This article reports on the clinical and genetic characteristics of monozygotic twins with Marshall-Smith syndrome (MRSHSS) due to a mutation in the NFIX gene, along with a review of related literature. Both patients presented with global developmental delays, a prominent forehead, shallow eye sockets, and pectus excavatum. Genetic testing revealed a heterozygous splicing site mutation c.697+1G>A in both children, with parents showing wild-type at this locus. According to the guidelines of the American College of Medical Genetics and Genomics, this mutation is considered likely pathogenic and has not been previously reported in the literature. A review of the literature identified 32 MRSHSS patients with splicing/frameshift mutations. Accelerated bone maturation and moderate to severe global developmental delay/intellectual disability are the primary clinical manifestations of patients with MRSHSS. Genetic testing results are crucial for the diagnosis of this condition.
该文报道了一对NFIX基因变异导致Marshall-Smith综合征（Marshall-Smith syndrome, MRSHSS）的同卵双胞胎临床及遗传学特点并对相关文献进行复习。2例患儿均表现为全面发育落后、高额头、浅眼眶、漏斗胸。基因检测提示2例患儿均存在NFIX杂合剪接位点变异c.697+1G>A，父母该位点为野生型，根据美国医学遗传学与基因组学学会指南判定为可能致病性变异，该位点突变既往未见文献报道。复习文献共发现32例MRSHSS患者，突变类型为剪切/移码突变。骨骼成熟加速、中至重度全面发育迟缓/智力障碍是MRSHSS患者最主要的临床表现。基因检测结果是该病重要的诊断依据。.

BACKGROUND: Trisomy 20p is a rare genetic condition caused by a duplication of the short arm of chromosome 20.
METHODS: We employed clinical observation and molecular genetic testing (SNP microarray), to study identical twin males with an unknown dysmorphic syndrome. We conducted a literature review of trisomy 20p and collated the clinical and molecular genetic findings on 20 affected subjects reported since 2000.
RESULTS: Identical twin males, whose prenatal course was complicated by a twin-to-twin transfusion, manifested profound language and neurocognitive delays as well as distinctive facial dysmorphisms when evaluated at 2 years of age. SNP microarray identified identical duplications of 20p13 with no other chromosomal aberrations. A literature survey of 20p trisomy syndrome identified 20 other examples of this condition reported since 2000, which we collated with 33 summarized by Sidwell et al. (2000). Within the combined total of 55 affected individuals, we found a distinctive clinical phenotype that provides insight on the effects of abnormal dosage of genes in 20p13. These loci include FAM110A (OMIM 611393), ANGPT4 (OMIM 603705), RSPO4 (OMIM 610573), PSMF1 (OMIM 617858), SNPH (OMIM 604942), SDCBP2 (OMIM 617358), FKBP1A (OMIM 186945), TMEM74B, C20orf202, and RAD21L1 (OMIM 619533). Gene profiling highlighted that syntaphilin (SNPH) is highly expressed in mammalian brain, where it is considered critical for mitochondrial transport in neuronal axons, and to directly influence axonal morphogenesis and function.
CONCLUSIONS: We propose that abnormal activity of syntaphilin engendered by the trisomy is primarily responsible for the language, neurocognitive, and gross motor delays reported in individuals with 20p trisomy. Additional studies, for example, characterization of cerebral organoids generated from affected patients may help to better understand this condition, and potentially suggest rational remedies to improve the lives of affected individuals and their families.

This systematic review explores cardiac adaptation in monochorionic (MC) twins with twin-twin transfusion syndrome (TTTS) or selective fetal growth restriction (sFGR) and assesses the risk of congenital heart defects (CHDs).
Adhering to PRISMA guidelines, 63 studies were reviewed (49 on cardiac adaptation, 13 on CHD, one on both). A narrative synthesis of cardiac adaptation patterns was performed. Additionally, a meta-analysis compared the livebirth prevalence of CHD in TTTS and sFGR against uncomplicated MC twins.
In TTTS recipients, cardiac function may be impaired for diastolic, systolic, as well as global functions, while in donors, cardiac function is generally preserved. In sFGR, large twins may show hypertrophic cardiomyopathy, and small twins may show impaired systolic function. Co-occurrence of TTTS and sFGR magnifies cardiac impact but is often underreported. Meta-analysis for CHD prevalence revealed a relative risk ratio of 3.5 (95% CI: 2.5-4.9) for TTTS and 2.2 (95%CI: 1.3-3.5) for sFGR compared with uncomplicated MC twins.
This study highlights the well-documented cardiac adaptation in TTTS, contrasting with limited understanding in sFGR. Elevated CHD risks were observed in both conditions. Enhanced cardiovascular surveillance is warranted in complicated MC twin pregnancies. Future research should explore cardiac adaptation in sFGR and its long-term consequences.

