BACKGROUND: Maternal uniparental disomy for chromosome 6 (upd(Cajaiba MM, Witchel S, Madan-Khetarpal S, Hoover J, Hoffner L, Macpherson T, et al. Prenatal diagnosis of trisomy 6 rescue resulting in paternal UPD6 with novel placental findings. Am J Med Genet Part A. 2011;155 A(8):1996-2002.)mat) has been previously reported to cause intrauterine growth restriction (IUGR), but the specific clinical phenotype has not been defined. Based on clinical data from two new cases and patients from the literature, specific phenotypes and mechanisms will be discussed further.
METHODS: In case 1, a maternal isodisomy mixed with a heterodisomy was found on chromosome 6, including a regional absence of heterozygosity between 6q23.3 and 6q27. In case 2, a homozygous SCUBE3 mutation and upd(Cajaiba MM, Witchel S, Madan-Khetarpal S, Hoover J, Hoffner L, Macpherson T, et al. Prenatal diagnosis of trisomy 6 rescue resulting in paternal UPD6 with novel placental findings. Am J Med Genet Part A. 2011;155 A(8):1996-2002.)mat, involving the 6p21.1-25.1 region were found. Clinical data related to upd(Cajaiba MM, Witchel S, Madan-Khetarpal S, Hoover J, Hoffner L, Macpherson T, et al. Prenatal diagnosis of trisomy 6 rescue resulting in paternal UPD6 with novel placental findings. Am J Med Genet Part A. 2011;155 A(8):1996-2002.)mat were also reviewed. Of all the 21 reported cases with upd(Cajaiba MM, Witchel S, Madan-Khetarpal S, Hoover J, Hoffner L, Macpherson T, et al. Prenatal diagnosis of trisomy 6 rescue resulting in paternal UPD6 with novel placental findings. Am J Med Genet Part A. 2011;155 A(8):1996-2002.)mat (including our 2 cases), 18 (85.7%) presented IUGR.
CONCLUSIONS: The phenotypes of the two newly identified patients with upd(Cajaiba MM, Witchel S, Madan-Khetarpal S, Hoover J, Hoffner L, Macpherson T, et al. Prenatal diagnosis of trisomy 6 rescue resulting in paternal UPD6 with novel placental findings. Am J Med Genet Part A. 2011;155 A(8):1996-2002.)mat further suggest that IUGR is associated with upd(Cajaiba MM, Witchel S, Madan-Khetarpal S, Hoover J, Hoffner L, Macpherson T, et al. Prenatal diagnosis of trisomy 6 rescue resulting in paternal UPD6 with novel placental findings. Am J Med Genet Part A. 2011;155 A(8):1996-2002.)mat and case 2 is the first reported upd(Cajaiba MM, Witchel S, Madan-Khetarpal S, Hoover J, Hoffner L, Macpherson T, et al. Prenatal diagnosis of trisomy 6 rescue resulting in paternal UPD6 with novel placental findings. Am J Med Genet Part A. 2011;155 A(8):1996-2002.)mat patient with a homozygous SCUBE3 gene mutation. However, the specific phenotypes involved in upd(Cajaiba MM, Witchel S, Madan-Khetarpal S, Hoover J, Hoffner L, Macpherson T, et al. Prenatal diagnosis of trisomy 6 rescue resulting in paternal UPD6 with novel placental findings. Am J Med Genet Part A. 2011;155 A(8):1996-2002.)mat and the related mechanisms need to be further studied.

UNASSIGNED: The prevalence and risk factors for failure to thrive (FTT) in pediatric patients with congenital heart disease (CHD) remain ambiguous. We aimed to investigate the prevalence, growth profiles, risk factors, and vulnerable subtypes of CHD associated with FTT in pediatric patients with CHD.
UNASSIGNED: This was a cross-sectional study based on Chinese Database for Congenital Heart Surgery. FTT was defined as either stunting or underweight (height or weight standard deviation score <-2), and they were standardized by references of normal Chinese population. Risk factors was determined with logistic regression model, and growth profiles were delineated in each subgroup.
UNASSIGNED: A total of 13,256 CHD patients were included in this study, with 3994 patients of mild CHD, 7195 patients of moderate CHD and 2067 patients of complex CHD. The prevalence of stunting, underweight and FTT was 24%, 29.3% and 36.9%, respectively. Preoperative anaemia, left ventricle systolic dysfunction, younger age, more complex CHD types, lower birth weight and genetic syndrome were found to be the risk factors for FTT in CHD patients. Interrupted aortic arch was revealed to be the most severe group associated with FTT.
UNASSIGNED: FTT is ubiquitous in patients with CHD and exacerbated in high-risk subgroups. Our findings hinted the necessity of early identification and intervention for FTT in patients with CHD during daily practice of pediatrics, as it has the potential to improve outcomes and enhance their quality of life. Furthermore, we advocate for the initiation of prospective research with longitudinal data to comprehensively investigate the association between FTT and CHD across the lifespan.
UNASSIGNED: This study was supported by National High Level Hospital Research Funding (2022-GSP-GG-19), Capital Health Research and Development of Special Fund (2022-1-4032) and National Key R&D Program of China (2022YFC3600202 and 2022YFC3600203).

