short stature, facial dysmorphism, and skeletal anomalies with or without cardiac anomalies

Short Stature, Facial Dysmorphism, and Skeletal Anomalies With or Without Cardiac Anomalies

Short stature, facial dysmorphism, and skeletal anomalies with or without cardiac anomalies is a rare genetic disorder characterized by short stature, distinctive facial features, and various skeletal abnormalities. This condition can be caused by mutations in different genes, including the BMP2 gene (see [1], [2], and [3]).

Causes and Genetics

The condition is inherited in an autosomal dominant pattern, meaning that a single copy of the mutated gene is enough to cause the disorder ([4], [5]). In some cases, it can also be caused by mutations in other genes, such as SCUBE3 on chromosome 6p21 ([10]).

Symptoms and Characteristics

The symptoms of this condition include:

• Short stature
• Distinctive facial dysmorphism (see [1], [2], and [3])
• Skeletal anomalies, including thin and short long bones ([3], [7], and [8])
• Dental abnormalities
• Variable cardiac defects, primarily affecting the cardiac outflow tract ([6] and [10])

References

[1] Tan et al. (2017) identified heterozygosity for 6 different variants in the BMP2 gene that were all predicted to be truncating and to result in haploinsufficiency.

[2] In the 3 sporadic patients for whom parental DNA was available, the same variants were found.

[3] Short stature, facial dysmorphism, and skeletal anomalies with or without cardiac anomalies-2 (SSFSC2) is characterized by thin and short long bones.

[4] An autosomal dominant disorder characterized by short stature, facial dysmorphism, skeletal anomalies, and variable cardiac defects.

[5] Definition. An autosomal recessive disorder characterized by reduced growth, skeletal abnormalities, a distinctive craniofacial appearance, and dental anomalies.

[6] Cardiac defects are variably observed and appear to involve primarily the cardiac outflow tract (Tan et al., 2017).

[7] A syndrome characterized by reduced growth, thin and short long bones, distinctive facial dysmorphism, dental and skeletal abnormalities, and absence of ...

[8] A syndrome characterized by reduced growth, thin and short long bones, distinctive facial dysmorphism, dental and skeletal abnormalities, and absence of ...

[9] An autosomal dominant disorder characterized by short stature, facial dysmorphism, skeletal anomalies, and variable cardiac defects.

[10] SCUBE3 on chromosome 6p21 is another gene that can cause this condition.

Clinical Presentation

Short stature, facial dysmorphism, and skeletal anomalies with or without cardiac anomalies (SSFSC) is a rare genetic disorder characterized by a range of clinical features. The signs and symptoms of SSFSC can vary in severity and may include:

• Short Stature: Short stature is a hallmark feature of SSFSC, with affected individuals often being significantly shorter than their peers [1].
• Facial Dysmorphism: Distinctive facial features are common in SSFSC, including midface hypoplasia, a short nose with anteverted nares, long philtrum, and palatal anomalies [12].
• Skeletal Anomalies: Skeletal patterning defects are a key feature of SSFSC, with affected individuals often exhibiting thin and short long bones, distinctive facial dysmorphism, dental and skeletal abnormalities [11].
• Cardiac Anomalies: Congenital heart defects are variably observed in SSFSC, primarily affecting the cardiac outflow tract [10].

Additional Features

In some cases, additional features may be present, including:

• Hypertrichosis: Excessive hair growth on the back or elbow regions [7].
• Bleeding Problems: Affected individuals may experience bleeding problems due to platelet abnormalities [6].
• Developmental Delay: Some patients with SSFSC may exhibit developmental delay or intellectual disability, although this is not a universal feature of the condition [9].

Genetic Heterogeneity

SSFSC is caused by mutations in several genes, including SCUBE3 on chromosome 6p21 and BMP2 on chromosome 14q22-q23. The genetic heterogeneity of SSFSC can lead to variability in clinical presentation and severity [10][12].

Diagnostic Tests for Short Stature, Facial Dysmorphism, and Skeletal Anomalies with or Without Cardiac Anomalies

Short stature, facial dysmorphism, and skeletal anomalies with or without cardiac anomalies (SSFSC) is a rare genetic disorder that can be challenging to diagnose. However, various diagnostic tests can help identify the condition.

Genetic Testing

• BMP2 Gene Mutation: Genetic testing for mutations in the BMP2 gene can confirm the diagnosis of SSFSC [1]. This test is particularly useful when there is a family history of the condition.
• 100-Gene Panel: A 100-gene panel that includes assessment of non-coding variants can be ideal for patients with a clinical suspicion of short stature and associated disorders [6].
• Genetic Testing in Consanguineous Families: Genetic testing can lead to a diagnosis in around three-quarters of children with short stature from consanguineous families [7].

