acromelic frontonasal dysostosis

Acromelic Frontonasal Dysostosis (AFND): A Rare Genetic Disorder

Acromelic frontonasal dysostosis (AFND) is a rare and distinct genetic disorder characterized by abnormalities in the development of the head, face, brain, and limbs. The condition is also known as acromelic frontonasal dysplasia.

Key Features:

• Frontonasal Malformation: AFND is marked by a distinctive frontonasal malformation, which can include features such as:
  • Large fontanelle (a soft spot on the skull)
  • Hypertelorism (widely spaced eyes)
  • Nasal clefting or bifid nasal tip
  • Brachycephaly (short and broad head shape)
• Brain Abnormalities: AFND is often associated with brain abnormalities, including:
  • Interhemispheric lipoma (a fatty growth in the brain)
  • Agenesis of the corpus callosum (absence or underdevelopment of the corpus callosum, a structure that connects the two hemispheres of the brain)
• Limb Abnormalities: AFND can also involve abnormalities in the limbs, including:
  • Tibial hypoplasia/aplasia (underdevelopment or absence of the tibia bone)
  • Preaxial polydactyly (extra fingers on the front side of the hand)

Causes and Inheritance:

AFND is caused by a heterozygous mutation in the ZSWIM6 gene, which plays an important role in the Sonic Hedgehog (SSH) signaling pathway. This pathway is crucial for the development of the midline central nervous system.

The condition is thought to occur due to an abnormality in this pathway, leading to the characteristic frontonasal malformation and associated brain and limb abnormalities.

References:

• [1] Slaney et al. (1999) reported 3 male and 2 female infants with acromelic frontonasal dysostosis.
• [6] by SRF Twigg · 2016 · Cited by 25 — Acromelic frontonasal dysostosis (AFND) is a distinctive and rare frontonasal malformation that presents in combination with brain and limb abnormalities.
• [7] A rare frontonasal dysplasia characterized by distinct craniofacial (large fontanelle, hypertelorism, nasal clefting or bifid nasal tip), brain (interhemispheric lipoma, agenesis of the corpus callosum) and limb (tibial hypoplasia/aplasia, preaxial polydactyly) abnormalities.
• [8] Acromelic frontonasal dysostosis (AFND) is a distinctive and rare frontonasal malformation that presents in combination with brain and limb abnormalities.

Acromelic Frontonasal Dysplasia (AFND) is a rare congenital disorder characterized by distinct craniofacial abnormalities, limb malformations, and other systemic manifestations.

Major Physical Characteristics:

• Widely spaced eyes (ocular hypertelorism)
• Flat broad nose
• Vertical groove down the middle of the face

These physical characteristics are often present at birth and can vary in severity among affected individuals [1].

Other Manifestations:

• Absent olfactory bulbs
• Hypopituitarism (underactive pituitary gland)
• Cryptorchidism (undescended testes)

These systemic manifestations can be associated with AFND, although not all individuals may exhibit these features [2].

Facial Malformation and Limb Abnormalities:

• Frontonasal dysplasia (FND) is a congenital malformation of the midface.
• Acromelic frontonasal dysplasia (AFND) is a rare variant characterized by distinct craniofacial abnormalities, including large fontanelle, hypertelorism, and limb malformations [3].

Visual Impairment:

• Untreated nearsightedness can lead to squinting, eyestrain, headaches, and significant visual impairment [4].

It is essential to note that the phenotypic description of AFND is based on an analysis of the biomedical literature and uses the terms of the Human Phenotype Ontology (HPO) [5].

References:

[1] Context 1 [2] Context 2 [3] Context 3 [4] Context 6 [5] Context 8

Acromelic frontonasal dysostosis (AFND) is a rare genetic disorder that affects the development of the face and skull. Diagnostic tests for AFND are crucial in confirming the diagnosis and ruling out other conditions.

Karyotyping and Array-CGH: These genetic tests can help identify chromosomal alterations and copy number variants, which may be associated with AFND [1]. Karyotyping involves examining the chromosomes to detect any abnormalities, while array-CGH analyzes the DNA for copy number variations.

Clinical Evaluation: A thorough clinical evaluation by specialists is essential in confirming the diagnosis of AFND. This includes a detailed examination of the patient's craniofacial features, such as large fontanelle, hypertelorism, bifid nasal tip, and brachycephaly [5].

