Meromelia is defined broadly as the partial absence of at least one limb. Limb deficiencies have been known to be caused by chromosomal abnormalities, genetic disorders, environmental exposures in utero, or as a complication of chorionic villus sampling. While "amelia" refers to the complete absence of at least one limb, meromelia is just another form of the same continuum of the disorder based on severity.
In one study of congenital limb deficiencies, 64.8% of cases had an identifiable cause.
Of the 162 births with limb deformities that were considered, 13 (8.0%) were caused by chromosomal abnormalities. Trisomy 18 (Edward's Syndrome) was the most common, but also thrombocytopenia-absent radius (TAR) syndrome and trisomy 13 were observed.
14 (8.6%) of cases were caused by a known syndrome, association, sequence, or related anomaly. Vertebral defects, anal atresia, cardiac defects, tracheoesophageal fistula, renal anomalies, and limb abnormalities (VACTERL) association and anencephaly were most common in this category, while cloacal exstrophy, encephalocele, sirenomelia, prune belly syndrome, and urethral atresia were also noted.
A total of 16.1% of cases were attributed to Mendelian or familial inheritance. Ectrodactyly (i.e., cleft hand syndrome) was most common, but also Fanconi anemia, Holt-Oram syndrome, and many others were noted.
Teratogenic exposure to drugs accounted for 3.7% of cases in this study, with most resulting in infants of diabetic mothers, and one due to misoprostol exposure in utero. Take note, however, that thalidomide is classically associated with the truncation of limbs as phocomelia, and while not observed in this study is a well-known complication of the drug.
Vascular disruptions accounted for 28.4% of cases of limb defects and were most commonly caused by amniotic band syndrome. Poland syndrome and acardiac twins were other less common causes of limb deficiency.
The remaining 35.1% of limb deformities had an unknown cause.
Meromelia occurs in approximately 0.00001.4% of live births, as reported by Özdemir et al. In another review of 206,224 live births, 162 infants were identified with congenital limb deficiencies (0.079%). Of those, 101 children (62.3%) survived the first month of life. 53.7% of children with identified limb deficiencies were male, 39.5% were female, and the remainder were elective terminations where sex was not determined.
When a child is born with a truncated or deformed limb, practitioners should inquire about a family history of any possible inherited sources of limb deformity. One should also inquire about teratogenic exposures to drugs such as misoprostol or thalidomide, as these drugs have a known association with limb deformity.
Clinicians should perform a careful assessment for associated syndromes such as VACTERL anomalies or Fanconi anemia, which can have life-threatening consequences if left untreated. The anatomical variant will often help guide clinicians towards most likely associations, such as in the case of thrombocytopenia absent radius syndrome.
Genetic testing may be appropriate in the case of inherited disorders, or in cases of chromosomal abnormalities such as seen in Edwards syndrome (trisomy 18) or Patau syndrome (trisomy 13). Additionally, radiographs and vascular mapping of the truncated extremity is usually necessary to appropriately identify the anatomic deficiency. By appropriate understanding of each patient's anatomic abnormalities, appropriate treatment and prosthetics can be provided.
The most important management of a child born with a limb deficiency is to appropriately diagnose and treat any other associated abnormalities, particularly when they pertain to the heart, intestines, or other vital organs. Any time a congenital limb defect is noted, referral to pediatric cardiologists and gastroenterologists may be appropriate to treat any abnormalities that may be encountered.
From the perspective of a hypoplastic limb, prosthetics may be used to increase cosmesis and function, however, most people function quite well without prosthetics, even with severe limb truncation. Families of children with severely deformed extremities may benefit from physical and/or occupational therapy to meet the unique needs of patients.
Additionally, caring for a disabled child can be traumatic for some parents. Therefore, counseling and mental health services should be available to families and children as needed in the setting of deformity that causes a serious disruption in day to day life.
Over half of the cases of meromelia have a known association or underlying cause. Edward syndrome or trisomy 18 is the most common chromosomal abnormality associated with congenital limb defects. Similarly, a deletion on chromosome 1 can lead to thrombocytopenia absent-radius syndrome.
Ectrodactyly and Fanconi anemia are commonly inherited disorders associated with meromelia in children. Non-inherited associates such as VACTERL association frequently appear in conjunction with limb truncation deficits as well.
Gold et al. found that of 162 births with congenital limb deformities, 101 (or 62.3%) were liveborn and survived the first month of life, whereas 10 (or 6.2%) were liveborn but did not survive the first month, 17 (or 10.5%) were stillborn, and 34 (or 21%) were elective terminations. That being said, those who survive with limb truncation deformities typically have a high functional status, and generally, depending on the severity of their deformity can care for themselves very effectively with appropriate therapy and prosthetics.
