RESUMO
BACKGROUND: Koolen-de Vries (KdV) syndrome is caused by a 17q21.31 deletion leading to clinical symptoms of hypotonia and developmental delay and can present with abnormal hair texture. Menkes disease is an X-linked recessive inherited disease caused by pathogenic variants in ATP7A, which leads to profound copper deficiency. METHOD: We identified an infant male who presented with prematurity, hypotonia, and dysmorphic features for whom a family history of clinical Menkes disease was revealed after discussion with the clinical genetics team. RESULTS: Although initial first-tier genetic testing identified Kdv syndrome (17q21.31 syndrome), the family history led the team to consider a second diagnostic possibility, and testing of ATP7A revealed a pathogenic variant (c.601C>T, p.R201X). CONCLUSION: Menkes disease and KdV syndrome may both present with hypotonia and abnormal hair, in addition to seizures and failure to thrive. While these genetic conditions have overlapping clinical features, they have different natural histories and different therapeutic options. Here, we report on a patient affected with both disorders and review the diagnostic and therapeutic difficulties this presented.
Assuntos
Anormalidades Múltiplas/genética , ATPases Transportadoras de Cobre/genética , Deficiência Intelectual/genética , Síndrome dos Cabelos Torcidos/genética , Anormalidades Múltiplas/diagnóstico , Deleção Cromossômica , Cromossomos Humanos Par 17/genética , Hibridização Genômica Comparativa , Análise Mutacional de DNA , Evolução Fatal , Testes Genéticos , Histidina/análogos & derivados , Histidina/uso terapêutico , Humanos , Hipertensão Pulmonar/complicações , Hipertensão Pulmonar/genética , Hipertensão Pulmonar/terapia , Recém-Nascido , Deficiência Intelectual/complicações , Deficiência Intelectual/diagnóstico , Masculino , Anamnese , Síndrome dos Cabelos Torcidos/complicações , Síndrome dos Cabelos Torcidos/diagnóstico , Síndrome dos Cabelos Torcidos/tratamento farmacológico , Mutação , Óxido Nítrico/uso terapêutico , Compostos Organometálicos/uso terapêutico , Linhagem , Insuficiência Respiratória/genéticaRESUMO
BACKGROUND: Many extremely preterm infants have low vitamin D concentrations at birth, but early childhood outcomes after vitamin D supplementation have not been reported. OBJECTIVE: To determine a dose-response relationship between increasing doses of enteral vitamin D in the first 28 days after birth and cognitive scores at 2 years of age. METHODS: In this phase II double-blind dose-response randomized trial, infants with gestational ages between 23 and 27 weeks were randomly assigned to receive placebo or a vitamin D dose of 200 or 800 IU/day from day 1 of enteral feeding to postnatal day 28. The primary outcome of this follow-up study was Bayley III cognitive score at 22-26 months of age. RESULTS: Seventy of 80 survivors had a follow-up evaluation at 2 years of age (88%). There were no significant differences in cognitive scores between supplementation groups (p = 0.47). Cognitive scores did not differ between the higher vitamin D dose group and the placebo group (median difference favoring the 800 IU group: +5 points; 95% CI: -5 to 15; p = 0.23). The linear trend between increasing doses of vitamin D and reduction of neurodevelopmental impairment (placebo group: 54%; 200 IU group: 43%; 800 IU group: 30%; p = 0.08) or language impairment (placebo group: 64%; 200 IU group: 57%; 800 IU group: 45%; p = 0.15) was not statistically significant. Respiratory outcomes at 2 years of age (need for supplemental oxygen or asthma medications) did not differ between groups. CONCLUSION: In extremely preterm infants, early vitamin D supplementation did not significantly improve cognitive scores. Though underpowered for clinically meaningful differences in early childhood outcomes, this trial may help determine dosing for further investigation of vitamin D supplementation.