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RASopathies: Clinical Diagnosis in the First Year of Life
M C Digilio1, F Lepri, A Baban
1Medical Genetics and Pediatric Cardiology, Bambino Gesù Pediatric Hospital, IRCCS.
Insights
Early diagnosis of RASopathies in infants is challenging. Key early signs like heart defects, feeding issues, and skin anomalies can help differentiate these rare genetic disorders.
Area of Science:
- Genetics
- Pediatrics
- Clinical Medicine
Background:
- Diagnosing RASopathies in early infancy is difficult due to delayed manifestation of key clinical features.
- Early identification is crucial for timely management and improved outcomes in RASopathies.
Purpose of the Study:
- To identify and characterize early clinical features of RASopathies within the first year of life.
- To improve the diagnostic accuracy of RASopathies in neonates and infants.
- To enhance understanding of the natural history of RASopathies.
Main Methods:
- Retrospective review of clinical records from 57 molecularly confirmed RASopathy subjects.
- Analysis focused on clinical data from the first year of life.
- Correlation of specific clinical features with molecularly confirmed RASopathy subtypes.
Main Results:
- Facial dysmorphia was universally present in all infants.
- Congenital heart defects were prominent in Noonan and LEOPARD syndromes.
- Feeding difficulties and motor delays were common in cardiofaciocutaneous and Costello syndromes.
- Specific features like thin hair (SHOC2, BRAF), café-au-lait spots (LS, PTPN11), and keratosis pilaris (SOS1, SHOC2, BRAF) aided in differentiating subtypes.
Conclusions:
- Certain clinical signs in the first year of life can suggest a RASopathy diagnosis.
- Specific early manifestations, including congenital heart defects, feeding issues, developmental delays, and skin/hair anomalies, aid in distinguishing between different RASopathies.
- Early clinical suspicion facilitates molecular confirmation and appropriate patient management.
Abstract:
Diagnosis within Noonan syndrome and related disorders (RASopathies) still presents a challenge during the first months of life, since most clinical features used to differentiate these conditions become manifest later in childhood. Here, we retrospectively reviewed the clinical records referred to the first year of life of 57 subjects with molecularly confirmed diagnosis of RASopathy, to define the early clinical features characterizing these disorders and improve our knowledge on natural history. Mildly or markedly expressed facial features were invariably present. Congenital heart defects were the clinical issue leading to medical attention in patients with Noonan syndrome and LEOPARD syndrome. Feeding difficulties and developmental motor delay represented the most recurrent features occurring in subjects with cardiofaciocutaneous syndrome and Costello syndrome. Thin hair was prevalent among SHOC2 and BRAF mutation-positive infants. Café-au-lait spots were found in patients with LS and PTPN11 mutations, while keratosis pilaris was more common in individuals with SOS1, SHOC2 and BRAF mutations. In conclusion, some characteristics can be used as hints for suspecting a RASopathy during the first months of life, and individual RASopathies may be suspected by analysis of specific clinical signs. In the first year of life, these include congenital heart defects, severity of feeding difficulties and delay of developmental milestones, hair and skin anomalies, which may help to distinguish different entities, for their subsequent molecular confirmation and appropriate clinical management.
