These 14 Peruvian patients represent 50% of the all patients reported worldwide to date [Hecht and Scott, 1981; Courtens et al., 2005; Kitaoka et al., 2009; Vyskocil et al., 2011; Ekbote and Danda, 2012; Bieganski et al., 2012; Goyal et al., 2014; Sezer et al., 2014; D’Amato Gutiérrez and Palacio Díaz, 2016; Abdalla and El-Beheiry, 2017; Isik et al., 2019; Önder Yılmaz et al., 2019; Izadi and Salehnia, 2020]. Abnormalities in the upper extremities were observed in 21.4% of the Peruvian patients, while previous reports mention that approximately two out of three show this anomaly (64.2%).
Early reports about this research state that the frequency of the total the number of anomalies was the same in both legs. The presence of dimples in the legs in this review prevailed in the right lower limb (35.7% vs. 21.4%) and in previous case reports show us in similar frequency [Hecht and Scott, 1981; Courtens et al., 2005; Kitaoka et al., 2009; Vyskocil et al., 2011; Ekbote and Danda, 2012; Bieganski et al., 2012; Goyal et al., 2014; Sezer et al., 2014; D’Amato Gutiérrez and Palacio Díaz, 2016; Abdalla and El-Beheiry, 2017; Isik et al., 2019; Önder Yılmaz et al., 2019; Izadi and Salehnia, 2020].
Regarding oligodactyly, in Peru, involvement of the fourth and fifth toes was more frequently observed, while in the previous reports, the frequency was higher in the fifth toe [Hecht and Scott, 1981; Courtens et al., 2005; Kitaoka et al., 2009; Vyskocil et al., 2011; Ekbote and Danda, 2012; Bieganski et al., 2012; Goyal et al., 2014; Sezer et al., 2014; D’Amato Gutiérrez and Palacio Díaz, 2016; Abdalla and El-Beheiry, 2017; Isik et al., 2019; Önder Yılmaz et al., 2019; Izadi and Salehnia, 2020] (Supplementary 2). Syndactyly of the first and second toes was poorly described in patients, but the right side was the only affected side in this and previous studies.
The absence of the fifth metatarsals and their respective phalanges prevailed in the right foot in the Peruvian patients, compared to previous reports where it predominated on the left side. Regarding the absence of the fourth metatarsal, its finding predominated in this report, presenting in 85.7%. However, in previous descriptions, it appears in 42.8% of the patients and the absence of the third metatarsal was not a significant finding in all reported cases.
In previous reports and in Peru, the presence of fibular aplasia was described as predominating in the right leg, which was associated in all patients with tibial campomelia.
Previous research show that the presence of tibial hypoplasia is described in 85.7% of all reported cases, with bilateral involvement in 28.6%, while in this study this clinical characteristic was observed in all patients without predominating over a particular side of the lower limbs.
Previously showed one patient with hypoplastic nails, but we do not observe the same in this cohort. In the same way, the screening of bone anomalies occurred in prior description and in relation to psychomotor development, it was not observed in Peruvian patients.
FATCO syndrome is an ultra-rare genetic disease, where one of its limitations is the lack of information about this pathology, such as etiology; even when we have a series of patient reports, they do not have certain variables necessary for a more accurate description. Another limitation found is based on the absence of molecular test, because don’t exist genomic variants related to FATCO syndrome, and there are also genetic diseases that share some of the clinical characteristics, but that could be differentiated through the use of diagnostic tools, such as the use of portals such as OMIN (On line Mendelian Inheritance in Man) or search programs such as Face2Gene, Phenomizer or Possum [Martinez-Monseny et al., 2019; Kohler et al., 2019]. However, this limitation does not affect the study, since it led us to reinforce the phenotypic detail of each patient. And finally, FATCO syndrome does not have a gold-standard test for diagnosis, which, if present, would facilitate diagnosis at any stage (prenatal and postnatal). It is necessary to consider the differential diagnoses that many of them have a genetic etiology identified through next generation sequencing [Warr et al., 2015; Levy and Myers, 2016] .
We have not been able to establish the reason why in Peru there would be a greater number of patients. However, there is a legend in the Peruvian jungle about the existence of a being called Chullachaqui, who has unequal lower limbs, the right large and the left small; so we deduce that this condition has been seen for a long time in this population [Arguedas and Ríos, 1970]. In this sense, it is necessary to carry out genomic studies such as massive sequencing or the use of microarrays with a greater number of markers in order to detect variants in a single nucleotide, multiple nucleotide or variants in the number of copies which will serve to establish not only the etiological molecular diagnosis; but, also, to recognize the processes of embryonic differentiation of the members, establish the risk of family and individual recurrence and propose future therapeutic improvements. If these studies were not conclusive, epigenetic studies would have to be carried out, as well as expression studies (transcriptome), among others.