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Asphyxiating thoracic dystrophy 3(ATD3; SRPS1; SRPS2B; SRTD3)

MedGen UID:
19860
Concept ID:
C0036069
Disease or Syndrome
Synonyms: Polydactyly with neonatal chondrodystrophy type 1; Polydactyly with neonatal chondrodystrophy type III; POLYDACTYLY WITH NEONATAL CHONDRODYSTROPHY, TYPE I; Saldino-Noonan Syndrome; Short rib polydactyly syndrome 2B; Short Rib Polydactyly Syndrome, Verma-Naumoff Type; Short rib-polydactyly syndrome type 3; Short rib-polydactyly syndrome Saldino-Noonan type; Short rib-polydactyly syndrome type 1; Short-rib polydactyly syndrome type I; Short-rib polydactyly syndrome type III; Short-rib thoracic dysplasia 3 with or without polydactyly; SHORT-RIB THORACIC DYSPLASIA 3/6 WITH POLYDACTYLY, DIGENIC; SRPS type 1; SRPS type 3; Verma Naumoff syndrome
SNOMED CT: Short rib polydactyly syndrome Saldino Noonan type (726032008); Saldino Noonan syndrome (726032008); Short rib polydactyly syndrome type 1 (726032008); Short rib polydactyly syndrome type I (726032008)
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): DYNC2H1 (11q22.3)
 
Monarch Initiative: MONDO:0013127
OMIM®: 613091
Orphanet: ORPHA93271

Definition

Short-rib thoracic dysplasia (SRTD) with or without polydactyly refers to a group of autosomal recessive skeletal ciliopathies that are characterized by a constricted thoracic cage, short ribs, shortened tubular bones, and a 'trident' appearance of the acetabular roof. SRTD encompasses Ellis-van Creveld syndrome (EVC) and the disorders previously designated as Jeune syndrome or asphyxiating thoracic dystrophy (ATD), short rib-polydactyly syndrome (SRPS), and Mainzer-Saldino syndrome (MZSDS). Polydactyly is variably present, and there is phenotypic overlap in the various forms of SRTDs, which differ by visceral malformation and metaphyseal appearance. Nonskeletal involvement can include cleft lip/palate as well as anomalies of major organs such as the brain, eye, heart, kidneys, liver, pancreas, intestines, and genitalia. Some forms of SRTD are lethal in the neonatal period due to respiratory insufficiency secondary to a severely restricted thoracic cage, whereas others are compatible with life (summary by Huber and Cormier-Daire, 2012 and Schmidts et al., 2013). There is phenotypic overlap with the cranioectodermal dysplasias (Sensenbrenner syndrome; see CED1, 218330). For a discussion of genetic heterogeneity of short-rib thoracic dysplasia, see SRTD1 (208500). [from OMIM]

