Meromelia

Etiology

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 mothers with diabetes, 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.[1]

Epidemiology

Meromelia occurs in approximately 0.00001.4% of live births, as reported by Özdemir et al.[3] 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.[1]

History and Physical

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. They should also inquire about teratogenic exposures to drugs such as misoprostol or thalidomide, as these drugs have a known association with limb deformities. 

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.

Evaluation

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 are usually necessary to appropriately identify the anatomic deficiency. By appropriate understanding of each patient's anatomic abnormalities, appropriate treatment and prosthetics can be provided.

Treatment / Management

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.[4]

Differential Diagnosis

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.[1][4][5][6][7]

Prognosis

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.[1] 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.[4]

Complications

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.[8][9][10]