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Hypotrichosis-lymphedema-telangiectasia syndrome(HLTS)

MedGen UID:
375070
Concept ID:
C1843004
Disease or Syndrome
Synonym: HLTS
 
Gene (location): SOX18 (20q13.33)
 
Monarch Initiative: MONDO:0011914
OMIM®: 607823

Definition

Hypotrichosis-lymphedema-telangiectasia syndrome is an autosomal recessive disorder characterized by these 3 features, which begin at birth or in early childhood and are progressive (summary by Irrthum et al., 2003). [from OMIM]

Clinical features

From HPO
Hydrocele testis
MedGen UID:
318568
Concept ID:
C1720771
Congenital Abnormality
Accumulation of clear fluid in the between the layers of membrane (tunica vaginalis) surrounding the testis.
Predominantly lower limb lymphedema
MedGen UID:
320552
Concept ID:
C1835228
Finding
Localized fluid retention and tissue swelling caused by a compromised lymphatic system, affecting mainly the legs.
Palpebral edema
MedGen UID:
57877
Concept ID:
C0162285
Pathologic Function
Edema in the region of the eyelids.
Abnormality of the dentition
MedGen UID:
78084
Concept ID:
C0262444
Finding
Any abnormality of the teeth.
Absent eyebrow
MedGen UID:
98133
Concept ID:
C0431448
Congenital Abnormality
Absence of the eyebrow.
Sparse scalp hair
MedGen UID:
346499
Concept ID:
C1857042
Finding
Decreased number of hairs per unit area of skin of the scalp.
Alopecia
MedGen UID:
7982
Concept ID:
C0002170
Finding
A noncongenital process of hair loss, which may progress to partial or complete baldness.
Abnormal sweat gland morphology
MedGen UID:
892310
Concept ID:
C0262643
Anatomical Abnormality
Any structural abnormality of the sweat gland.
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.
Abnormal nail morphology
MedGen UID:
163115
Concept ID:
C0853087
Anatomical Abnormality
Abnormal structure or appearance of the nail.
Absent eyelashes
MedGen UID:
334299
Concept ID:
C1843005
Congenital Abnormality
Lack of eyelashes.
Palmar telangiectasia
MedGen UID:
866602
Concept ID:
C4020948
Anatomical Abnormality
The presence of telangiectases on the skin of palm of hand.
Non-immune hydrops fetalis
MedGen UID:
105327
Concept ID:
C0455988
Disease or Syndrome
Hydrops fetalis is a descriptive term for generalized edema of the fetus, with fluid accumulation in extravascular components and body cavities. It is not a diagnosis in itself, but a symptom and end-stage result of a wide variety of disorders. In the case of immune hydrops fetalis, a frequent cause is maternofetal incompatibility as in that related to a number of genetic anemias and metabolic disorders expressed in the fetus; in other instances, it remains idiopathic and likely multifactorial (summary by Bellini et al., 2009). Nonimmune hydrops fetalis accounts for 76 to 87% of all described cases of hydrops fetalis (Bellini et al., 2009). Genetic Heterogeneity of Hydrops Fetalis In southeast Asia, alpha-thalassemia (604131) is the most common cause of hydrops fetalis, accounting for 60 to 90% of cases. Almost all of these cases result from homozygous deletion of the HBA1 (141800) and HBA2 (141850) genes. A few cases have been reported that had 1 apparently normal alpha-globin gene, termed the hemoglobin H (613978) hydrops fetalis syndrome (summary by Chui and Waye, 1998). Other genetic disorders predisposing to NIHF include other congenital anemias, such as erythropoietic porphyria (e.g., 606938.0013), and many metabolic disorders, such as one form of Gaucher disease (e.g., 606463.0009), infantile sialic acid storage disease (269920), mucopolysaccharidosis type VII (253220), glycogen storage disease IV (232500), congenital disorder of glycosylation type Ia (212065), and disorders of lymphatic malformation (see, e.g., LMPHM1, 153100).

Recent clinical studies

Diagnosis

Wangberg H, Wigby K, Jones MC
Am J Med Genet A 2018 Dec;176(12):2824-2828. Epub 2018 Dec 14 doi: 10.1002/ajmg.a.40532. PMID: 30549413
Valenzuela I, Fernández-Alvarez P, Plaja A, Ariceta G, Sabaté-Rotés A, García-Arumí E, Vendrell T, Tizzano E
Eur J Med Genet 2018 May;61(5):269-272. Epub 2018 Jan 4 doi: 10.1016/j.ejmg.2018.01.001. PMID: 29307792
Wünnemann F, Kokta V, Leclerc S, Thibeault M, McCuaig C, Hatami A, Stheneur C, Grenier JC, Awadalla P, Mitchell GA, Andelfinger G, Preuss C
Can J Cardiol 2016 Jan;32(1):135.e1-7. Epub 2015 Apr 13 doi: 10.1016/j.cjca.2015.04.004. PMID: 26148450
Moalem S, Brouillard P, Kuypers D, Legius E, Harvey E, Taylor G, Francois M, Vikkula M, Chitayat D
Clin Genet 2015 Apr;87(4):378-82. Epub 2014 Apr 16 doi: 10.1111/cge.12388. PMID: 24697860
Glade C, van Steensel MA, Steijlen PM
Eur J Dermatol 2001 Nov-Dec;11(6):515-7. PMID: 11701398

Therapy

Overman J, Fontaine F, Wylie-Sears J, Moustaqil M, Huang L, Meurer M, Chiang IK, Lesieur E, Patel J, Zuegg J, Pasquier E, Sierecki E, Gambin Y, Hamdan M, Khosrotehrani K, Andelfinger G, Bischoff J, Francois M
Elife 2019 Jul 30;8 doi: 10.7554/eLife.43026. PMID: 31358114Free PMC Article

Prognosis

Wangberg H, Wigby K, Jones MC
Am J Med Genet A 2018 Dec;176(12):2824-2828. Epub 2018 Dec 14 doi: 10.1002/ajmg.a.40532. PMID: 30549413
Béri-Deixheimer M, Gregoire MJ, Toutain A, Brochet K, Briault S, Schaff JL, Leheup B, Jonveaux P
Eur J Hum Genet 2007 Apr;15(4):446-52. Epub 2007 Feb 7 doi: 10.1038/sj.ejhg.5201784. PMID: 17290276

Clinical prediction guides

Wangberg H, Wigby K, Jones MC
Am J Med Genet A 2018 Dec;176(12):2824-2828. Epub 2018 Dec 14 doi: 10.1002/ajmg.a.40532. PMID: 30549413
Downes M, François M, Ferguson C, Parton RG, Koopman P
Hum Mol Genet 2009 Aug 1;18(15):2839-50. Epub 2009 May 9 doi: 10.1093/hmg/ddp219. PMID: 19429912
Béri-Deixheimer M, Gregoire MJ, Toutain A, Brochet K, Briault S, Schaff JL, Leheup B, Jonveaux P
Eur J Hum Genet 2007 Apr;15(4):446-52. Epub 2007 Feb 7 doi: 10.1038/sj.ejhg.5201784. PMID: 17290276

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