Renal-hepatic-pancreatic dysplasia type 2: Perinatal lethal condition or a multisystemic disorder with variable expressivity.

BACKGROUND: Renal-hepatic-pancreatic dysplasia type 2 (RHPD2) is a rare condition that has been described in the literature disproportionately in perinatal losses. The main features of liver and kidney involvement are well described, with cardiac malformations and cardiomyopathy adding additional variation to the phenotype. Many patients reported are within larger cohorts of congenital anomalies of kidney and urinary tract (CAKUT) or liver failure, and with minimal phenotypic and clinical course data. METHODS: An independent series of phenotypes and prognosis was aggregated from the literature. In this literature review, we describe an additional patient with RHPD2, provide a clinical update on the oldest known living patient, and report the cumulative phenotypes from the existing published patients. RESULTS: With now examining the 17 known patients in the literature, 13 died within the perinatal period-pregnancy to one year of life. Of the four cases living past the first year of life, one case died at 5 years secondary to renal failure, the other at 30 months secondary to liver and kidney failure. Two are currently alive and well at one year and 13 years. Two cases have had transplantation with one resulting in long-term survival. CONCLUSIONS: These patients serve to expand the existing phenotype of RHPD2 as a perinatal lethal condition into a pediatric disorder with variable expressivity. Additionally, we introduce the consideration of transplantation and outcomes within this cohort and future patients.

Genetics in the NICU: Nurses' Perceived Knowledge and Desired Education.

Background Many infants admitted to the neonatal intensive care unit (NICU) have genetic conditions. Previous research has shown that gaps exist in the genetics knowledge of nurses and that they lack comfort applying genetics information to clinical practice. Studies assessing the knowledge or comfort of NICU nurses with genetics have not previously been completed. Method A total of 122 NICU nurses completed a survey assessing perceived knowledge of genetics, comfort with clinical scenarios involving genetics, and desired genetics education. Results Perceived knowledge and overall comfort were correlated with highest degree received, how prepared a nurse felt by the genetics education received in their training, and having a close relationship with someone with a genetic condition. Almost all respondents (96%, n = 117) desired additional genetics education. Conclusion Gaps exist in the genetics knowledge of neonatal nurses in our cohort, and their overall comfort working with clinical scenarios involving genetics was low. There is significant interest in additional genetics education. [J Contin Educ Nurs. 2023;54(1):16-24.].

Laparoscopic ovarian tissue harvesting for cryopreservation from a child with galactosemia.

OBJECTIVE: To describe an approach to fertility preservation by a multidisciplinary team of reproductive endocrinology and infertility, pediatric gynecology and surgery, and genetics experts via ovarian tissue harvesting and cryopreservation for a toddler with galactosemia. Galactosemia is associated with progressive primary ovarian insufficiency (POI) and early intervention with ovarian tissue cryopreservation may help preserve fertility. DESIGN: Video description of a tissue harvesting and cryopreservation technique. SETTING: Academic institution. PATIENT(S): 16-month-old female with classic galactosemia. INTERVENTION(S): At 6 months of age, despite good metabolic control, the infant's antimüllerian hormone (AMH) level was <0.015 ng/ml; luteinizing hormone level was 3.1 mIU/ml; and follicle stimulating hormone level was 30.2 mIU/ml. She was referred by her geneticist to the reproductive endocrinology and infertility specialist for fertility preservation. The AMH levels and pelvic magnetic resonance imaging findings of the patient were monitored over the next 9 months. Although the magnetic resonance imaging exam showed the presence of a dominant follicle in the right ovary and multiple small antral follicles in both ovaries at the age of 8 months, her laboratory assessment at the age of 14 months suggested impending POI (estradiol level <11.80 pg/mL; LH, 3.3 mIU/ml; follicle stimulating hormone, 35.97 mIU/ml; AMH, 0.03 ng/mL). At 16 months of age, given the low AMH levels, right ovary was laparoscopically harvested, so that a sufficient reserve of primordial follicles may be cryopreserved for fertility preservation. We dissected the mesosalpinx initially to separate the ovary from the tube in a manner that minimized the effects of cauterization on the ovary and preserved the fallopian tube. MAIN OUTCOME MEASURE(S): Successful harvesting and cryopreservation of the ovarian tissue containing primordial follicles. RESULT(S): The right ovary, which measured 20 × 3 × 3mm, was bisected under a stereomicroscope along the hilum, trimmed to the cortical thickness of 1 mm and sliced into eight 4 × 4-mm pieces. These were then frozen with an established slow freezing protocol. The child was discharged the same day and had an uneventful postoperative course. A subsequent histological examination showed presence of primordial follicles, albeit at a reduced density for her age. CONCLUSION(S): Ovarian tissue cryopreservation is feasible in very young female children with rare genetic disorders associated with POI. We illustrated the unique aspects of performing these procedures in very young children.

