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Rhizomelic limb shortening with dysmorphic features(RLSDF)

MedGen UID:
1720321
Concept ID:
C5394173
Disease or Syndrome
Synonyms: RHIZOMELIC LIMB SHORTENING WITH DYSMORPHIC FEATURES; RLSDF
 
Gene (location): PKDCC (2p21)
 
Monarch Initiative: MONDO:0032935
OMIM®: 618821

Definition

Rhizomelic limb shortening with dysmorphic features (RLSDF) is characterized by rhizomelic shortening of the extremities, predominantly of the upper limbs, and variable dysmorphic features, including macrocephaly, prominent forehead, hypertelorism, depressed or broad nasal bridge, and micrognathia. Hearing loss has also been observed (Sajan et al., 2019; Pagnamenta et al., 2023). [from OMIM]

Clinical features

From HPO
Arthralgia
MedGen UID:
13917
Concept ID:
C0003862
Sign or Symptom
Joint pain.
Stage 1 chronic kidney disease
MedGen UID:
378390
Concept ID:
C2316401
Disease or Syndrome
A type of chronic kidney disease with normal or increased glomerular filtration rate (GFR at least 90 mL/min/1.73 m2).
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.
Short thumb
MedGen UID:
98469
Concept ID:
C0431890
Congenital Abnormality
Hypoplasia (congenital reduction in size) of the thumb.
Short 5th finger
MedGen UID:
334269
Concept ID:
C1842878
Congenital Abnormality
Hypoplasia (congenital reduction in size) of the fifth finger, also known as the little finger.
Rhizomelia
MedGen UID:
357122
Concept ID:
C1866730
Congenital Abnormality
Disproportionate shortening of the proximal segment of limbs (i.e. the femur and humerus).
Clinodactyly of the 3rd finger
MedGen UID:
868094
Concept ID:
C4022485
Congenital Abnormality
Patent foramen ovale
MedGen UID:
8891
Concept ID:
C0016522
Congenital Abnormality
Failure of the foramen ovale to seal postnatally, leaving a potential conduit between the left and right cardiac atria.
Obesity
MedGen UID:
18127
Concept ID:
C0028754
Disease or Syndrome
Accumulation of substantial excess body fat.
Brisk reflexes
MedGen UID:
382164
Concept ID:
C2673700
Finding
Tendon reflexes that are noticeably more active than usual (conventionally denoted 3+ on clinical examination). Brisk reflexes may or may not indicate a neurological lesion. They are distinguished from hyperreflexia by the fact that hyerreflexia is characterized by hyperactive repeating (clonic) reflexes, which are considered to be always abnormal.
Delayed CNS myelination
MedGen UID:
867393
Concept ID:
C4021758
Anatomical Abnormality
Delayed myelination in the central nervous system.
Micrognathia
MedGen UID:
44428
Concept ID:
C0025990
Congenital Abnormality
Developmental hypoplasia of the mandible.
Plagiocephaly
MedGen UID:
78562
Concept ID:
C0265529
Congenital Abnormality
Asymmetric head shape, which is usually a combination of unilateral occipital flattening with ipsilateral frontal prominence, leading to rhomboid cranial shape.
Patellar dislocation
MedGen UID:
253896
Concept ID:
C1135812
Injury or Poisoning
The kneecap normally is located within the groove termed trochlea on the distal femur and can slide up and down in it. Patellar dislocation occurs if the patella fully dislocates out of the groove.
Hyperextensibility of the finger joints
MedGen UID:
334982
Concept ID:
C1844577
Finding
The ability of the finger joints to move beyond their normal range of motion.
Limited shoulder movement
MedGen UID:
341979
Concept ID:
C1851313
Finding
A limitation of the range of movement of the shoulder joint.
Macrocephaly
MedGen UID:
745757
Concept ID:
C2243051
Finding
Occipitofrontal (head) circumference greater than 97th centile compared to appropriate, age matched, sex-matched normal standards. Alternatively, a apparently increased size of the cranium.
Congenital laryngomalacia
MedGen UID:
120500
Concept ID:
C0264303
Anatomical Abnormality
Laryngomalacia is a congenital abnormality of the laryngeal cartilage in which the cartilage is floppy and prolapses over the larynx during inspiration.
Downslanted palpebral fissures
MedGen UID:
98391
Concept ID:
C0423110
Finding
The palpebral fissure inclination is more than two standard deviations below the mean.
Short neck
MedGen UID:
99267
Concept ID:
C0521525
Finding
Diminished length of the neck.
Smooth philtrum
MedGen UID:
222980
Concept ID:
C1142533
Finding
Flat skin surface, with no ridge formation in the central region of the upper lip between the nasal base and upper vermilion border.
Prominent forehead
MedGen UID:
373291
Concept ID:
C1837260
Finding
Forward prominence of the entire forehead, due to protrusion of the frontal bone.
Wide nasal bridge
MedGen UID:
341441
Concept ID:
C1849367
Finding
Increased breadth of the nasal bridge (and with it, the nasal root).
Long philtrum
MedGen UID:
351278
Concept ID:
C1865014
Finding
Distance between nasal base and midline upper lip vermilion border more than 2 SD above the mean. Alternatively, an apparently increased distance between nasal base and midline upper lip vermilion border.
Acanthosis nigricans
MedGen UID:
54
Concept ID:
C0000889
Disease or Syndrome
A dermatosis characterized by thickened, hyperpigmented plaques, typically on the intertriginous surfaces and neck.
Prominent fingertip pads
MedGen UID:
322758
Concept ID:
C1835807
Finding
A soft tissue prominence of the ventral aspects of the fingertips. The term "persistent fetal fingertip pads" is often used as a synonym, but should better not be used because it implies knowledge of history of the patient which often does not exist.
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.

