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Tetraamelia syndrome 2(TETAMS2)

MedGen UID:
1648284
Concept ID:
C4747923
Disease or Syndrome
Synonym: TETRAAMELIA SYNDROME 2 WITH PULMONARY AGENESIS
 
Gene (location): RSPO2 (8q23.1)
 
Monarch Initiative: MONDO:0060732
OMIM®: 618021

Definition

Tetraamelia syndrome-2 (TETAMS2) is characterized by rudimentary appendages or complete absence of the limbs, usually symmetric, as well as bilateral agenesis of the lungs. There are abnormalities of the pulmonary vasculature and dysmorphic features, including bilateral cleft lip/palate, ankyloglossia, mandibular hypoplasia, microretrognathia, and labioscrotal fold aplasia (Szenker-Ravi et al., 2018). For a discussion of genetic heterogeneity of TETAMS, see 273395. [from OMIM]

Additional description

From MedlinePlus Genetics


Tetra-amelia syndrome type 2 is usually characterized by complete absence of both lungs. Affected individuals often have heart abnormalities, such as defects in the walls between the chambers of the heart (septal defects) or absence of the mitral valve, which connects the two left chambers of the heart. People with type 2 can also have facial abnormalities that include partial or complete fusion of the upper and lower eyelids, the bottom of the tongue attached to the floor of the mouth, or a small lower jaw (micrognathia).

Tetra-amelia syndrome type 1 is typically characterized by severe gastrointestinal problems. These problems include an opening in the abdomen through which various abdominal organs can protrude(abdominal wall defect), abnormalities in the muscle (diaphragm) that separates the organs in the abdomen from those in the chest, and lack of an anal opening (imperforate anus). People with type 1 also tend to have frequent urinary tract problems, such as a lack of kidney development (renal agenesis). 

There are two forms of tetra-amelia syndrome that have been described, and while the features overlap, they are distinguished by their signs and symptoms and genetic cause. 

This syndrome can also cause severe malformations of other parts of the body, including the nervous system, face, head, heart, skeleton, gastrointestinal system, urinary tract, and genitalia. The lungs are underdeveloped in many cases, which makes breathing difficult or impossible. Because children with tetra-amelia syndrome have such serious medical problems, most are stillborn or die shortly after birth. 

Tetra-amelia syndrome (sometimes known as TETAMS) is a very rare disorder characterized by the absence of all four limbs. ("Tetra" is the Greek word for "four," and "amelia" refers to the failure of an arm or leg to develop before birth.)    https://medlineplus.gov/genetics/condition/tetra-amelia-syndrome

Clinical features

From HPO
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.
Amelia
MedGen UID:
8014
Concept ID:
C0002447
Congenital Abnormality
Congenital absence (aplasia) of one or more limbs.
Ventricular septal defect
MedGen UID:
42366
Concept ID:
C0018818
Congenital Abnormality
A hole between the two bottom chambers (ventricles) of the heart. The defect is centered around the most superior aspect of the ventricular septum.
Hypoplastic pulmonary veins
MedGen UID:
373427
Concept ID:
C1970501
Finding
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.
Micrognathia
MedGen UID:
44428
Concept ID:
C0025990
Congenital Abnormality
Developmental hypoplasia of the mandible.
Microretrognathia
MedGen UID:
326907
Concept ID:
C1839546
Finding
A form of developmental hypoplasia of the mandible in which the mandible is mislocalised posteriorly.
Bilateral lung agenesis
MedGen UID:
867250
Concept ID:
C4021610
Congenital Abnormality
Bilateral lack of development of the lungs.
Ankyloglossia
MedGen UID:
56288
Concept ID:
C0152415
Congenital Abnormality
Ankyloglossia, commonly known as 'tongue-tie,' is a congenital anomaly that occurs predominantly in males and is characterized by an abnormally short lingual frenulum. The phenotype varies from absence of clinical significance to rare complete ankyloglossia where the ventral part of the tongue is fused to the floor of the mouth (Klockars, 2007). Some patients also exhibit absence of lower incisors (Acevedo et al., 2010).
Glossoptosis
MedGen UID:
78623
Concept ID:
C0267048
Disease or Syndrome
Posterior displacement of the tongue into the pharynx, i.e., a tongue that is mislocalised posteriorly.
Bilateral cleft lip
MedGen UID:
451046
Concept ID:
C0392005
Congenital Abnormality
A non-midline cleft of the upper lip on the left and right sides.
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).
Absent nipple
MedGen UID:
64223
Concept ID:
C0175755
Congenital Abnormality
Congenital failure to develop, and absence of, the nipple.
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).

Recent clinical studies

Diagnosis

de Ravel TJ, Seftel MD, Wright CA
Am J Med Genet 1997 Jan 20;68(2):185-9. doi: 10.1002/(sici)1096-8628(19970120)68:2<185::aid-ajmg13>3.0.co;2-q. PMID: 9028456
Rosenak D, Ariel I, Arnon J, Diamant YZ, Ben Chetrit A, Nadjari M, Zilberman R, Yaffe H, Cohen T, Ornoy A
Am J Med Genet 1991 Jan;38(1):25-8. doi: 10.1002/ajmg.1320380107. PMID: 2012129

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