American Journal of Medical Genetics Part A | 2019
Response to letter, broken bones, and irresponsible testimony: Enough is enough already: The flawed Ehlers–Danlos syndrome infant fragility theory should not rule
Abstract
To the Editor, It has come to our attention that across the country and around the world the flawed Ehlers–Danlos syndrome (EDS) infant bone fragility theory continues to be allowed by defense witnesses in civil and criminal proceedings in child abuse cases. Dr Colin Paterson places this theory into the correct historical context in his original letter published in this issue in this journal. In this response, a group of geneticists, radiologists, and child protection pediatricians outlines the reasons why this flawed theory should not be employed as a defense in the courtroom. The paradigm of flawed fracture theories is indeed called temporary brittle bone disease (TBBD) (Mendelson, 2005). This “diagnosis” was made in infants who presented with classic fractures highly suggestive of child abuse, including multiple rib fractures and classic metaphyseal lesions. The fractures were termed “temporary” because they ceased when the child was taken into protective custody. This TBBD theory has been repudiated by the AAP Committee on Child Abuse and Neglect (Jenny, 2006), and multiple professional societies (Mendelson, 2005; Servaes et al., 2016). It is important to distinguish TBBD from metabolic bone disease (MBD), a comorbidity in preterm, low birth weight, and chronically ill neonates estimated to occur in 16–40% of very low birth weight (<1,500 g) and extremely low birth weight (<1,000 g) infants. MBD is associated with decreased bone mineral content and fractures most commonly seen in the neonatal intensive care unit. Early nutritional intervention can reduce both the prevalence and the severity of osteopenia seen in MBD (Rehman & Narchi, 2015). TBBD, on the other hand, is characterized by multiple unexplained fractures commonly seen in term babies (Paterson & Monk, 2014). Dr Paterson was the leading proponent of TBBD, and he was “struck off” by the General Medical Counsel in England in 2004 for providing scientifically unfounded testimony in court (Dyer, 2004). Nonetheless, Dr Paterson continues to promote the TBBD concept, including the idea that infants with findings consistent with TBBD upon his examinations had, as he says, “at least one parent with a Beighton score of 4 or more, conventionally regarded as indicative of the hypermobility syndrome... We draw attention to the likely autosomal dominant inheritance of this risk factor for TBBD as well as the potential value of assessing parental joint laxity in evaluating children with fractures.” (Paterson & Mole, 2012). Paterson is actually describing joint hypermobility syndrome (JHS), and many people with hypermobile joints are asymptomatic. About 30% of the general population has a Beighton score of 4, so there is a 60% chance that one of two parents would have this score (Tinkle et al., 2017). Historically, the unsubstantiated EDS infant bone fragility theory has grown from the discredited root of TBBD. To explain further why the EDS infant bone fragility theory is false, it is necessary to review the background on EDS and its current diagnostic criteria, the distinction of EDS from osteogenesis imperfecta (OI), the principle that adult studies should not be extrapolated onto infants, and the idea that combining two flawed theories (EDS and low vitamin D) does not create one correct theory. In these cases, two wrongs do not make a right. There are actually 13 types of EDS, but the types alluded to in this flawed theory include primarily hypermobile EDS and classic EDS (cEDS), so this discussion focuses on those types. EDS most commonly comes to our medical attention in late childhood or early adulthood. Joint laxity, just one of the criteria for EDS, is often confirmed by a score of five or more on the 9-point Beighton score, a scale designed to assess children greater than 5 years of age and adults. However, flexibility in and of itself is not a genetic syndrome. Swimmers, dancers, gymnasts, and many people in the general population tend to be flexible. Athletes tend to be flexible. Every person has a flexible friend or relative who does party tricks. A clinical diagnosis of EDS does not rely on flexibility alone but also takes into account physical examination findings, a family history, and a history of chronic joint dislocations and pain (Malfait et al., 2017). Signs on physical examination may include soft, velvety, or stretchy skin, easy skin scarring, and stretch marks in unusual places. Fractures are not mentioned or even considered in the diagnostic criteria, because they are not a hallmark or characteristic of EDS (Levy, 2004; Tinkle et al., 2017; Castori et al., 2017). In the work-up for unexplained fractures, clinical evaluation and/or genetic testing for EDS are not indicated in infants or their parents (Byers et al., 2006; Christian & Committee on Child Abuse and Neglect, 2015; Pepin & Byers, 2015). EDS differs from OI, which is commonly known as brittle bone disease. OI is a connective tissue disorder that can be associated with fractures, but with careful medical work-up, and review of clinical history, laboratory data, family history, physical examination, and radiological evidence, OI can be differentiated from child abuse (Pereira, 2015; Greely & Donaruma-Kwoh, 2015; Zarate et al., 2016). In the work-up of unexplained fractures, ruling out OI and consideration of genetic testing, when appropriate, is the standard of care (Byers et al., Received: 3 July 2019 Accepted: 12 August 2019