Clinical features

From HPO
Polycystic kidney disease
MedGen UID:
9639
Concept ID:
C0022680
Disease or Syndrome
The presence of multiple cysts in both kidneys.
Ambiguous genitalia
MedGen UID:
78596
Concept ID:
C0266362
Congenital Abnormality
A genital phenotype that is not clearly assignable to a single gender. Ambiguous genitalia can be evaluated using the Prader scale
Enlarged kidney
MedGen UID:
108156
Concept ID:
C0542518
Finding
An abnormal increase in the size of the kidney.
Renal dysplasia
MedGen UID:
760690
Concept ID:
C3536714
Congenital Abnormality
The presence of developmental dysplasia of the kidney.
Micropenis
MedGen UID:
1633603
Concept ID:
C4551492
Congenital Abnormality
Abnormally small penis. At birth, the normal penis is about 3 cm (stretched length from pubic tubercle to tip of penis) with micropenis less than 2.0-2.5 cm.
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).
Postaxial polydactyly
MedGen UID:
67394
Concept ID:
C0220697
Congenital Abnormality
Polydactyly refers to the occurrence of supernumerary digits and is the most frequent of congenital hand and foot deformities. Based on the location of the extra digits, polydactyly can be classified into preaxial, involving the thumb or great toe; postaxial, affecting the fifth digit; and central, involving the 3 central digits. Postaxial polydactyly (PAP) is further subclassified into 2 types: in type A, a well-formed extra digit articulates with the fifth or a sixth metacarpal, whereas in type B, a rudimentary, poorly developed extra digit is present (summary by Umm-e-Kalsoom et al., 2012). Genetic Heterogeneity of Postaxial Polydactyly Other forms of postaxial polydactyly type A include PAPA2 (602085) on chromosome 13q21; PAPA3 (607324) on chromosome 19p13; PAPA4 (608562) on chromosome 7q22; PAPA5 (263450) on chromosome 13q13; PAPA6 (615226), caused by mutation in the ZNF141 gene (194648) on chromosome 4p16; PAPA7 (617642), caused by mutation in the IQCE gene (617631) on chromosome 7p22; PAPA8 (618123), caused by mutation in the GLI1 gene (165220) on chromosome 12q13; PAPA9 (618219), caused by mutation in the CIBAR1 gene (617273) on chromosome 8q22; and PAPA10 (618498), caused by mutation in the KIAA0825 gene (617266) on chromosome 5q15.
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.
Preaxial polydactyly
MedGen UID:
87498
Concept ID:
C0345354
Congenital Abnormality
A form of polydactyly in which the extra digit or digits are localized on the side of the thumb or great toe.
Fibular hypoplasia
MedGen UID:
316909
Concept ID:
C1832119
Finding
Underdevelopment of the fibula.
Hypoplasia of the ulna
MedGen UID:
395934
Concept ID:
C1860614
Congenital Abnormality
Underdevelopment of the ulna.
Absent tibia
MedGen UID:
478374
Concept ID:
C3276744
Finding
Absence of the tibia.
Acetabular spurs
MedGen UID:
814600
Concept ID:
C3808270
Finding
The presence of osteophytes (bone spurs), i.e., of bony projections originating from the acetabulum.
Short digit
MedGen UID:
893063
Concept ID:
C4023124
Finding
One or more digit that appears disproportionately short compared to the hand/foot, whereby either the entire digit or a specific phalanx is shortened.
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).
Imperforate anus
MedGen UID:
1997
Concept ID:
C0003466
Congenital Abnormality
Congenital absence of the anus, i.e., the opening at the bottom end of the intestinal tract.
Intestinal malrotation
MedGen UID:
113153
Concept ID:
C0221210
Congenital Abnormality
An abnormality of the intestinal rotation and fixation that normally occurs during the development of the gut. This can lead to volvulus, or twisting of the intestine that causes obstruction and necrosis.
Hamartoma of tongue
MedGen UID:
98465
Concept ID:
C0431565
Finding
A benign (noncancerous) tumorlike malformation made up of an abnormal mixture of cells and tissues that originates in the tongue.
Corpus callosum, agenesis of
MedGen UID:
104498
Concept ID:
C0175754
Congenital Abnormality
The corpus callosum is the largest fiber tract in the central nervous system and the major interhemispheric fiber bundle in the brain. Formation of the corpus callosum begins as early as 6 weeks' gestation, with the first fibers crossing the midline at 11 to 12 weeks' gestation, and completion of the basic shape by age 18 to 20 weeks (Schell-Apacik et al., 2008). Agenesis of the corpus callosum (ACC) is one of the most frequent malformations in brain with a reported incidence ranging between 0.5 and 70 in 10,000 births. ACC is a clinically and genetically heterogeneous condition, which can be observed either as an isolated condition or as a manifestation in the context of a congenital syndrome (see MOLECULAR GENETICS and Dobyns, 1996). Also see mirror movements-1 and/or agenesis of the corpus callosum (MRMV1; 157600). Schell-Apacik et al. (2008) noted that there is confusion in the literature regarding radiologic terminology concerning partial absence of the corpus callosum, where various designations have been used, including hypogenesis, hypoplasia, partial agenesis, or dysgenesis.
Cerebellar cyst
MedGen UID:
339835
Concept ID:
C1847762
Finding
Scoliosis
MedGen UID:
11348
Concept ID:
C0036439
Disease or Syndrome
The presence of an abnormal lateral curvature of the spine.
Lateral clavicle hook
MedGen UID:
98426
Concept ID:
C0426805
Finding
An excessive upward convexity of the lateral clavicle.
Short ribs
MedGen UID:
98094
Concept ID:
C0426817
Finding
Reduced rib length.
Metaphyseal spurs
MedGen UID:
318762
Concept ID:
C1832988
Finding
Bony outgrowths that extend laterally from the margin of the metaphysis.
Thoracic hypoplasia
MedGen UID:
373339
Concept ID:
C1837482
Congenital Abnormality
Metaphyseal widening
MedGen UID:
341364
Concept ID:
C1849039
Finding
Abnormal widening of the metaphyseal regions of long bones.
Short long bone
MedGen UID:
344385
Concept ID:
C1854912
Finding
One or more abnormally short long bone.
Femoral bowing
MedGen UID:
347888
Concept ID:
C1859461
Finding
Bowing (abnormal curvature) of the femur.
Cone-shaped epiphysis
MedGen UID:
351282
Concept ID:
C1865037
Finding
Cone-shaped epiphyses (also known as coned epiphyses) are epiphyses that invaginate into cupped metaphyses. That is, the epiphysis has a cone-shaped distal extension resulting from increased growth of the central portion of the epiphysis relative to its periphery.
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.
Cleft upper lip
MedGen UID:
40327
Concept ID:
C0008924
Congenital Abnormality
A gap or groove in the upper lip. This is a congenital defect resulting from nonfusion of tissues of the lip during embryonal development.
Bifid tongue
MedGen UID:
82731
Concept ID:
C0266111
Congenital Abnormality
Tongue with a median apical indentation or fork.
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).

