Each month, this department features a discussion of an unusual diagnosis. A description and images are presented, followed by the diagnosis and an explanation of how the diagnosis was determined. As always, your comments are welcome via email at pedann@Healio.com.
An infant was born by cesarean section at 35 weeks of gestational age to a 37-year-old G13P8 woman with a history of insulin-dependent diabetes who had no prenatal care. Apgar scores at birth were 8 at 1 minute and 9 at 5 minutes, and he weighed 3,130 g (90th percentile for gestational age). The neonatologist was consulted soon after birth due to the child’s respiratory distress. On physical examination, he was crying and vigorous with normal heart rate and rhythm, and no murmur. He had a three-vessel umbilical cord and normal bilateral upper extremities. No movements were visible on the lower extremities. He had bilateral hip abduction, his ankles showed equinovarus deformity, and he had fixed bilateral knee extension (Figure 1). Passive movements were extremely limited, but his pain sensation was intact. His spine appeared to be straight, with flattening of the gluteal region.
A neonate presenting with hips abduction and multiple lower extremities deformities.
A laboratory test on admission for methamphetamine was positive for both the mother and infant. The mother’s hemoglobin A1C was 8.5%. The patient was placed on nasal continuous positive airway pressure for respiratory support. He had persistent hypoglycemia requiring high dextrose, calcium, and steroid infusion. He was also noted to have incontinence of his bowel and urinary system with skin excoriation. Imaging studies were obtained and confirmed the diagnosis.
Caudal Regression Syndrome with Arthrogryposis of the Lower Extremities
Radiographs of the lower extremities and thoracic and lumbar spine showed hypoplastic L3, and agenesis of L4 and L5 with complete absence of the sacrum (Figure 2 and Figure 3). Spinal ultrasound showed bulbous appearance of the cord. Spinal magnetic resonance imaging showed severe truncation of the sacrum with bilateral hypoplastic iliac wings (Figure 4). An ultrasound of the hips showed bilateral hip dislocation. He had fixed joint contractures in bilateral ankles and knees, confirming the diagnosis of arthrogryposis.
Radiograph showing hypoplastic lumbar and absence of the sacrum.
Radiograph showing multiple deformities involving the sacrum and lower extremities.
Magnetic resonance imaging showing truncation of the sacrum.
Differential diagnoses for this infant are sirenomelia and Currarino syndrome. Sirenomelia is a rare disorder, also known as “mermaid syndrome,” in which the lower extremities are fused or partially fused together. It is also associated with abnormal development of the genitourinary tract, kidneys, lumbosacral spine, and gastrointestinal tract system. Currarino syndrome is an inherited disorder of abnormal sacral development with anorectal malformation and presence of presacral mass.
Caudal regression syndrome (CRS) or sacral agenesis is a rare disorder that is characterized by absence of the entire sacrum and variable lumbar involvement. It can be associated with abnormalities of the urogenital and gastrointestinal system. Affected musculoskeletal and neural defects include foot deformities, knees flexion contracture with popliteal webbing, hip flexion contractures, hip dislocation, spino-pelvic instability, and scoliosis.1,2 Typically, patients have normal cognitive development and hypoplastic limbs with flexion contractures of the ankles, knees, and hips forming a “Buddha-like” position.1 The syndrome was first described by Duhamel in 1961, when he encountered infants with sirenomelia and considered it to be an extreme case of CRS.3
Its incidence is about 1 in every 100,000 pregnancies but it occurs in up to 1% of pregnancies of women with diabetes prior to pregnancy. Women with insulin-dependent diabetes are 200 to 400 more times more likely to have a child with CRS than normal healthy women. In most cases, it occurs sporadically.4 Experimental studies have also suggested that hyperglycemia is a teratogen in between the third and seventh week of gestation, when organogenesis is initiated.5
The development of the axial skeleton begins on the 15th day of intrauterine life. Cells that divide from the primitive streak form the notochord, which elongates toward the cephalic aspect of the embryo. Both the notochord and neural plate develop in parallel, and they are completed by the 20th day. The notochord stimulates the paraxial mesoderm to condense and form somites, and within the somites the sclerotomes are formed. The sclerotomes eventually become vertebral bodies. Failure for the sclerotomes to appear at particular levels results in agenesis of the lumbosacral spine, so the motor nerves are not subsequently induced. The dorsal portion of the spinal cord continues to develop, which results in intact sensation because they have been derived from the neural crest cells.1
Along with agenesis of the sacrum, urinary incontinence frequently occurs in patients with CRS. Voiding impairment due to flaccid neurogenic bladder, vesiculoureteral reflux, and recurrent urinary tract infections contributes to renal damage.6 Other defects include lack of anal sphincter control, poor intestinal peristalsis, renal agenesis, and, in some cases, cardiovascular and respiratory complications.
