Fanconi Anemia: Examining Guidelines for Testing All Patients with Hand Anomalies Using a Machine Learning Approach

Background: This study investigated the questionable necessity of genetic testing for Fanconi anemia in children with hand anomalies. The current UK guidelines suggest that every child with radial ray dysplasia or a thumb anomaly should undergo further cost intensive investigation for Fanconi anemia. In this study we reviewed the numbers of patients and referral patterns, as well as the financial and service provision implications UK guidelines provide. Methods: Over three years, every patient with thumb or radial ray anomaly referred to our service was tested for Fanconi Anemia. CART Analysis and machine learning techniques using Waikato Environment for Knowledge Analysis were applied to evaluate single clinical features predicting Fanconi anemia. Results: Youden Index and Predictive Summary Index (PSI) scores suggested no clinical significance of hand anomalies associated with Fanconi anemia. CART Analysis and attribute evaluation with Waikato Environment for Knowledge Analysis (WEKA) showed no single feature predictive for Fanconi anemia. Furthermore, none of the positive Fanconi anemia patients in this study had an isolated upper limb anomaly without presenting other features of Fanconi anemia. Conclusion: As a conclusion, this study does not support Fanconi anemia testing for isolated hand abnormalities in the absence of other features associated with this blood disease.

Management of children’s hand disorders

Congenital hand anomalies form a broad spectrum of conditions. The assessment of the condition requires attention to the affected part as well as the child as a whole given the incidence of associated conditions. Congenital hand anomalies are classified according to the pattern and extent of the anomaly, and its aetiology. The most significant anomalies are described in this chapter with their individual classifications and options for treatment.

Chondrodysplasias With Multiple Dislocations Caused by Defects in Glycosaminoglycan Synthesis

Chondrodysplasias with multiple dislocations form a group of severe disorders characterized by joint laxity and multiple dislocations, severe short stature of pre- and post-natal onset, hand anomalies, and/or vertebral anomalies. The majority of chondrodysplasias with multiple dislocations have been associated with mutations in genes encoding glycosyltransferases, sulfotransferases, and transporters implicated in the synthesis or sulfation of glycosaminoglycans, long and unbranched polysaccharides composed of repeated disaccharide bond to protein core of proteoglycan. Glycosaminoglycan biosynthesis is a tightly regulated process that occurs mainly in the Golgi and that requires the coordinated action of numerous enzymes and transporters as well as an adequate Golgi environment. Any disturbances of this chain of reactions will lead to the incapacity of a cell to construct correct glycanic chains. This review focuses on genetic and glycobiological studies of chondrodysplasias with multiple dislocations associated with glycosaminoglycan biosynthesis defects and related animal models. Strong comprehension of the molecular mechanisms leading to those disorders, mostly through extensive phenotypic analyses of in vitro and/or in vivo models, is essential for the development of novel biomarkers for clinical screenings and innovative therapeutics for these diseases.

An unusual association of ulnar hemimelia with mesoaxial synostotic syndactyly

Ulnar hemimelia, also referred to as post-axial longitudinal deficiency of the upper limb, is a very rare skeletal anomaly characterized by the partial or complete absence of the ulna. The majority of the reported cases are sporadic and more common in males. The disorder is mostly unilateral, right-sided and incomplete. A slight shortening of the forearm, radial bowing and ulnar-sided hand drift are the anomalies which often accompany ulnar hemimelia. Ulnar hemimelia may also be seen in association with complex wrist and hand anomalies. The absence of post-axial metacarpal and digital bones are frequent findings in patients with this rare disorder. Cases with additional digital abnormalities such as post-axial syndactyly and camptodactyly are also present in the literature. However, a case of ulnar hemimelia in association with mesoaxial synostotic syndactyly has never been reported to date.

Appearance of Congenital Hand Anomalies

Background and Aims: Impact of appearance of congenital hand anomalies has not previously been reported. The purpose of this study was to describe the common perception about how different congenitally malformed hands look. Material and Methods: We developed a questionnaire in a game format to evaluate the appearance of different hands. Altogether 1450 (954 females) 4- to 84-year-old residents (296 children) of two European and one Asian (n = 102) country were asked to rate the appearance of different looking hands on a five-point pictorial Likert-type scale. Standardized photographs of the dorsal aspect of 17 different congenitally malformed non-operated hands and a normal hand were presented to respondents. Significance of age, gender, nationality, and profession of the respondents was assessed. Results: The respondents’ ranking order of the hands was nearly consistent. The normal hand (mean = 4.43, standard deviation = 0.85, Md = 5) and clinodactyly (mean = 4.37, standard deviation = 0.86, Md = 5) were perceived to have the best appearance. Symbrachydactyly (mean = 1.42, standard deviation = 0.68, Md = 1) and radial club hand (mean = 1.40, standard deviation = 0.68, Md = 1) received the lowest scores. Adults rated the appearance of hands higher than children regarding 14 hands, females higher than men regarding 15 hands, and Europeans higher than Asians in 4 hands (p < 0.05, respectively). Europeans rated four-finger hand (mean = 3.21, standard deviation = 1.18, Md = 3) better looking than six-finger hand (mean = 2.92, standard deviation = 1.18, Md = 3, p < 0.005), whereas Asians gave higher scores to six-finger hand (mean = 2.66, standard deviation = 1.26, Md = 3) compared to four-finger hand (mean = 2.51, standard deviation = 1.14, Md = 2). Medical doctors and nurses gave higher scores compared to the other profession groups, school children, and high school students in five hands (p < 0.05). Conclusion: A normal hand is perceived distinctly better looking than most congenitally different hands. Different malformations’ appearance was ranked very coherently in the same order despite of participants’ age, gender, nationality, or profession. Asians seem to prefer an additional digit to a four-finger hand.

Poland Syndrome with Atypical Malformations Associated to a de novo 1.5 Mb Xp22.31 Duplication

Poland's syndrome (PS; OMIM 173800) is a rare congenital syndrome which consists of absence or hypoplasia of the pectoralis muscle. Other features can be variably associated, including rib defects. On the affected side other features (such as of breast and nipple anomalies, lack of subcutaneous tissue and skin annexes, hand anomalies, visceral, and vertebral malformation) have been variably documented. To date, association of PS with central nervous system malformation has been rarely reported remaining poorly understood and characterized. We report a left-sided PS patient carrying a de novo 1.5 Mb Xp22.31 duplication diagnosed in addiction to strabismus, optic nerves and chiasm hypoplasia, corpus callosum abnormalities, ectopic neurohypophysis, pyelic ectasia, and neurodevelopmental delay. Since, to our knowledge, this features' association has not been previously reported, we argue that this case may contribute to further widening of the variability of PS phenotype.