2岁以内婴幼儿生长减缓是临床常见问题，尤其是在低收入贫困地区。临床对生长减缓的婴幼儿要尽早识别、评估和诊断，积极消除病因，通过监测、营养管理、喂养行为指导让生长减缓婴幼儿实现适宜的追赶生长，回到原来的生长轨迹上。.

OBJECTIVE: To explore the genetic basis of a child with Very early onset inflammatory bowel disease (VEOIBD).
METHODS: A female child who had presented at the Children\'s Hospital of Fudan University on May 23, 2018 due to occurrence of diarrhea and fever 6 days after birth was selected as the study subject. Clinical data of the child was collected. Family-based whole-exome sequencing (WES) was carried out. Candidate variant was verified by Sanger sequencing and PCR of the patient and her parents.
RESULTS: The child had developed the symptoms 6 days after birth, with main manifestations including diarrhea, fever, failure to thrive, rectovestibular fistula and hypothyroidism. An enterostomy was performed at the age of 3.5 months due to severe intestinal adhesion and obstruction. Based on her clinical manifestations, colonoscopic finding, and results of biopsies, she was diagnosed with VEOIBD in conjunct with congenital hypothyroidism. Replacement treatment of levothyroxine was given since one month of age. Family-based WES revealed that the child has harbored compound heterozygous variants of the DUOX2 gene, namely c.2654G>T (p.R885L) and c.505C>T (p.R169W), in addition with a heterozygous c.301C>T (p.R101W) variant of the IL10RA gene. Re-analysis of the WES data revealed that the patient also had a 333 bp deletion spanning exon 1 of the IL10RA gene (Chr11: 117857034_117857366).
CONCLUSIONS: For patients with VEOIBD, genetic testing is recommended. Presence of additional DUOX2 gene variants might have exacerbated the clinical symptoms in this patient. Above finding has facilitated genetic counseling and prenatal diagnosis for this family, and raised clinicians\' awareness of this rare disease.

Shwachman-Diamond syndrome (SDS) is an autosomal recessive disease which results in inherited bone marrow failure (IBMF) and is characterized by exocrine pancreatic dysfunction and diverse clinical phenotypes. In the present study, we reviewed the internationally published reports on SDS patients, in order to summarize the clinical features, epidemiology, and treatment of SDS.
We searched the WangFang and China National Knowledge Infrastructure databases with the keywords \"Shwachman-Diamond syndrome,\" \"SDS,\" \"SBDS gene\" and \"inherited bone marrow failure\" for relevant articles published from January 2002 to October 2022. In addition, studies published from January 2002 to October 2022 were searched from the Web of Science, PubMed, and MEDLINE databases, using \"Shwachman-diamond syndrome\" as the keyword. Finally, one child with SDS treated in Tongji Hospital was also included.
The clinical features of 156 patients with SDS were summarized. The three major clinical features of SDS were found to be peripheral blood cytopenia (96.8%), exocrine pancreatic dysfunction (83.3%), and failure to thrive (83.3%). The detection rate of SDS mutations was 94.6% (125/132). Mutations in SBDS, DNAJC21, SRP54, ELF6, and ELF1 have been reported. The male-to-female ratio was approximately 1.3/1. The median age of onset was 0.16 years, but the diagnostic age lagged by a median age of 1.3 years.
Pancreatic exocrine insufficiency and growth failure were common initial symptoms. SDS onset occurred early in childhood, and individual differences were obvious. Comprehensive collection and analysis of case-related data can help clinicians understand the clinical characteristics of SDS, which may improve early diagnosis and promote effective clinical intervention.

OBJECTIVE: The 12q14 microdeletion syndrome is a rare genetic condition characterized by intrauterine growth restriction, proportionate short stature, failure to thrive, and intellectual disability. Few reports have discussed the therapeutic aspect of patients with 12q14 microdeletion syndrome. Herein, we report the first case of 12q14 microdeletion patient treated with rhGH without growth hormone deficiency.
METHODS: The patient presented with feeding difficulties during infancy, failure to thrive, intellectual disability and subtle dysmorphic facial features. The patient first visited the clinic at 5 years and 3 months, his height was 91.4 cm (-4.9 SD) and weight 10.0 kg (-2.86 SD). The growth hormone level was within the normal range. Bone radiological testing revealed no significant abnormalities. Genetic analysis identified a 6.97 Mb deletion at the chromosome 12q14.1-q14.3 region in the proband. Recombinant human growth hormone therapy was initiated, which lasted for 12 months, and the new height was 101.0 cm (-4.0 SD) and weight 12.0 kg (-3.6 SD).
CONCLUSIONS: This report first showed that patient with 12q14 microdeletion, although without growth hormone deficiency, can benefit from human growth hormone therapy.