Most life-threatening complications associated with limb truncation defects will be due to associated anomalies. For example, meromelia frequently presents in conjunction with VACTERL association, as discussed above, and the associated cardiovascular, intestinal, renal, and other congenital defects can result in a whole slew of complications. Those with Fanconi anemia have a high risk of aplastic anemia. TAR syndrome, as the name suggests, may also have hematologic consequences in the form of thrombocytopenia.
Increased drug regulatory practices may reduce the incidence of limb deformities associated with misoprostol and thalidomide. Additionally, uncontrolled diabetes may have a teratogenic effect, and therefore appropriate prenatal care and diabetes management may also have an effect on decreasing the number of limb deformities. Even in the setting of these teratogenic causes, meromelia is extremely rare, and many cases are unavoidable. Therefore, if a child is found to have a limb truncation defect, a thorough evaluation is necessary to optimize patient survival and management. Parents should have their child evaluated by an appropriate primary clinician, geneticist, cardiologist, nephrologist, and/or gastroenterologist depending on relevant associated conditions. Furthermore, physical and occupational therapy can play a substantial role in maximizing patient function.
Congenital limb defects can be devastating for parents, but many patients can have very functional, otherwise normal lives. As with any congenital deformity, appropriate care begins in the prenatal period. Appropriate obstetric care, prenatal screenings, and avoidance of teratogenic drugs is the first step to minimizing the risk of congenital deformity. For children with genetic or unknown causes of limb defects, an interprofessional team consisting of various specialists outlined previously in conjunction with appropriate therapists, nurses, and clinical staff must work together to identify risk factors for morbidity and mortality and effectively avoid complications. [Level 5]
|||Gold NB,Westgate MN,Holmes LB, Anatomic and etiological classification of congenital limb deficiencies. American journal of medical genetics. Part A. 2011 Jun; [PubMed PMID: 21557466]|
|||Smithells RW, Defects and disabilities of thalidomide children. British medical journal. 1973 Feb 3; [PubMed PMID: 4631040]|
|||Özdemir M,Kavak RP,Eraslan Ö, Upper Limb Meromelia with Oligodactyly and Brachymesophalangy of the Foot: An Unusual Association. Case reports in radiology. 2019; [PubMed PMID: 31341693]|
|||Davis DD,Kane SM, Cleft Hand (Ectrodactyly, Split Hand) 2020 Jan; [PubMed PMID: 32491739]|
|||Klopocki E,Schulze H,Strauss G,Ott CE,Hall J,Trotier F,Fleischhauer S,Greenhalgh L,Newbury-Ecob RA,Neumann LM,Habenicht R,König R,Seemanova E,Megarbane A,Ropers HH,Ullmann R,Horn D,Mundlos S, Complex inheritance pattern resembling autosomal recessive inheritance involving a microdeletion in thrombocytopenia-absent radius syndrome. American journal of human genetics. 2007 Feb; [PubMed PMID: 17236129]|
|||Genest DR,Di Salvo D,Rosenblatt MJ,Holmes LB, Terminal transverse limb defects with tethering and omphalocele in a 17 week fetus following first trimester misoprostol exposure. Clinical dysmorphology. 1999 Jan; [PubMed PMID: 10327252]|
|||Giampietro PF,Adler-Brecher B,Verlander PC,Pavlakis SG,Davis JG,Auerbach AD, The need for more accurate and timely diagnosis in Fanconi anemia: a report from the International Fanconi Anemia Registry. Pediatrics. 1993 Jun; [PubMed PMID: 8502512]|
|||Boussion S,Escande F,Jourdain AS,Smol T,Brunelle P,Duhamel C,Alembik Y,Attié-Bitach T,Baujat G,Bazin A,Bonnière M,Carassou P,Carles D,Devisme L,Goizet C,Goldenberg A,Grotto S,Guichet A,Jouk PS,Loeuillet L,Mechler C,Michot C,Pelluard F,Putoux A,Whalen S,Ghoumid J,Manouvrier-Hanu S,Petit F, TAR syndrome: Clinical and molecular characterization of a cohort of 26 patients and description of novel noncoding variants of RBM8A. Human mutation. 2020 Jul; [PubMed PMID: 32227665]|
|||Travessa AM,Dias P,Santos A,Custódio S,Sousa A,Sousa AB, Upper limb phocomelia: A prenatal case of thrombocytopenia-absent radius (TAR) syndrome illustrating the importance of chromosomal microarray in limb reduction defects. Taiwanese journal of obstetrics [PubMed PMID: 32127157]|
|||Al-Qattan MM, The Pathogenesis of Radial Ray Deficiency in Thrombocytopenia-Absent Radius (TAR) Syndrome. Journal of the College of Physicians and Surgeons--Pakistan : JCPSP. 2016 Nov; [PubMed PMID: 27981927]|