The presence of limb defects depends on a 15 day period when limb development is happening
- Phocomelia limb atrophy is the most common malformation linked to thalidomide, but all phocomelia cases aren't caused by thalidomide
- Generally, thalidomide do not have any consequences if taken before the 34th or after the 50th day following the last menstruation.
- The period that goes from the 35th to the 50th day of pregnancy is critical
- It is during that time that the fetus develops its limbs and organs
- Absence of the auricles with deafness.
- Defects of the muscles of the eye and of the face.
- Absence or hypoplasia of arms, preferentially affecting the radius and the thumb.
- Thumbs with three joints.
- Defects of the femur and of the tibia.
- Malformations of the heart, the bowel, the uterus, and the gallbladder
- Genetics may help with differentials
- Roberts-SC Phocomelia (Pseudothalidomide syndrome, Roberts syndrome, SC syndrome) is an autosomal recessive disorder that includes limb reduction deformities. Some abnormalities associated with this syndrome include but are not limited to cleft palate, malformed ears with hypoplastic lobules, various degrees of limb reduction, reduction in numbers or length of fingers and/or toes.
- Holt-Oram Syndrome also known as Heart Hand syndrome is an autosomal dominant disorder usually affecting the hands and forearms symmetrically, and associated in almost all cases with congenital heart disease, principally atrial septal defect. Some of the abnormalities noted with this syndrome include but are not limited to: phocomelia, all gradations of the defect in the upper limb and shoulder girdle, and the thumbs may be absent, hypoplastic, triphalangeal, or bifid.
- TAR Syndrome (thrombocytopenia-absent radius) is an autosomal recessive disorder in which thrombocytopenia tends to improve and may not be evident after the neonatal period, and in which absent radii (bilateral) are associated with normal thumbs. Abnormalities in the legs are reported in 50% of the cases.
- Cornelia de Lange Syndrome is a syndrome in which the limb defects are asymmetrical. Some other abnormalities associated with this syndrome include but are not limited to: phocomelia and oligodactyly, proximal implantation of thumbs, depressed nasal bridge, and undescended testes.
- Fanconi's Panmyelopathy includes radial aplasia as a feature, but the blood changes indicate the diagnosis. Some of the abnormalities associated with this condition include but are not limited to: short stature, hypoplasia to aplasia of thumb, small penis, and small testes.
- LADD Syndrome or lacrimo-auriculo-dento-digital syndrome results in radial and external ear defects which may be associated with deafness, eye, cardiac, and dental defects. Limb abnormalities that can be associated with this syndrome include but are not limited to digitalization of thumb (95%), triphalangeal thumb, syndactyly between the index and middle fingers, absent radius and thumb, and shortening of radius and ulna.
- Poland Anomaly (Poland Sequence) is unilateral with the hand defect being associated with agenesis of part of the pectoralis major muscle. There may be homolateral deficiency of the breast, nipple, or ribs. It is estimated that 10% of patients with syndactyly of the hand have Poland sequence, and it is 75% right-sided.
- FFU Syndrome (femur-fibula-ulna) is a syndrome in which the named bones are principally affected, contrasting with thalidomide which affects the radius and humerus before the ulna, and the tibia before the fibula. The defects may be very asymmetrical.
- Goldenhar Syndrome (oculo-auriculo-vertebral dysplasia), which merges with hemifacial microsomia, is characterised by microtia, accessory auricles, epibulbar dermoids, and abnormalities of the cervical spine. When unilateral this syndrome tends to be right-sided. Other abnormalities that are associated with this syndrome include but are not limited to middle ear anomaly with variable deafness, cleft lip, and cleft palate.
- Wildervanck Syndrome (cervico-oculo-acoustic syndrome) is seen predominantly in girls and is characterised by malformed ears, deafness, and defects of the cervical spine. Thalidomide rarely affects the cervical spine. Cleft palate has also been identified as an occasional abnormality associated with this syndrome.
- Moebius Syndrome (Moebius sequence) may manifest as facial/ocular palsies. It is most commonly a sporadic occurrence in an otherwise normal family.
- Duane Syndrome is a disorder of ocular movements characterised by (1) decreased abduction, (2) decreased adduction, (3) retraction of the globe on adduction, (4) oblique rise or depression on adduction, (5) partial closure of the eyelids on adduction, (6) deficient convergence. It may be bilateral or unilateral. An association with other defects, especially of the hands and ears, was described as long ago as 1918.
- Vater Association, a non-random association of vertebral defects, imperforate anus, and oesophagal atresia with tracheoesophageal fistula has long been appreciated.
Some other abnormalities or defects include but are not limited to: thumb or radial hypoplasia, and defects of the lower limb (23%).
- Amniotic Band Lesions most often affect a single limb, are rarely symmetrical, and resemble "congenital amputations". Ring constrictions may be present on one or more limbs. Amniotic band disruption sequence syndrome also has cleft lip and palate listed as an abnormality that can be associated with it. Failure to understand the cause of this condition can lead to misdiagnosis and inappropriate family and genetic counselling.