The authors present the cases of monozygotic male twins with right-sided Legg-Calvé-Perthes disease (LCPD) with different formation of the lumbosacral junction. This is likely the fi rst description of a lumbosacral junction formation disorder associated with identical twins who were both treated for LCPD as children. The disease began at 6 and 9 years of age and during treatment as well as in adulthood signifi cantly different bone formation of the lumbosacral transitional vertebra, was observed in both brothers. Twin A has a unilateral right-sided fusion of the enlarged L5 transverse process with the ipsilateral sacral ala, twin B has a complete sacralization of the fi fth lumbar vertebra. The LCPD treatment outcomes in the twins were consistent with the results from large studies, i.e., age at the time of LCPD onset is the main factor infl uencing the prognosis, however the morphological difference in the transitional vertebrae in these monozygotic twins was signifi cantly. Key words: lumbosacral transitional vertebra, lumbosacral junction formation, sacralization of lumbar vertebra, megatransverse of vertebra L5.

Feto-fetal hemorrhage (FFH) through placental vascular anastomoses is believed to be responsible for the death or damage of a \"second twin\" after the demise of a \"first twin (co-twin)\" in monochorionic twin pregnancies. However, the timing of FFH has been difficult to determine. The resulting anemia in the surviving twin can be suspected by the finding of an elevated middle cerebral artery peak-systolic velocity (MCA-PSV), but this elevation may lag for at least 4 h after the demise of the first twin. Knowledge of the timing of FFH may have important clinical implications, as it may dictate if and when attempts to prevent death or damage to the second twin by delivery or intrauterine fetal transfusion would be warranted. We present a case that supports the notion that FFH occurs before the actual demise of the first twin. A review of the literature was also conducted.

Glanzmann thrombasthenia (GT) is a rare bleeding disorder with a high prevalence in communities where consanguineous marriages are mainstream. Endometriosis is a chronic inflammatory disease, and its risk increases in women with menstrual periods of longer than six days. The phenotypic expression of endometriosis is determined by the frequency and rate of the menstrual flow, as well as genetic and environmental factors.
14-year-old monozygotic twin sisters with GT who developed ovarian endometriosis were referred to Hazrat Rasoul Hospital due to severe dysmenorrhea. In ultrasonic examination, endometrioma cysts were reported in both patients. They both went under endometrioma cystectomy, and the bleeding was managed using antifibrinolytic drugs, followed by recombinant activated coagulation factor VII. Both were discharged after 3 days. In the ultrasound examination performed one year after the surgery, ovaries were normal in the first twin, while the second twin had a 28 × 30 hemorrhagic cyst in the left ovary.
Menstrual bleeding and genetic factors are two theories that could be related to GT and endometriosis association, and GT could be considered a risk factor for endometriosis.

Reared-apart twin studies are a powerful means for identifying the relative contributions of heredity and environment to variation in human physical and behavioural traits. One such characteristic is handedness, for which it has long been noted that approximately 20% of twin pairs are comprised of one right-handed cotwin and one left-handed cotwin. Reared-together twin studies suggest a slightly greater concordance in monozygotic (MZT) than dizygotic (DZT) twins, implying that genetics influences hand preference. We report here two studies of handedness in reared-apart twins. Study 1 synthesizes the available data and estimates that at least N = 560 same-sex reared-apart twin pairs (for which zygosity is known with reasonable confidence) have been identified. Of these, handedness data are available for both members of n = 415 pairs. We observed similar levels of concordance/discordance for reared-apart monozygotic (MZA) and dizygotic (DZA) twins. However, although direction of handedness (right or left) has frequently been examined, strength of handedness (strong or weak) has not. Study 2 examined strength of hand preference and relative hand skill, as well as right- and left-hand speed, information available for participants in the Minnesota Study of Twins Reared Apart (MISTRA). We provide evidence of heritability for right-hand and left-hand speed. We also found hand preference strength was more alike than chance in DZA, but not MZA, twins. Findings are discussed in relation to genetic and environmental influences on human handedness.