Term Hierarchy

Professional guidelines

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Recent clinical studies

Etiology

Peng Y, Zhou L, Chen J, Huang X, Pang J, Liu J, Tang W, Yang S, Liang C, Xie W
BMC Med Genomics 2023 Dec 7;16(1):318. doi: 10.1186/s12920-023-01753-y. PMID: 38062428Free PMC Article
Antony D, Brunner HG, Schmidts M
Cells 2021 Jul 25;10(8) doi: 10.3390/cells10081885. PMID: 34440654Free PMC Article
Handa A, Voss U, Hammarsjö A, Grigelioniene G, Nishimura G
Jpn J Radiol 2020 Mar;38(3):193-206. Epub 2020 Jan 21 doi: 10.1007/s11604-020-00920-w. PMID: 31965514
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Diagnosis

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BMC Med Genomics 2023 Dec 7;16(1):318. doi: 10.1186/s12920-023-01753-y. PMID: 38062428Free PMC Article
Piceci-Sparascio F, Micale L, Torres B, Guida V, Consoli F, Torrente I, Onori A, Frustaci E, D'Asdia MC, Petrizzelli F, Bernardini L, Mancini C, Soli F, Cocciadiferro D, Guadagnolo D, Mastromoro G, Putotto C, Fontana F, Brunetti-Pierri N, Novelli A, Pizzuti A, Marino B, Digilio MC, Mazza T, Dallapiccola B, Ruiz-Perez VL, Tartaglia M, Castori M, De Luca A
Eur J Hum Genet 2023 Apr;31(4):479-484. Epub 2023 Jan 4 doi: 10.1038/s41431-022-01276-7. PMID: 36599940Free PMC Article
Zhang W, Taylor SP, Ennis HA, Forlenza KN, Duran I, Li B, Sanchez JAO, Nevarez L, Nickerson DA, Bamshad M; University of Washington Center for Mendelian Genomics, Lachman RS, Krakow D, Cohn DH
Hum Mutat 2018 Jan;39(1):152-166. Epub 2017 Nov 6 doi: 10.1002/humu.23362. PMID: 29068549Free PMC Article
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Prognosis

Okiro P, Wainwright H, Spranger J, Beighton P
Pediatr Dev Pathol 2015 Jan-Feb;18(1):40-8. Epub 2014 Dec 1 doi: 10.2350/14-05-1496-OA.1. PMID: 25437139
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Clinical prediction guides

Xia CL, Xiao SQ, Yang X, Liu CX, Qiu H, Jiang HK, Li-Ling J, Lyu Y
Mol Med Rep 2021 Jun;23(6) Epub 2021 Apr 13 doi: 10.3892/mmr.2021.12065. PMID: 33846808
Okiro P, Wainwright H, Spranger J, Beighton P
Pediatr Dev Pathol 2015 Jan-Feb;18(1):40-8. Epub 2014 Dec 1 doi: 10.2350/14-05-1496-OA.1. PMID: 25437139
Huber C, Cormier-Daire V
Am J Med Genet C Semin Med Genet 2012 Aug 15;160C(3):165-74. Epub 2012 Jul 12 doi: 10.1002/ajmg.c.31336. PMID: 22791528
Baujat G, Le Merrer M
Orphanet J Rare Dis 2007 Jun 4;2:27. doi: 10.1186/1750-1172-2-27. PMID: 17547743Free PMC Article
Sillence DO
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