Growth in achondroplasia including stature, weight, weight-for-height and head circumference from CLARITY: achondroplasia natural history study—a multi-center retrospective cohort study of achondroplasia in the US

Abstract Background Achondroplasia is the most common genetic skeletal disorder causing disproportionate short stature/dwarfism. Common additional features include spinal stenosis, midface retrusion, macrocephaly and a generalized spondylometaphyseal dysplasia which manifest as spinal cord compression, sleep disordered breathing, delayed motor skill acquisition and genu varus with musculoskeletal pain. To better understand the interactions and health outcomes of these potential complications, we embarked on a multi-center, natural history study entitled CLARITY (achondroplasia natural history study). One of the CLARITY objectives was to develop growth curves (length/height, weight, head circumference, weight-for-height) and corresponding reference tables of mean and standard deviations at 1 month increments from birth through 18 years for clinical use and research for achondroplasia patients. Methods All available retrospective anthropometry data including length/height, weight and head circumference from achondroplasia patients were collected at 4 US skeletal dysplasia centers (Johns Hopkins University, AI DuPont Hospital for Children, McGovern Medical School University of Texas Health, University of Wisconsin School of Medicine and Public Health). Weight-for-age values beyond 3 SD above the mean were excluded from the weight-for-height and weight-for-age curves to create a stricter tool for weight assessment in this population. Results Over 37,000 length/height, weight and head circumference measures from 1374 patients with achondroplasia from birth through 75 years of age were compiled in a REDCap database. Stature and weight data from birth through 18 years of age and head circumference from birth through 5 years of age were utilized to construct new length/height-for-age, weight-for-age, head circumference-for-age and weight-for-height curves. Conclusion Achondroplasia-specific growth curves are essential for clinical care of growing infants and children with this condition. In an effort to provide prescriptive, rather than purely descriptive, references for weight in this population, extreme weight values were omitted from the weight-for-age and weight-for-height curves. This well-phenotyped cohort may be studied with other global achondroplasia populations (e.g. Europe, Argentina, Australia, Japan) to gain further insight into environmental or ethnic influences on growth.

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Growth in Achondroplasia Including Stature, Weight, Weight-for-Height and Head Circumference from CLARITY: Achondroplasia Natural History Study— A Multi-Center Retrospective Cohort Study of Achondroplasia in the US

10.21203/rs.3.rs-743762/v1 ◽

2021 ◽

Author(s):

Julie Hoover-Fong ◽

Kerry J Schulze ◽

Adekemi Y Alade ◽

Michael B Bober ◽

Ethan Gough ◽

...

Keyword(s):

Natural History ◽

Skill Acquisition ◽

Head Circumference ◽

Clinical Care ◽

Growth Curves ◽

Cord Compression ◽

Natural History Study ◽

University Of Texas ◽

Texas Health ◽

Weight For Age

Abstract Background: Achondroplasia is the most common genetic skeletal disorder causing disproportionate short stature/dwarfism. Common additional features include spinal stenosis, midface retrusion, macrocephaly and a generalized spondylometaphyseal dysplasia which manifest as spinal cord compression, sleep disordered breathing, delayed motor skill acquisition and genu varus with musculoskeletal pain. To better understand the interactions and health outcomes of these potential complications, we embarked on a multi-center, natural history study entitled CLARITY (Achondroplasia Natural History Study). One of the CLARITY objectives was to develop growth curves (length/height, weight, head circumference, weight-for-height) and corresponding reference tables of mean and standard deviations at one month increments from birth through 18 years for clinical use and research for achondroplasia patients. Methods: All available retrospective anthropometry data including length/height, weight and head circumference from achondroplasia patients were collected at 4 US skeletal dysplasia centers (Johns Hopkins University, AI DuPont Hospital for Children, McGovern Medical School University of Texas Health, University of Wisconsin School of Medicine and Public Health). Weight-for-age values beyond 3 SD above the mean were excluded from the weight-for-height and weight-for-age curves to create a stricter tool for weight assessment in this population. Results: Over 37,000 length/height, weight and head circumference measures from 1,374 patients with achondroplasia from birth through 75 years of age were compiled in a REDCap database. Stature and weight data from birth through 18 years of age and head circumference from birth through 5 years of age were utilized to construct new length/height-for-age, weight-for-age, head circumference-for-age and weight-for-height curves. Conclusion: Achondroplasia-specific growth curves are essential for clinical care of growing infants and children with this condition. In an effort to provide prescriptive, rather than purely descriptive, references for weight in this population, extreme weight values were omitted from the weight-for-age and weight-for-height curves. This well-phenotyped cohort may be studied with other global achondroplasia populations (e.g. Europe, Argentina, Australia, Japan) to gain further insight into environmental or ethnic influences on growth.