Professional guidelines

PubMed

Yan L, Cao J, Zhang Y, Liu Y, Zou J, Lou B, Zhuang D, Li H
BMC Med Genomics 2023 Aug 17;16(1):190. doi: 10.1186/s12920-023-01631-7. PMID: 37592254Free PMC Article

Recent clinical studies

Etiology

Mollaoğlu E, Uludağ Alkaya D, Yıldız CA, Kasap B, Tüysüz B
Clin Genet 2023 May;103(5):574-579. Epub 2022 Dec 20 doi: 10.1111/cge.14277. PMID: 36504352
Kucińska-Chahwan A, Bijok J, Dąbkowska S, Jóźwiak A, Ilnicka A, Nowakowska B, Jakiel G, Roszkowski T
Prenat Diagn 2017 May;37(5):446-452. Epub 2017 Mar 27 doi: 10.1002/pd.5030. PMID: 28233318
Nimmo G, Monsonego S, Descartes M, Franklin J, Steinberg S, Braverman N
Am J Med Genet A 2010 Jul;152A(7):1812-7. doi: 10.1002/ajmg.a.33489. PMID: 20583171
Zannolli R, Mostardini R, Carpentieri ML, Gatti MG, Galluzzi P, Terrosi Vagnoli P, Giorgetti R, Calvieri S, Morgese G
Pediatr Dermatol 2001 Jul-Aug;18(4):332-5. doi: 10.1046/j.1525-1470.2001.01955.x. PMID: 11576410

Diagnosis

Wang J, Yu H, Zhang X, Zhou X, Tan Y, Li Z, Gu Y, Lin L
Mol Genet Genomic Med 2024 Jun;12(6):e2477. doi: 10.1002/mgg3.2477. PMID: 38860479Free PMC Article
Yan L, Cao J, Zhang Y, Liu Y, Zou J, Lou B, Zhuang D, Li H
BMC Med Genomics 2023 Aug 17;16(1):190. doi: 10.1186/s12920-023-01631-7. PMID: 37592254Free PMC Article
Mollaoğlu E, Uludağ Alkaya D, Yıldız CA, Kasap B, Tüysüz B
Clin Genet 2023 May;103(5):574-579. Epub 2022 Dec 20 doi: 10.1111/cge.14277. PMID: 36504352
Sajan SA, Ganesh J, Shinde DN, Powis Z, Scarano MI, Stone J, Winter S, Tang S
J Med Genet 2019 Dec;56(12):850-854. Epub 2018 Nov 26 doi: 10.1136/jmedgenet-2018-105639. PMID: 30478137
Kucińska-Chahwan A, Bijok J, Dąbkowska S, Jóźwiak A, Ilnicka A, Nowakowska B, Jakiel G, Roszkowski T
Prenat Diagn 2017 May;37(5):446-452. Epub 2017 Mar 27 doi: 10.1002/pd.5030. PMID: 28233318

Therapy

Bernardi P, Graziadio C, Rosa RF, Pfeil JN, Zen PR, Paskulin GA
Sao Paulo Med J 2010;128(2):99-101. doi: 10.1590/s1516-31802010000200011. PMID: 20676578Free PMC Article

Prognosis

Sajan SA, Ganesh J, Shinde DN, Powis Z, Scarano MI, Stone J, Winter S, Tang S
J Med Genet 2019 Dec;56(12):850-854. Epub 2018 Nov 26 doi: 10.1136/jmedgenet-2018-105639. PMID: 30478137
Stevens CA, Lachman RS
Am J Med Genet A 2010 Aug;152A(8):1915-8. doi: 10.1002/ajmg.a.33488. PMID: 20602491Free PMC Article
Zannolli R, Mostardini R, Carpentieri ML, Gatti MG, Galluzzi P, Terrosi Vagnoli P, Giorgetti R, Calvieri S, Morgese G
Pediatr Dermatol 2001 Jul-Aug;18(4):332-5. doi: 10.1046/j.1525-1470.2001.01955.x. PMID: 11576410

Clinical prediction guides

Pagnamenta AT, Belles RS, Salbert BA, Wentzensen IM, Guillen Sacoto MJ, Santos FJR, Caffo A, Ferla M, Banos-Pinero B, Pawliczak K, Makvand M, Najmabadi H; Genomics England Research Consortium, Maroofian R, Lester T, Yanez-Felix AL, Villarroel-Cortes CE, Xia F, Al Fayez K, Al Hashem A, Shears D, Irving M, Offiah AC, Kariminejad A, Taylor JC
Clin Genet 2023 Jul;104(1):121-126. Epub 2023 Mar 10 doi: 10.1111/cge.14324. PMID: 36896672Free PMC Article
Sajan SA, Ganesh J, Shinde DN, Powis Z, Scarano MI, Stone J, Winter S, Tang S
J Med Genet 2019 Dec;56(12):850-854. Epub 2018 Nov 26 doi: 10.1136/jmedgenet-2018-105639. PMID: 30478137

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