Clinical and biochemical outcomes in cobalamin C deficiency with use of high-dose hydroxocobalamin in the early neonatal period.

This case report describes a patient with early-onset cobalamin C deficiency who was started on treatment with high-dose parenteral hydroxocobalamin after diagnosis at 13 days of life. Prior to diagnosis, initial presenting symptoms included poor feeding, lethargy, apneic episodes, hypothermia, and hypotonia; these symptoms resolved after initiation of medication. Methylmalonic acid and homocysteine levels were trended and significantly improved with treatment. She was maintained on 2 mg/kg/day dosing of hydroxocobalamin. No adverse effects to treatment were observed. At the time of this report, the patient was 19 months of age; she had not manifested common findings of early-onset cobalamin C deficiency, including microcephaly, poor feeding, growth abnormalities, hypotonia, seizures, maculopathy, or neurodevelopmental delay. This report suggests that early initiation of high-dose hydroxocobalamin is safe and effective.

Frequency of Sex Chromosome Involvement in a Large Cohort of Subjects with Two Copy Number Variants.

Copy number variants (CNVs) are a common finding in the clinical setting and contribute to both genetic variation and disease. Studies have described the accumulation of multiple CNVs as a disease-modifying mechanism. While it has been described how additional CNVs may play a role in phenotype, in which ways and to what extent sex chromosomes are involved in dual CNV scenario has not been fully defined. To describe the distribution of CNVs, a secondary data analysis using the DECIPHER database on 2,273 de-identified individuals with two CNVs was performed. CNVs were designated larger and secondary based on size and characteristics. We found that the X chromosome was observed to be the most common chromosome involved in secondary CNVs. Further analysis showed CNVs on the sex chromosome have significant differences compared to autosomes when comparing median size (p = 0.013), pathogenicity groups (p < 0.001), and variant classification (p = 0.001). Lastly, we identified chromosome combinations for larger and secondary CNVs and observed the plurality of secondary CNVs fell in the same chromosome as the larger. The observations of this study provide additional information on sex chromosome CNV involvement in a variety of indications.

The youngest pair of siblings with Mucopolysaccharidosis type IVA to receive enzyme replacement therapy to date: A case report.

Mucopolysaccharidosis type IVA (OMIM 253000) is an autosomal recessive disorder caused by defective activity of the N-acetylgalactosamine 6-sulfatase (GALNS) enzyme. In 2014, enzyme replacement therapy (ERT) using recombinant human GALNS became available for affected patients. There is a limited number of studies to date that have explored the effect of ERT in infancy and there is also a lack of data assessing the effect of ERT in systems other than the skeletal. Here, we report on the effect of ERT in the youngest pair of siblings treated to date: Patient A, currently 4 years old, who started treatment at the age of 5 months; and Patient B, currently 3 years old, who started treatment at 58 days of life. Moreover, we investigate the effect of early ERT on the cardiovascular system. Our results show that, even when ERT is started before 2 months of age, it cannot fully prevent disease progression. As for the effect of ERT on the cardiovascular system, our preliminary results suggest that early treatment might play a role in preserving a normal left ventricular mass index in affected patients at least up to 1 year, but further observation over time will be required. Overall, this report shows that early diagnosis remains crucial and that prompt initiation of ERT has limited effect in slowing progression of the skeletal phenotype, thus confirming the need for new therapeutic approaches that target the skeletal system in affected patients.

Two new reported cases of 16q22.3q23.3 duplication syndrome highlight intrafamilial variability and potential sex expression differences within a rare duplication syndrome.

Two new cases of 16q22.3q23.3 Duplication syndrome demonstrate that phenotype can vary from severely affected to mild psychiatric concerns, even within the same family and identical duplications.