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Achondroplasia Natural History Study (CLARITY): 60-year experience in cervicomedullary decompression in achondroplasia from four skeletal dysplasia centers

Journal of Neurosurgery Pediatrics ◽

10.3171/2020.12.peds20715 ◽

2021 ◽

pp. 1-7

Author(s):

Janet M. Legare ◽

Chengxin Liu ◽

Richard M. Pauli ◽

Adekemi Yewande Alade ◽

S. Shahrukh Hashmi ◽

...

Keyword(s):

Natural History ◽

Skeletal Dysplasia ◽

Natural History Study ◽

Entire Cohort ◽

University Of Texas ◽

Medical Diagnoses ◽

University Of Wisconsin ◽

Johns Hopkins University ◽

Texas Health ◽

Over Time

OBJECTIVE The authors sought to determine the overall incidence of cervicomedullary decompression (CMD) in patients with achondroplasia and the characteristics associated with those surgeries across multiple institutions with experience caring for individuals with skeletal dysplasias. METHODS Data from CLARITY (Achondroplasia Natural History Study) for 1374 patients with achondroplasia from four skeletal dysplasia centers (A. I. duPont Hospital for Children, Johns Hopkins University, University of Texas Health, and University of Wisconsin School of Medicine and Public Health) followed from 1957 to 2017 were recorded in a Research Electronic Data Capture (REDCap) database. Data collected and analyzed included surgeries, indications, complications, ages at time of procedures, screening procedures, and medical diagnoses. RESULTS There were 314 CMD procedures in 281 patients (20.5% of the entire cohort). The median age of first CMD was 1.3 years in males and 1.1 years in females. Over time, there was a decrease in the median age of patients at first CMD. All patients born before 1980 who underwent CMD had the procedure after 5 years of age, whereas 98% of patients born after 2010 underwent CMD before 5 years of age. In addition, a greater proportion of patients born in more recent decades had documented neuroimaging and polysomnography (PSG) prior to CMD. Ventriculoperitoneal shunts (VPSs) were placed more frequently in patients undergoing CMD (23%) than in the entire cohort (8%). Patients who required either CMD or VPS were 7 times more likely to require both surgeries than patients who required neither surgery (OR 7.0, 95% CI 4.66–10.53; p < 0.0001). Overall, 10.3% of patients who underwent CMD required a subsequent CMD. CONCLUSIONS The prevalence of CMD in this large achondroplasia cohort was 20%, with more recently treated patients undergoing first CMD at younger ages than earlier patients. The use of neuroimaging and PSG screening modalities increased over time, suggesting that increased and better surveillance contributed to earlier identification and intervention in patients with cervicomedullary stenosis and its complications.

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International retrospective natural history study of LMNA-related congenital muscular dystrophy

Brain Communications ◽

10.1093/braincomms/fcab075 ◽

2021 ◽

Author(s):

Rabah Ben Yaou ◽

Pomi Yun ◽

Ivana Dabaj ◽

Gina Norato ◽

Sandra Donkervoort ◽

...

