Limb development is a complex regulated developmental phenomenon involving multiple genes (Ekbote, and Danda, 2012). Unilateral or bilateral fibular aplasia is a rare malformation, although the fibula is the most common long bone associated with a congenital absence (Courtens et al., 2005). Most cases of fibular aplasia are isolated and sporadic events, which implies that the majority are caused by nongenetic and teratogenic insults. However, fibular aplasia can be a part of a malformation syndrome when associated with focal deficiency of the proximal femur and distal digital and/or toe anomalies (femur fibula ulna syndrome, MIM 228200).
Fibular aplasia, tibial campomelia, and oligosyndactyly (FATCO) syndrome (MIM 246570) is a syndrome of unknown genetic basis and inheritance, with variable expressivity and penetrance. FATCO syndrome was first described by Hecht and Scott (1981). However, Courtens et al. (2005) proposed the acronym FATCO. Here, we report a new case with FATCO syndrome. To date, 12 cases have been published worldwide, excluding the case reported here (Hecht and Scott, 1981; Capece et al., 1994; Huber et al., 2003; Courtens et al., 2005; Kitaoka et al., 2009; Karaman and Kahveci, 2010; Vyskocil et al., 2011; Bieganski et al., 2012; Ekbote and Danda, 2012).
A boy was born at 35 weeks gestation by normal vaginal delivery. He was the third offspring of nonconsanguineous parents. His birth weight was 2755 g (above 50th centile), length was 44 cm (10th centile), and head circumference was 32 cm (50th centile). His Apgar scores were 2 and 6 at 1 and 5 min, respectively. There was no history of fever, trauma, rash, or teratogenic exposure during the antenatal period. On examination at birth, there was bilateral shortening of both legs, with anterior bowing associated with overlying skin dimpling over the junction of the proximal 2/3 and distal 1/3. He had right three-ray and left two-ray feet with oligosyndactyly (Figs 1 and 2). The upper limbs and the spine were normal. Systemic examination revealed no additional findings. The skeletal survey revealed bilateral fibular aplasia, bowed tibia (campomelia), oligosyndactyly, three metatarsals in the right foot, and two metatarsals in the left foot (Fig. 3). Femora, humeri, ulnae, and radii were normal. Chromosomal analysis and brain and pelvic abdominal ultrasound were normal. A diagnosis of FATCO syndrome was thus made.
The present case has features of FATCO syndrome, which consists of fibular aplasia, tibial campomelia, and oligosyndactyly. All reported 12 cases were characterized by sparing of the femora, pelvis, radii, and humerus. The unilateral/bilateral nature of involvement was almost equal (Karaman and Kahveci, 2010). The Online Mendelian Inheritance in Man (OMIM) database categorizes malformation syndromes with fibular aplasia into numerous entities, of which the following four disorders may have been considered in the differential diagnosis of this case: (a) orofaciodigital syndrome X, (b) fibular aplasia with ecterodactyly, (c) Fuhrmann syndrome, and (d) FATCO syndrome.
Orofaciodigital syndrome X (MIM 165590) presents fibular aplasia, along with radial, mesomelic shortening and facial dysmorphism with oral clefts and vestibular frenuli (Figuera et al., 1993). Fibular aplasia with ecterodactyly (MIM 113310) is reported to present with hypoplastic phalanges of the hands or feet, split hand/foot malformation, and fibular aplasia or hypoplasia.
Fuhrmann syndrome (MIM 228930), an autosomal recessive disorder, bears close resemblance to the FATCO syndrome but with a much wider spectrum, including aplasia/hypoplasia of the ulna, hypoplasia of the pelvis, aplasia/hypoplasia of the femur, fibular aplasia, and variable digital abnormalities, as well as absent or dysplastic nails. FATCO syndrome does not manifest pelvic, femoral, ulnar, or nail abnormalities. Moreover, a straight femur characterizes FATCO syndrome. The genetic cause of FATCO syndrome remains unknown. Hecht and Scott (1981) reported affected half sibs who shared a normal mother. The authors suggested recessive inheritance or gonadal mosaicism for a dominant mutation. Reports by Kitaoka et al. (2009) and Karaman and Kahveci (2010) excluded WNT7A as a potential gene for FATCO syndrome. Bieganski et al. (2012) documented three patients with FATCO syndrome. They performed genetic screening for copy-number variations and mutations in the TP63 and WNT10 B genes, which did not show any genetic abnormalities. The authors suggested that all FATCO patients belong to the phenotype fibular aplasia with ecterodactyly. However, this assumption needs identification of the molecular basis of FATCO syndrome.
We report the 13th case with FATCO syndrome, which is a rare genetic developmental limb disorder and, thus far, has an unknown molecular basis. Genetics counseling in these rare cases remains difficult.
Conflicts of interest
There are no conflicts of interest.
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