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Acrofacial dysostosis Rodriguez type

MedGen UID:
349730
Concept ID:
C1860119
Disease or Syndrome
Synonyms: ACROFACIAL DYSOSTOSIS SYNDROME OF RODRIGUEZ; Rodriguez lethal acrofacial dysostosis syndrome
SNOMED CT: Acrofacial dysostosis Rodriguez type (720430002)
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).
Autosomal dominant inheritance
MedGen UID:
141047
Concept ID:
C0443147
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 heterozygotes. In the context of medical genetics, an autosomal dominant disorder is caused when a single copy of the mutant allele is present. Males and females are affected equally, and can both transmit the disorder with a risk of 50% for each child of inheriting the mutant allele.
 
Monarch Initiative: MONDO:0008714
OMIM®: 201170
Orphanet: ORPHA1788

Definition

A multiple malformation syndrome in which mandibulofacial dysostosis and severe limb reduction defects are associated with complex malformations of different organs and systems especially the central nervous system, urogenital tract, heart, and lungs. The mandibulofacial defect causes death by respiratory distress. Limb reduction is severe and includes shoulder and pelvis hypoplasia, phocomelia with humerus hypoplasia, absent radius and ulna, complete absence of long bones of the legs, and various hand anomalies, predominantly preaxial reduction. These infants also show facial dysmorphism and ear anomalies. The condition is a rare with an autosomal recessive mode of inheritance. The prognosis is poor and this condition leads to death in utero or shortly after birth. [from SNOMEDCT_US]

Clinical features

From HPO
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).
Triphalangeal thumb
MedGen UID:
66029
Concept ID:
C0241397
Congenital Abnormality
A thumb with three phalanges in a single, proximo-distal axis. Thus, this term applies if the thumb has an accessory phalanx, leading to a digit like appearance of the thumb.
Single transverse palmar crease
MedGen UID:
96108
Concept ID:
C0424731
Finding
The distal and proximal transverse palmar creases are merged into a single transverse palmar crease.
Overlapping toe
MedGen UID:
182531
Concept ID:
C0920299
Anatomical Abnormality
Describes a foot digit resting on the dorsal surface of an adjacent digit when the foot is at rest. Initially clawing may be dynamic and only noticeable on walking. Over time the plantar plate tears, subluxation occurs at the metatarsophalangeal joint (MTPJ), and the deformity becomes permanent.
Absent forearm
MedGen UID:
278055
Concept ID:
C1408532
Finding
Fibular hypoplasia
MedGen UID:
316909
Concept ID:
C1832119
Finding
Underdevelopment of the fibula.
Short tibia
MedGen UID:
338005
Concept ID:
C1850259
Finding
Underdevelopment (reduced size) of the tibia.
Oligodactyly
MedGen UID:
854358
Concept ID:
C3887496
Congenital Abnormality
A developmental defect resulting in the presence of fewer than the normal number of digits.
Clinodactyly
MedGen UID:
1644094
Concept ID:
C4551485
Congenital Abnormality
An angulation of a digit at an interphalangeal joint in the plane of the palm (finger) or sole (toe).
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).
Low-set ears
MedGen UID:
65980
Concept ID:
C0239234
Congenital Abnormality
Upper insertion of the ear to the scalp below an imaginary horizontal line drawn between the inner canthi of the eye and extending posteriorly to the ear.
Posteriorly rotated ears
MedGen UID:
96566
Concept ID:
C0431478
Congenital Abnormality
A type of abnormal location of the ears in which the position of the ears is characterized by posterior rotation (the superior part of the ears is rotated towards the back of the head, and the inferior part of the ears towards the front).
Micrognathia
MedGen UID:
44428
Concept ID:
C0025990
Congenital Abnormality
Developmental hypoplasia of the mandible.
11 pairs of ribs
MedGen UID:
326950
Concept ID:
C1839731
Finding
Presence of only 11 pairs of ribs.
Wide anterior fontanel
MedGen UID:
400926
Concept ID:
C1866134
Finding
Enlargement of the anterior fontanelle with respect to age-dependent norms.
Narrow mouth
MedGen UID:
44435
Concept ID:
C0026034
Congenital Abnormality
Distance between the commissures of the mouth more than 2 SD below the mean. Alternatively, an apparently decreased width of the oral aperture (subjective).
High palate
MedGen UID:
66814
Concept ID:
C0240635
Congenital Abnormality
Height of the palate more than 2 SD above the mean (objective) or palatal height at the level of the first permanent molar more than twice the height of the teeth (subjective).
Prominent nose
MedGen UID:
98423
Concept ID:
C0426415
Finding
Distance between subnasale and pronasale more than two standard deviations above the mean, or alternatively, an apparently increased anterior protrusion of the nasal tip.
Wide nasal bridge
MedGen UID:
341441
Concept ID:
C1849367
Finding
Increased breadth of the nasal bridge (and with it, the nasal root).
Short philtrum
MedGen UID:
350006
Concept ID:
C1861324
Finding
Distance between nasal base and midline upper lip vermilion border more than 2 SD below the mean. Alternatively, an apparently decreased distance between nasal base and midline upper lip vermilion border.
Thin skin
MedGen UID:
140848
Concept ID:
C0423757
Finding
Reduction in thickness of the skin, generally associated with a loss of suppleness and elasticity of the skin.
Deep-set nails
MedGen UID:
479383
Concept ID:
C3277753
Finding
Deeply placed nails.
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).
Deeply set eye
MedGen UID:
473112
Concept ID:
C0423224
Finding
An eye that is more deeply recessed into the plane of the face than is typical.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVAcrofacial dysostosis Rodriguez type
Follow this link to review classifications for Acrofacial dysostosis Rodriguez type in Orphanet.

Recent clinical studies

Etiology

Marques F, Tenney J, Duran I, Martin J, Nevarez L, Pogue R, Krakow D, Cohn DH, Li B
PLoS Genet 2016 Sep;12(9):e1006307. Epub 2016 Sep 13 doi: 10.1371/journal.pgen.1006307. PMID: 27622494Free PMC Article

Diagnosis

Drivas TG, Taylor JA, Zackai EH
Am J Med Genet A 2019 Jun;179(6):1063-1068. Epub 2019 Mar 28 doi: 10.1002/ajmg.a.61121. PMID: 30924273
McPherson E, Zaleski C, Ye Z, Lin S
Am J Med Genet A 2014 Jul;164A(7):1841-5. Epub 2014 Apr 8 doi: 10.1002/ajmg.a.36555. PMID: 24715698
Gana S, Gentilin B, Bianchi V, Gorla S, Ceriani F, Melloni G, Lalatta F
Clin Dysmorphol 2013 Oct;22(4):135-139. doi: 10.1097/MCD.0b013e32836351c8. PMID: 23811969

Clinical prediction guides

Irving MD, Dimitrov BI, Wessels M, Holder-Espinasse M, Chitayat D, Simpson MA
Am J Med Genet A 2016 Dec;170(12):3133-3137. Epub 2016 Sep 19 doi: 10.1002/ajmg.a.37946. PMID: 27642715
Marques F, Tenney J, Duran I, Martin J, Nevarez L, Pogue R, Krakow D, Cohn DH, Li B
PLoS Genet 2016 Sep;12(9):e1006307. Epub 2016 Sep 13 doi: 10.1371/journal.pgen.1006307. PMID: 27622494Free PMC Article

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