Background: The occurrence of multiple endocrine neoplasia type 2B (MEN2B) in Asians is very rare. In particular, patients with intractable constipation as the main clinical manifestation are even rarer. Atypical clinical manifestations are likely to lead to a diagnostic delay. In this report, we described a case of a delayed diagnosis of MEN2B, and the first clinical manifestation was intractable constipation. Case presentation: A female teenager had suffered from intractable constipation since infancy. Because the colonoscopy and biopsy results from local hospitals did not confirm the presence of congenital megacolon, the girl had been followed up at a local clinic for a long time. The diagnosis was not confirmed until thyroid masses were found in the Pediatric Department of Shanghai Ruijin Hospital when she was 12 years old. According to our detailed evaluation, she suffered from Hirschsprung disease (HD), growth retardation, medullary thyroid carcinoma (MTC) and mucosal neuroma due to a mutation in the RET gene. Thus, the diagnosis of MEN2B was confirmed. Afterward, the girl underwent several surgeries and was still being followed up before the article was published. Conclusion: MEN2B has atypical clinical symptoms in the early stage. Refractory constipation may be the only clinical manifestation that lasts for several years. Therefore, we recommend that early screening and gene sequencing should be performed for patients with severe constipation due to HD to determine the cause of the disease and to improve the survival outcome.

To investigate the unique features of inflammatory bowel disease (IBD) in children, we wanted to identify whether there might be a strong correlation between the disease phenotype and its prognosis at various ages in paediatric patients. We collected data from patients diagnosed with IBD (ulcerative colitis (UC) or Crohn’s disease (CD)) from 2002 to 2016. The diagnosis was made according to the Porto criteria and Paris Classification. Patient characteristics, clinical manifestations and treatments were collected. Risk factors for surgery, mortality and relapse were analysed by Cox proportional hazard models. Of the 143 patients, 113 had CD, and 30 had UC; there were 89 males and 54 females with a median age of 9 years (y). Thirteen patients in the 0–2 y group were identified as having mutations in IL-10 receptor A, and this mutation was significantly more common in this age group than in 3–9 and 10–16 y patients. The risk factor for surgery was the B3 phenotype; risk factors for death were age 0–2 y and B3 phenotype; 0–2 y, B3 phenotype and steroid dependency were risk factors for early relapse. Clinical manifestations of the onset of IBD in infants and toddlers were extensive and aggressive and were closely associated with early relapse and death. It is of particular interest that some of these patients developed IBD due to monogenic disorders; thus, introduction of genetic testing is essential for these patients.

Background: Hypospadias is a common congenital malformation of male external genitalia, which mainly manifests as an abnormal urethral opening on the ventral side of the penis. The etiology and clinical phenotype of hypospadias is highly heterogeneous, and its clinical diagnosis is challenging. Currently, over 70% of patients have an unknown etiology. Here, we performed a targeted analysis of gene mutations in 130 patients with hypospadias of unknown etiology to find the precise genetic cause.Methods: We developed a targeted next‐generation sequencing (NGS) panel, encompassing the exon coding regions of 105 genes involved in external genitalia and urogenital tract development and performed sequencing analysis on 130 children with hypospadias of unknown etiology.Results: In total, 25 patients with hypospadias (19.2%) were found to have 20 mutations among the nine genes involved in external genitalia and urogenital tract development, including 16 reported and four novel mutation sites. Twenty‐two patients (16.9%) had diagnostic variants. Multiple genetic mutations were identified in three of the 25 patients. Hypospadias combined with micropenis was the most common phenotype (68%) in 25 patients.Conclusions: Higher frequency mutations were identified in SRD5A2 (52%) and AR (24%) in our patient cohort. Middle or posterior hypospadias with micropenis may be significant indicators of genetic variations. Polygenic inheritance may be a rare genetic cause of hypospadias.

Autosomal recessive 333 base pair interleukin 10 receptor alpha subunit deletion in very early-onset inflammatory bowel disease

Background: The etiology of short stature is heterogeneous. The disturbance of endochondral ossification and cartilage matrix synthesis caused by genetic mutations often causes short height combined with skeletal deformities in children. Some patients with minor skeletal abnormalities, such as short fingers and mild limb shortening, may be overlooked by clinicians and misdiagnosed as idiopathic short stature (ISS) or growth hormone deficiency (GHD). Case Description: We conducted a detailed investigation of laboratory and imaging examinations on a family with short stature and non-classical brachydactyly type A1 (BDA1) and summarized the clinical features. They received whole exome sequencing (WES) to reveal the possible genetic variation. A heterozygous mutation in the Indian hedgehog gene (IHH) (c.387_388insC, p.Thr130Hisfs*18) was found in the two siblings and their mother. The siblings both started recombinant human growth hormone (rhGH) therapy (rhGH: 33 µg/kg/day) and followed up for 4 years. After treatment, the siblings’ height improved significantly, and they acquired a significant increase in the height standard deviation score (SDS) (the boy: +2.54, the girl: +1.86) during the 4-year therapy. No noticeable adverse effect was observed during rhGH treatment. Conclusions: We found a novel heterozygous pathogenic mutation in the IHH gene in a family and detailed the phenotype with short stature and non-classical BDA1. The therapy of rhGH showed promising effects. To avoid misdiagnosis, clinicians should not overlook minor skeletal anomalies in patients with short stature, especially those with a family history.