terminal osseous dysplasia

Terminal osseous dysplasia, also known as Terminal osseous dysplasia with pigmentary defects (TODPD), is a rare genetic disorder that primarily affects the skeletal system and skin.

Key Features:

• Skeletal abnormalities: The condition is characterized by malformation of the hands and feet, shortening and/or bowing of the bones in the arms and legs, and other limb anomalies.
• Pigmentary skin lesions: Affected individuals often have pigmentary skin lesions on the face and scalp.
• Digital fibromatosis: Recurring digital fibroma (a type of tumor) is a common feature of this condition.

Genetic Cause:

Terminal osseous dysplasia is caused by mutations in the FLNA gene, which provides instructions for producing the protein filamin A. This protein plays a crucial role in building the cytoskeleton and allowing cells to change shape, move, and interact with neighboring cells [1].

Inheritance Pattern:

The condition is inherited in an X-linked dominant pattern, meaning that a single copy of the mutated gene is sufficient to cause the disorder. Males are more severely affected than females, and the condition is often lethal in males [5][6][7][9].

References:

[1] - The FLNA gene provides instructions for producing the protein filamin A, which helps build the network of protein filaments (cytoskeleton) that gives structure to cells and allows them to change shape, move, and interact with neighboring cells. [from search result 1]

[5] - Terminal osseous dysplasia is an X-linked dominant male-lethal disease characterized by skeletal dysplasia of the limbs, pigmentary defects of the skin, and recurrent digital fibroma during infancy (Sun et al., 2010). [from search result 11]

[6] - Terminal osseous dysplasia with pigmentary defects: Clinical description of a new family ... Terminal osseous dysplasia with pigmentary defects is an extremely rare condition characterized by the triad of pigmentary anomalies of the skin, skeletal abnormalities of the limbs and recurring digital fibromatosis of childhood, with considerable [from search result 12]

[7] - Terminal osseous dysplasia with pigmentary defects (TODPD; OMIM 300244) is a disorder characterized by pigmentary anomalies of the skin, skeletal abnormalities, mainly involving the limbs, digital fibromas, multiple oral frenula, iris colobomas, cardiac, and urogenital malformations. [from search result 13]

[9] - Terminal osseous dysplasia with pigmentation abnormalities; X-linked otopalatodigital syndrome type 1 (OPD1) These names reflect the various features and aspects of the condition. Terminal osseous dysplasia is associated with changes in genes located on the X chromosome. Specifically, mutations in the FLNA gene cause this condition [from search result 14]

Terminal osseous dysplasia, also known as terminal osseous dysplasia-pigmentary defects syndrome, is a rare genetic disorder characterized by skeletal abnormalities and pigmentary skin lesions.

Skeletal Abnormalities:

• Permanently bent fingers and toes (camptodactyly) [1]
• Malformation of the hands and feet
• Deformity and tumor-like swelling of fingers and toes [9]

Pigmentary Skin Lesions:

• Dark facial patches [6]
• Fibromas on fingers or toes [6]
• Multiple pigmented lesions localized to the face and scalp [7, 9]

Other Signs and Symptoms:

• Accessory oral frenulum
• Cleft palate
• Depressed nasal tip
• Epicanthus
• Telecanthus
• Thick vermilion border
• Upslanted palpebral fissure [3]
• Extra oral frenulae
• Widely spaced eyes
• Hair loss [6]

Systemic Abnormalities:

• Affected females may display multiple systemic abnormalities such as limb deformities and pigmented lesions of the face and scalp [8]
• Short stature or slow growth
• Disproportionately large head, especially the forehead
• Disproportionately short upper arms [10]

Terminal osseous dysplasia, also known as Terminal osseous dysplasia-pigmentary defects syndrome, can be diagnosed through various diagnostic tests.