Adenosine deaminase (ADA) is a key enzyme in the purine salvage pathway. Genetic defects of the ADA gene can cause a subtype of severe combined immunodeficiency. To date, few Chinese cases have been reported.
We retrospectively reviewed the medical records of patients diagnosed with ADA deficiency in Beijing Children\'s Hospital and summarized the previously published ADA deficiency cases from China in the literature.
Nine patients were identified with two novel mutations (W272X and Q202 =). Early-onset infection, thymic abnormalities and failure to thrive were the most common manifestations of Chinese ADA-deficient patients. The ADA genotype has a major effect on the clinical phenotype. Notably, a novel synonymous mutation (c.606G>A, p.Q202=) was identified in a delayed-onset patient, which affected pre-mRNA splicing leading to a frameshift and premature truncation of the protein. Furthermore, the patient showed γδT cells expansion with an increased effect or phenotype, which may be associated with the delayed onset of disease. In addition, we reported cerebral aneurysm and intracranial artery stenosis for the first time in ADA deficiency. Five patients died with a median age of four months, while two patients received stem cell transplantation and are alive.
This study described the first case series of Chinese ADA-deficient patients. Early-onset infection, thymic abnormalities and failure to thrive were the most common manifestations in our patients. We identified a synonymous mutation that affected pre-mRNA splicing in the ADA gene, which had never been reported in ADA deficiency. Furthermore, we reported cerebral aneurysm in a delayed-onset patient for the first time. Further study is warranted to investigate the underlying mechanisms.

Faltering growth (FG) is a problem regularly seen by clinicians in infants and young children (<2 years of age). It can occur due to non-disease-related and disease-related causes and is associated with a wide range of adverse outcomes, including shorter-term effects such as impaired immune responses and increased length of hospital stay, and longer-term consequences, including an impact on schooling and cognitive achievements, short stature, and socioeconomic outcomes. It is essential to detect FG, address underlying causes and support catch-up growth where this is indicated. However, anecdotal reports suggest misplaced fear of promoting accelerated (too rapid) growth may deter some clinicians from adequately addressing FG. An invited international group of experts in pediatric nutrition and growth reviewed the available evidence and guidelines on FG resulting from disease-related and non-disease-related effects on nutritional status in healthy term and small for gestational age infants and children up to the age of 2 years in low-, middle-, and high-income countries. Using a modified Delphi process, we developed practical consensus recommendations to provide clarity and practical recommendations for general clinicians on how FG should be defined in different young child populations at risk, how FG should be assessed and managed, and the role of catch-up growth after a period of FG. We also suggested areas where further research is needed to answer remaining questions on this important issue.

Laboratory and clinical studies have revealed the importance of gut microbiota in children with severe pediatric pathological conditions such as severe acute malnutrition (SAM); however, under relatively milder conditions such as, failure to thrive (FTT), the role of the gut microbiota remains poorly characterized. Here, we analyzed stool samples from 54 subjects with a clinical diagnosis of failure to thrive (FTT), 49 preterm subjects with corrected normal growth (NFTT-pre), and 49 healthy subjects (NFTT) between 3-12 months of age using 16S rRNA gene sequencing. We observed that the clinical condition of FTT, age, head circumference, intrauterine growth restriction (IUGR), and feeding methods significantly affected gut microbiota. The microbiota age of subjects was significantly correlated with their anthropomorphic features, and the FTT subjects exhibited underdeveloped gut microbiota characterized by a significantly decreased microbiota-for-age Z-score (MAZ). The FTT and NFTT-pre groups exhibited an obvious disrupted developmental trajectory of gut microbiota across age, and the development of their alpha diversities and the observed OTU and Shannon indices were inadequate, particularly in subjects with FTT. Moreover, sequential colonization and enrichment of bacteria such as Bacteroides, Bifidobacterium, Streptococcus and most age-discriminatory bacterial taxa and their microbial functions were disorganized in FTT compared to that in NFTT. Our results revealed an underdevelopment of the gut microbiota in infants with failure to thrive that possesses potential clinical and practical importance.

OBJECTIVE: To explore the genotype-phenotype correlation of a patient with cardio-facio-cutaneous syndrome (CFCS) due to variant of the MAP2K1 gene.
METHODS: DNA was extracted from peripheral blood samples of the infant and his parents and subjected to whole exome sequencing. Candidate variant was verified by Sanger sequencing.
RESULTS: The patient had typical CFCS facies and developmental delay, and was found to harbor a de novo heterozygous c.389A>G (p.Tyr130Cys) missense variant in exon 3 of the MAP2K1 gene. Based on the American college of Medical Genetics and Genomics guidelines, this variant was classified as likely pathogenic.
CONCLUSIONS: This patient has differed from previously reported cases by having no cardiac anomaly or seizures but typical facial features and skin abnormalities accompanied by growth retardation, intellectual impairment, and urinary malformation. It has therefore enriched the phenotypic spectrum of CFCS due to variants of the MAP2K1 gene.