CRS is classified by Renshaw7 into four types: type I—either partial or total unilateral sacral agenesis; type II—partial sacral agenesis with partial but bilaterally symmetrical defect, and stable articulation between the ilia and normal or hypoplastic S1 vertebra; type III—variable lumbar and total sacral agenesis with ilia articulating, with the sides of the lowest vertebra present; and type IV—variable lumbar and total sacral agenesis with caudal endplate of the lowest vertebra resting above either fused ilia or an iliac amphiarthrosis. The types correlate with motor functional abilities that can range from being asymptomatic to severe deformities of the pelvis and lower extremities. In patients with severe forms, the skeletal muscles in the lower extremities are replaced with fat due to extreme neuronal atrophy that results in defective innervation of the musculatures.1
Severe deformities of the lower extremities could lead to arthrogryposis, a term used to describe multiple congenital contractures that occur in two or more areas of the body. It is a clinical finding that is related to more than 300 disorders. In this instance, the infant had abnormal neurological function of the lower extremities secondary to the lack of motor function, which led to decreased movement in-utero and subsequent akinesia. The most common isolated congenital contracture is clubfoot, which only affects one area of the body. The differential diagnosis in a child with normal neurological function with arthrogryposis would include amyoplasia, generalized connective tissue disorder, or fetal crowding.8
Management of CRS is best accomplished with a multidisciplinary approach. Due to the devastating consequences of this disease in the urinary tract, timely diagnosis, thorough evaluation, and appropriate intervention are essential.6 Approach to orthopedic treatment is individualized. The conservative approach includes bracing, whereas surgical release or amputation/osteotomy and disarticulation are determined by the degree in which the deformities contribute to postural difficulties or restriction of mobility. Patients with type III and type IV CRS must also be observed closely for signs of progressive kyphosis.1
CRS is a rare, irreversible disorder that can affect other organ systems and have great effect on the quality of life. Its management includes a multidisciplinary approach by an orthopedic surgeon, a neurosurgeon, a physical and occupational therapist, a urologist, and a pediatrician. The surgical approach to manage the deformities of the lower extremities is controversial, especially when it involves patients with type III and type IV CRS. Patients with CRS are best managed on a case-by-case basis because they have a variety of clinical presentations. If they are trying to conceive, women with diabetes should have strict glycemic control and be monitored closely because they are at increased risk of having infants with this disorder.
- Altaf F, Hakel W, Sivaraman A, Noordeen H. Orthopaedic management of caudal regression syndrome. Eur J Orthop Surg Traumatol. 2008;18:531–535. doi:10.1007/s00590-008-0347-0 [CrossRef]
- Canale ST, Beaty JH. Campbell’s Operative Orthopaedics. 12th ed. Philadelphia, PA: Elsevier; 2013:1865.
- Duhamel B. From the mermaid to anal imperforation: the syndrome of caudal regression. Arch Disabled Child. 1961;36(186):152–155. doi:10.1136/adc.36.186.152 [CrossRef]
- Boulas MM. Recognition of caudal regression syndrome. Adv Neonatal Care. 2009;9:61–69. doi:10.1097/ANC.0b013e31819de44f [CrossRef]
- Allen VM, Armson BA, Wilson RD, et al. Teratogenicity associated with pre-existing and gestational diabetes. J Obstet Gynaecol Can. 2007;29:927–944.
- Emami-Naeini P, Nejat F, Rahbar Z, Kajbafzadeh A, El Khashab M. Urological manifestations of sacral agenesis. J Pediatr Urol. 2012;8(2):181–186. doi:10.1016/j.jpurol.2011.02.004 [CrossRef]
- Renshaw TS. Sacral agenesis. J Bone Joint Surg. 1978;60:373–383.
- Bamshad M, Van Heest AE, Pleasure D. Arthrogryposis: a review and update. J Bone Joint Surg Am. 2009;13(Suppl 4):40–46. doi:10.2106/JBJS.I.00281 [CrossRef]