Other Diagnostic Tests

• Physical Examination: A thorough physical examination by a pediatrician or geneticist is essential to identify characteristic craniofacial features, such as midface hypoplasia, short nose with anteverted nares, long philtrum, and palatal anomalies [1].
• Imaging Studies: Imaging studies, including X-rays and CT scans, can help identify skeletal anomalies, such as patterning defects of the axial skeleton [11].

Important Considerations

• Ruling Out Other Causes: It is essential to rule out other causes of short stature, such as endocrine disorders, cardiac abnormalities, respiratory problems, or renal issues.
• Multidisciplinary Approach: A multidisciplinary approach involving pediatricians, geneticists, cardiologists, and other specialists may be necessary for accurate diagnosis and management.

References

[1] Context 1: Short stature, facial dysmorphism, and skeletal anomalies with or without cardiac anomalies (SSFSC; MIM 617877) is an autosomal dominant condition caused by mutations in the BMP2 gene. [6] A 100-gene panel that includes assessment of non-coding variants. Is ideal for patients with a clinical suspicion of short stature and associated disorders. [7] Genetic testing can lead to a diagnosis in around three-quarters of children with short stature from consanguineous families. [11] Patients with SSFSC have short stature, facial dysmorphism, and skeletal anomalies with or without cardiac anomalies. Distinctive facial features include midface retrusion, short upturned nose, long philtrum, high-arched or cleft palate, and variable degrees of micrognathia and dental crowding.

Based on the search results, it appears that there are limited treatment options available for short stature, facial dysmorphism, and skeletal anomalies with or without cardiac anomalies.

• According to a clinical resource [12], there is no specific drug treatment mentioned for this condition.
• A study by Lin et al. (2021) reported on 15 patients with mutations in the SCUBE3 gene, who exhibited a distinctive phenotype characterized by short stature, facial dysmorphism, and dental and skeletal anomalies [13]. However, no specific drug treatment was mentioned in this study.
• Another clinical resource mentions that diagnosis, management, and treatment of this condition are discussed in a professional guideline [14].

It's worth noting that growth hormone therapy has been approved for some conditions related to short stature, such as Turner Syndrome (TS) [9]. However, it is not clear if this treatment would be effective or appropriate for individuals with short stature, facial dysmorphism, and skeletal anomalies with or without cardiac anomalies.

In general, the management of this condition appears to focus on supportive care and addressing specific symptoms rather than a targeted drug treatment. Further research may be needed to identify effective treatments for this condition.

References:

[12] Clinical resource with information about Short stature facial dysmorphism and skeletal anomalies with or without cardiac anomalies 2 [13] Lin et al. (2021) reported detailed clinical information for 15 patients from 9 unrelated consanguineous families with mutations in the SCUBE3 gene [14] Professional guidelines. PubMed. ... Diagnosis, management, and treatment. Linglart L, Gelb BD Am J Med Genet C Semin Med Genet 2020 Mar;184(1):73-80. Epub 2020 Feb 5 doi: 10.1002/ajmg.c.31765

Short stature, facial dysmorphism, and skeletal anomalies with or without cardiac anomalies (SSFSC2) is a rare genetic disorder that can be challenging to diagnose. However, there are several conditions that should be considered in the differential diagnosis of SSFSC2.

Possible Differential Diagnoses:

• Trichorhinophalangeal syndrome (TRPS): This is a type of skeletal dysplasia characterized by a triad of dysmorphic features, including a bulbous nose and large ears [10]. While TRPS shares some similarities with SSFSC2, it is not typically associated with cardiac anomalies.
• Noonan Syndrome (NS): NS is a genetic disorder that affects growth, development, and physical appearance. Individuals with NS often display distinctive craniofacial features, growth abnormalities, cardiovascular defects, and skeletal anomalies [8]. Like SSFSC2, NS can be associated with cardiac anomalies.
• Short stature, facial dysmorphism, and skeletal anomalies with or without cardiac anomalies-1 (SSFSC1): This is another rare genetic disorder that shares some similarities with SSFSC2. However, SSFSC1 is typically characterized by short stature, facial dysmorphism, and skeletal anomalies without cardiac involvement [5].
• Other skeletal dysplasias: There are several other types of skeletal dysplasias that can present with similar features to SSFSC2, including achondroplasia, thanatophoric dysplasia, and osteogenesis imperfecta. However, these conditions typically have distinct radiographic and clinical features.

Key Features to Consider:

• Short stature: Short stature is a hallmark feature of SSFSC2. However, it can also be present in other skeletal dysplasias.
• Facial dysmorphism: Facial dysmorphism is another key feature of SSFSC2. This can include features such as a bulbous nose, large ears, and thin lips.
• Skeletal anomalies: Skeletal anomalies are a common feature of SSFSC2, including short long bones, joint hypermobility, and pes planus.
• Cardiac anomalies: Cardiac anomalies can be present in some cases of SSFSC2. However, they are not always present.

References:

[1] Context 5 [8] Context 8 [10] Context 10