Selective fetal growth restriction (sFGR) complicates 10%-26% of monochorionic twins. Treatment options include cord coagulation, expectant management, and fetoscopic laser photocoagulation. This review compared laser to expectant management for situations when cord coagulation is not an option. The MEDLINE, EMBASE, and Cochrane databases were queried for studies that compared laser to expectant management for sFGR. GRADE was used to assess quality prior to meta-analysis. A random-effects model was used to generate relative risks. Six studies were included, encompassing 299 pregnancies. One study was randomized and the remainder were retrospective cohorts. Laser is associated with more fetal deaths of the FGR twin compared to expectant management (risk ratio [RR] 2.5, 95% confidence interval [CI] 1.43-4.37, p = 0.001, I2 = 48%). Neonatal deaths and gestational age at delivery did not differ. Laser was associated with decreased abnormal neuroimaging in the AGA twin (RR 0.25, 95% CI 0.07-0.97, p = 0.05). Neurodevelopmental outcomes did not differ, although these data are limited. Laser causes more fetal deaths of the FGR twin without altering gestational age at delivery or rates of neonatal death. The literature is heterogeneous and the level of bias is high. Randomized trials that address laser for type II sFGR are needed and should include long-term neurological outcomes.

UNASSIGNED: To compare the outcomes of dichorionic triamniotic (DCTA) triplets with that of monochorionic diamniotic (MCDA) twin gestations undergoing fetoscopic laser surgery (FLS) for treatment of twin-to-twin transfusion syndrome (TTTS).
UNASSIGNED: Retrospective cohort study of prospectively collected data of consecutive DCTA triplet and MCDA twin pregnancies with TTTS that underwent FLS at two fetal treatment centers between 2012 and 2020. Preoperative, operative and, postoperative variables were collected. Perinatal outcomes were investigated. Primary outcome was survival to birth and to neonatal period. Secondary outcomes were gestational age (GA) at birth and procedure-to-delivery interval. Literature review was conducted in which PubMed, Web of Science, and Scopus were searched from inception to September, 2020.
UNASSIGNED: Twenty four sets of DCTA triplets were compared to MCDA twins during the study period. There were no significant differences in survival (no survivor, single, or double survivors) to birth and to the neonatal period of the MC twin pairs of the DCTA triplets vs MCDA twins. Median GA at delivery was approximately three weeks earlier in DCTA triplets compared to MCDA twins (28.4 weeks vs 31.4 weeks, p = .035, respectively). Rates of preterm birth (PTB) less than 32 and less than 28 weeks were significantly higher in DCTA triplets compared to twins (<32 weeks: 70.8% vs 51.1%, p = .037, respectively, and <28 weeks: 37.5% vs 20.8%, p = .033, respectively).
UNASSIGNED: Perinatal survival including fetal and neonatal are comparable between DCTA triplets and MCDA twins. However, this might have resulted from the small sample size of the DCTA triplets. GA at delivery is earlier in triplets, which could be due to the nature of triplet gestation rather than to the laser procedure itself.

Through a systematic review and meta-analyses, we aimed to analyze the impact of chorionicity on neurodevelopment outcomes.
We conducted a comprehensive search strategy through Medline, Embase, Web of Science, and reference lists of the retrieved studies until August 2022. Studies that examined the association between chorionicity and children\'s neurodevelopment outcomes were included.
Twelve studies were included. Monochorionic (MC) twins increased the odds of neurodevelopment impairment, cerebral palsy compared to dichorionic (DC) twins. The differences in neurodevelopmental impairment and cerebral palsy between the two groups disappeared after excluding infants with twin-twin transfusion (TTTS). After fetoscopic laser surgery (FLS) for MC twins, there were no differences too.
Compared to DC twins, MC twins were associated with an increased risk of neurodevelopment impairment. MC twins complicated by TTTS were at high risk of neurologic disability, and FLS was an acceptable treatment modality for them.