Makindo Medical Notes

The presence of limb defects depends on a critical 15-day period during early pregnancy when limb development occurs.

Aetiology

• Phocomelia limb atrophy is the most common malformation linked to thalidomide, although not all cases of phocomelia are caused by thalidomide.
• Thalidomide exposure generally does not cause harm if taken before day 34 or after day 50 following the last menstruation.
• The critical period for limb and organ development occurs between days 35 to 50 of pregnancy.

Clinical Features

• Phocomelia (limb reduction or absence).
• Absence of auricles, leading to deafness.
• Defects in the muscles of the eyes and face.
• Hypoplasia or absence of arms, particularly affecting the radius and thumb.
• Thumbs with three joints.
• Defects in the femur and tibia.
• Associated malformations of the heart, intestines, uterus, and gallbladder.

Investigations

• Genetic testing can help with differential diagnosis.
• An echocardiogram is recommended to detect associated heart defects.

Differentials

• Roberts-SC Phocomelia (Pseudothalidomide Syndrome): Autosomal recessive disorder with limb reduction deformities and associated cleft palate, malformed ears, limb reduction, and more.
• Holt-Oram Syndrome (Heart-Hand Syndrome): Autosomal dominant disorder affecting the hands and forearms, often associated with congenital heart defects.
• TAR Syndrome (Thrombocytopenia-Absent Radius): Autosomal recessive disorder characterized by thrombocytopenia and absent radii, with normal thumbs.
• Cornelia de Lange Syndrome: Limb defects, phocomelia, and other abnormalities including asymmetrical limb defects, proximal thumbs, and facial malformations.
• Fanconi's Panmyelopathy: Radial aplasia, short stature, hypoplasia of the thumb, and small testes, along with characteristic blood abnormalities.
• LADD Syndrome (Lacrimo-Auriculo-Dento-Digital Syndrome): Radial and external ear defects, often associated with hearing loss, cardiac, and dental abnormalities.
• Poland Anomaly (Poland Sequence): Unilateral hand defects associated with agenesis of part of the pectoralis major muscle and homolateral breast, nipple, or rib deficiency.
• FFU Syndrome (Femur-Fibula-Ulna): Limb defects primarily affecting the femur, fibula, and ulna, contrasting with thalidomide's tendency to affect the radius and humerus first.
• Goldenhar Syndrome (Oculo-Auriculo-Vertebral Dysplasia): Characterized by microtia, accessory auricles, cervical spine abnormalities, and facial asymmetry.
• Wildervanck Syndrome (Cervico-Oculo-Acoustic Syndrome): A condition predominantly affecting girls, characterized by malformed ears, deafness, and cervical spine defects.
• Moebius Syndrome: Characterized by facial and ocular palsies, most commonly occurring sporadically.
• Duane Syndrome: A disorder of ocular movement associated with limb and ear defects.
• VATER Association: A non-random association of vertebral defects, imperforate anus, and oesophageal atresia with tracheoesophageal fistula.
• Amniotic Band Syndrome: Characterized by ring constrictions and limb defects that resemble congenital amputations, often asymmetrical.

Management

• Multidisciplinary care involving genetics, orthopedics, and cardiology specialists is essential for managing associated limb, cardiac, and other organ defects.
• Surgical interventions may be necessary for limb reconstruction or correction of internal organ malformations.
• Physical therapy and occupational therapy are important for improving function and mobility in patients with limb defects.

References

• Thalidomide website Canada