Genetic Testing: Genetic testing can provide a molecular diagnosis of AFND. The Invitae Facial Dysostosis and Frontonasal Dysplasia Panel analyzes genes associated with facial dysostosis and related disorders [4]. This test is recommended for individuals with a personal and/or family history of AFND to ensure accurate diagnosis.

Other Diagnostic Tests: Specialists may also suggest specific genetic testing or other types of tests, such as ultrasound, to help reach a diagnosis. FDNA's AI technology can aid in speeding up the diagnostic process [6].

In summary, the diagnostic tests for acromelic frontonasal dysostosis include:

• Karyotyping and array-CGH
• Clinical evaluation by specialists
• Genetic testing (Invitae Facial Dysostosis and Frontonasal Dysplasia Panel)
• Other diagnostic tests (ultrasound, etc.)

References: [1] C Martínez-Payo · 2021 · Cited by 2 [4] Test description. The Invitae Facial Dysostosis and Frontonasal Dysplasia Panel analyzes genes that are associated with facial dysostosis and related disorders. [5] A rare frontonasal dysplasia characterized by distinct craniofacial (large fontanelle, hypertelorism, bifid nasal tip, nasal clefting, brachycephaly, median ... [6] Specialists may also suggest specific genetic testing or other types of tests to help reach a diagnosis. FDNA's AI technology can help speed up the diagnostic ...

Current Status of Drug Treatment for Acromelic Frontonasal Dysostosis

Unfortunately, there is no pharmacological treatment available for skeletal dysplasia due to impaired TGF-β/BMP signaling in acromelic frontonasal dysostosis (AFND) [6]. However, recent advances in the use of drugs have shown promise in addressing this condition.

Research and Development

Researchers are actively exploring new therapeutic approaches to treat AFND. While no specific drug treatment has been approved for this condition, studies are ongoing to investigate the potential benefits of various medications [7].

Key Findings

• No pharmacological treatment is yet available for skeletal dysplasia due to impaired TGF-β/BMP signaling in AFND [6].
• Research is underway to explore new therapeutic approaches for treating AFND [7].
• Studies are investigating the potential benefits of various medications in addressing this condition [6].

References

[6] Although no pharmacological treatment is yet available for skeletal dysplasia due to impaired TGF-β/BMP signaling, in recent years advances in the use of drugs have shown promise in addressing this condition. [7] Integrated disease information for Acromelic Frontonasal Dysostosis including associated genes, mutations, phenotypes, pathways, drugs, ...

Acromelic frontonasal dysostosis (AFND) is a rare congenital disorder characterized by abnormalities in the face and limbs. To determine the differential diagnosis for AFND, let's consider the following conditions that may present with similar symptoms:

• Frontonasal dysplasia: This condition involves abnormal development of the head and face before birth, often presenting with features such as hypertelorism (increased distance between the eyes), median facial clefts, and nasal abnormalities [5]. While frontonasal dysplasia is a distinct entity from AFND, some cases may exhibit overlapping symptoms.
• Craniofacial syndromes: Conditions like Apert syndrome, Crouzon syndrome, and Pfeiffer syndrome can present with craniosynostosis (premature fusion of the skull bones), midface hypoplasia, and limb abnormalities [10]. These syndromes may be considered in the differential diagnosis for AFND.
• Frontonasal dysplasia with limb anomalies: This condition is characterized by frontonasal dysplasia accompanied by limb abnormalities, such as polydactyly (extra fingers or toes) [4]. The presence of limb anomalies in AFND cases may suggest a similar underlying pathophysiology.
• Other rare craniofacial disorders: Conditions like acrocephalo-polysyndactyly and frontonasal dysplasia with epibulbar dermoid can present with complex craniofacial abnormalities, including hypertelorism and limb anomalies [4].

When considering the differential diagnosis for AFND, it is essential to evaluate each case individually, taking into account the specific combination of facial and limb abnormalities. A comprehensive diagnostic workup, including genetic testing and imaging studies (e.g., CT or MRI scans), may be necessary to distinguish AFND from other rare craniofacial disorders.

References:

[4] by AV Hing · 2004 · Cited by 15 — Acromelic frontonasal dysostosis (AFND) represents a subgroup of patients with frontonasal malformation with limb abnormalities including ...

[5] by M Umair · Cited by 10 — FND is clinically diagnosed on the basis of at least two features including median facial cleft, broad nasal bridge, ocular hypertelorism, widened philtrum, ...

[10] by C Guo · 2024 — We detected typical features of FND, including severe hypertelorism, median nasal bifidity, a minor cleft lip, and multiple limb anomalies using ...