curved bones that form the rib cage and normally progressively oblique (slanted) from ribs 1 through 9, then less slanted through rib 12.
Metaphyseal dysplasia
MedGen UID:
1677924
Concept ID:
C5194606
Disease or Syndrome
The presence of dysplastic regions in metaphyseal regions.
Hyposegmentation of neutrophil nuclei
MedGen UID:
892291
Concept ID:
C4023351
Cell or Molecular Dysfunction
Hyposegmented (hypolobulated) or bilobed neutrophil nuclei.
Depressed nasal bridge
MedGen UID:
373112
Concept ID:
C1836542
Finding
Posterior positioning of the nasal root in relation to the overall facial profile for age.
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.
Nevus flammeus of the forehead
MedGen UID:
376454
Concept ID:
C1848850
Finding
Naevus flammeus localized in the skin of the forehead.
Inversion of nipple
MedGen UID:
82844
Concept ID:
C0269269
Anatomical Abnormality
The presence of nipples that instead of pointing outward are retracted inwards.
Wide intermamillary distance
MedGen UID:
473489
Concept ID:
C1827524
Finding
A larger than usual distance between the left and right nipple.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVRegressive spondylometaphyseal dysplasia

Recent clinical studies

Diagnosis

Turgut GT, Güleç Ç, Sarac Sivrikoz T, Kale H, Karaman B, Nishimura G, Altunoglu U
Am J Med Genet A 2022 Jan;188(1):253-258. Epub 2021 Aug 31 doi: 10.1002/ajmg.a.62479. PMID: 34467646

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