• Clinical Molecular Genetics test: This test is used to diagnose Terminal osseous dysplasia-pigmentary defects syndrome and involves deletion/duplication analysis and Next-Generation Sequencing (NGS) [3].
• Genetic testing: Genetic testing for Terminal osseous dysplasia can be performed using Deletion/Duplication Analysis, NGS, or other molecular genetic techniques. This test is used to identify the FLNB gene mutation associated with the condition [4, 5].
• Imaging studies: Imaging studies such as X-rays and CT scans may be used to confirm skeletal abnormalities and assess the extent of bone involvement.
• Dermatological examination: A dermatological examination can help identify pigmentary skin lesions on the face and scalp, which are characteristic of Terminal osseous dysplasia-pigmentary defects syndrome [4].
• Orthopedic evaluation: An orthopedic evaluation is necessary to assess skeletal abnormalities and malformation of the hands and feet.

It's worth noting that a diagnosis of Terminal osseous dysplasia-pigmentary defects syndrome can be established in a male proband with characteristic clinical and radiographic features and a family history consistent with X-linked inheritance [11].

Diagnostic teams for Terminal osseous dysplasia-pigmentary defects syndrome may include:

• Dermatology
• Genetics
• Orthopedics
• Rare Disease Experts

It's essential to consult with a healthcare professional, such as a geneticist or an orthopedic specialist, to determine the best course of action and diagnostic tests for Terminal osseous dysplasia-pigmentary defects syndrome.

Terminal osseous dysplasia, also known as terminal osseous dysplasia with pigmentary defects (TODPD), is a rare genetic disorder characterized by skeletal abnormalities and certain skin changes. When considering the differential diagnosis for this condition, several other disorders come to mind:

• Skeletal dysplasias: These are a group of disorders that affect the development of bones and cartilage. Other types of skeletal dysplasias, such as achondroplasia or osteogenesis imperfecta, may present with similar skeletal abnormalities.
• Pigmentary defects: Certain conditions, like piebaldism or Waardenburg syndrome, can cause pigmentary changes in the skin, which may be similar to those seen in terminal osseous dysplasia.
• X-linked dominant disorders: As terminal osseous dysplasia is an X-linked dominant disorder, other conditions with a similar inheritance pattern, such as Aicardi syndrome or Rett syndrome, should also be considered.

Some of the key features that distinguish terminal osseous dysplasia from these other conditions include:

• Skeletal abnormalities: Terminal osseous dysplasia is characterized by skeletal dysplasia of the limbs, which may involve shortening or deformity of the bones.
• Pigmentary defects: The condition is also associated with pigmentary changes in the skin, such as hypopigmentation or hyperpigmentation.
• Male lethality: Terminal osseous dysplasia is a male-lethal disease, meaning that affected males do not survive to birth.

In terms of specific diagnostic criteria, terminal osseous dysplasia can be distinguished from other conditions by the presence of:

• Terminal skeletal dysplasia: This refers to the characteristic shortening or deformity of the bones in the limbs.
• Pigmentary defects: The condition is associated with pigmentary changes in the skin, which may involve hypopigmentation or hyperpigmentation.
• X-linked dominant inheritance: Terminal osseous dysplasia is inherited in an X-linked dominant pattern, meaning that affected females display multiple symptoms.

Overall, a comprehensive differential diagnosis for terminal osseous dysplasia should consider other skeletal dysplasias, pigmentary defects, and X-linked dominant disorders. However, the unique combination of skeletal abnormalities, pigmentary changes, and male lethality in terminal osseous dysplasia can help to distinguish it from these other conditions.

References:

• [3] Terminal osseous dysplasia with pigmentary defects (TODPD; MIM #300244) is an extremely rare, X-linked dominant, in utero male-lethal disease, characterized by skeletal dysplasia of the limbs, pigmentary defects of the skin, and other systemic features.
• [5] Terminal osseous dysplasia (TOD) is an X-linked dominant male-lethal disease characterized by skeletal dysplasia of the limbs, pigmentary defects of the skin, and other systemic features.
• [7] Terminal osseous dysplasia and pigmentary defects is a rare X-linked dominant disorder with prenatal male lethality. Affected females display multiple symptoms, including terminal skeletal dysplasia, pigmentary defects of the skin, and other systemic features.
• [8] Terminal osseous dysplasia (MIM 300244) is a rare condition, characterized by terminal skeletal dysplasia, pigmentary defects of the skin, and other systemic features.