Keyword(s):

Clinical Trial ◽

Muscular Dystrophy ◽

Natural History ◽

Early Onset ◽

Age Of Onset ◽

Clinical Care ◽

Common Mutation ◽

Natural History Study ◽

Cardiac Symptoms ◽

Independent Ambulation

Abstract Muscular dystrophies due to heterozygous pathogenic variants in LMNA gene cover a broad spectrum of clinical presentations and severity with an age of onset ranging from the neonatal period to adulthood. The natural history of these conditions is not well defined, particularly in patients with congenital or early onset who arguably present with the highest disease burden. Thus the definition of natural history endpoints along with clinically revelant outcome measures is essential to establishing both clinical care planning and clinical trial readiness for this patient group. We designed a large international cross-sectional retrospective natural history study of patients with genetically proven muscle laminopathy who presented with symptoms before two years of age intending to identify and characterize an optimal clinical trial cohort with pertinent motor, cardiac and respiratory endpoints. Quantitative statistics were used to evaluate associations between LMNA variants and distinct clinical events. The study included 151 patients (Median age at symptom onset 0.9 years, range: 0.0-2.0). Age of onset and age of death were significantly lower in patients who never aquired independent ambulation compared to patients who achieved independent ambulation. Most of the patients acquired independent ambulation (n = 101, 66.9%), and subsequently lost this ability (n = 86; 85%). The age of ambulation acquisition (Median: 1.2 years, range: 0.8-4.0) and age of ambulation loss (Median: 7 years, range 1.2-38.0) were significantly associated with the age of the first respiratory interventions and the first cardiac symptoms. Respiratory and gastrointestinal interventions occurred during first decade while cardiac interventions occurred later. Genotype-phenotype analysis showed that the most common mutation, p.Arg249Trp (20%), was significantly associated with a more severe disease course. This retrospective natural history study of early onset LMNA-related muscular dystrophy confirms the progressive nature of the disorder, initially involving motor symptoms prior to onset of other symptoms (respiratory, orthopedic, cardiac, and gastrointestinal). The study also identifies subgroups of patients with a range of long-term outcomes. Ambulatory status was an important mean of stratification along with the presence or absence of the p.Arg249Trp mutation. These categorizations will be important for future clinical trial cohorts. Finally, this study furthers our understanding of the progression of early onset LMNA-related muscular dystrophy and provides important insights into the anticipatory care needs of LMNA-related respiratory and cardiac manifestations.

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Home use of breast milk fortifier to promote postdischarge growth and breast feeding in preterm infants: a quality improvement project

Archives of Disease in Childhood ◽

10.1136/archdischild-2018-315951 ◽

2018 ◽

Vol 104 (10) ◽

pp. 1007-1012 ◽

Cited By ~ 2

Author(s):

Luise V Marino ◽

Carol Fudge ◽

Freya Pearson ◽

Mark John Johnson

Keyword(s):

Quality Improvement ◽

Breast Milk ◽

Preterm Infants ◽

Breast Feeding ◽

Head Circumference ◽

Clinical Care ◽

Population Group ◽

Improvement Project ◽

Retrospective Audit ◽

Weight For Age

To improve the postdischarge growth of exclusively breastfed preterm infants, born weighing ≤1.8 kg, by using breast milk fortifier (BMF) supplements postdischarge until 48 weeks’ gestational age. A quality improvement (QI) project involving plan–do–study–act (PDSA) cycles. A tertiary surgical neonatal unit. Preterm infants weighing ≤1.8 kg at birth. We completed four PDSA cycles to develop and improve an electronic patient information sheet to promote the use BMF beyond discharge. Safety, feasibility and attitudes of parents to home BMF were assessed using questionnaires. A retrospective audit (July 2015–September 2017) was completed investigating the effects of home BMF on growth up to 1 year of age. Change in SD scores for weight for age, length for age and head circumference of age at various time points compared with those at birth were calculated. Compared with baseline measurements (infants born October 2012–November 2013), the QI project resulted in improved growth (measured as the change in SD score from birth, cSDS) at discharge for weight (cSDS −0.7), head circumference (cSDS 0.4) and length (cSDS-0.8), and at 1 year for weight (cSDS 0.9) and length (cSDS 0.8). Home BMF appeared to be safe, and parents found its use acceptable. QI methods facilitated the successful integration of BMF into routine clinical care after discharge, improving the growth trajectory of exclusively breastfed preterm infants discharged home, as well as supporting breast feeding in this vulnerable population group.

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