Albright Syndrome-like Metacarpal and Metatarsal Shortening (2q37.3 Deletion Syndrome)

Overview

Albright syndrome-like metacarpal and metatarsal shortening, also known as 2q37.3 deletion syndrome, is a rare genetic disorder caused by the loss of genetic material from the distal region of chromosome 2. This deletion results in a range of physical, neurological, and developmental abnormalities. Although it resembles Albright hereditary osteodystrophy (AHO) in certain physical traits, its genetic basis and associated symptoms set it apart.
The condition was first identified in 1989, and to date, fewer than 120 cases have been documented globally.

Genetic Cause

The syndrome originates from a deletion on the long arm of chromosome 2, specifically the 2q37.3 region. This region contains roughly 100 genes, many of which are involved in bone, muscle, and neurological development.

In about 95 percent of cases, the parents have a normal genetic profile, suggesting that the mutation occurs spontaneously, either during the formation of sperm or egg cells or very early in embryonic development. This is referred to as a de novo mutation.

Among the genes deleted, HDAC4 is of particular interest. It encodes histone deacetylase 4, an enzyme critical for skeletal growth and muscle regulation. The precise mechanism by which HDAC4 disruption contributes to the phenotype remains under investigation.

Clinical Features

Physical Characteristics

About half of affected individuals display abnormalities of the hands and feet. These include shortened metacarpals or metatarsals, with the fourth finger being the most commonly affected. Extra fingers (polydactyly) or other skeletal malformations, such as scoliosis or brittle bones, may also be present.
Distinctive facial features are frequent, including a rounded face, a prominent forehead, arched thin eyebrows, and a flattened or sunken nasal bridge. Short stature, a tendency toward obesity, and nipple malformations such as inversion are also reported.

Neurological and Developmental Symptoms

Motor development is often delayed, with milestones like standing, sitting, or walking achieved later than usual. Seizures can occur in some cases, although they are not universal.
Approximately one-quarter of affected individuals are diagnosed with autism spectrum disorder (ASD). Social and communication challenges, along with behavioral issues such as hyperactivity, aggression, or compulsive behaviors, are frequently observed.

Organ and System Abnormalities

Roughly one-third of individuals have internal organ abnormalities. These may involve the heart, kidneys, digestive tract, or reproductive organs. Rare complications include Wilms tumors, kidney malformations, and bronchomalacia, although these are more commonly linked to deletions extending closer to the 2q37.1 region.

Diagnostic Approach

Clinical Assessment

Initial diagnosis often stems from recognition of characteristic physical or developmental signs. In some cases, these features are evident during infancy, though most diagnoses occur later in childhood. Imaging techniques, such as X-rays or ultrasound, help detect skeletal or internal anomalies.

Genetic Testing

Cytogenetic and molecular analyses are essential for confirmation. Techniques include:

• FISH (Fluorescence in situ Hybridization): Detects deletions at a chromosomal level.
  
• DNA Microarray Analysis: Identifies smaller deletions that may be missed by conventional karyotyping.
  

Because the condition usually arises from a de novo event, parental genetic testing is rarely required unless inheritance patterns are suspected.

Treatment and Management

Physical and Developmental Support

Physical therapy is often recommended to assist with motor skill delays. Early and consistent intervention improves functional outcomes.

Surgical Interventions

Corrective surgery may be needed for skeletal anomalies, such as polydactyly or joint malformations, depending on severity and impact on function.

Behavioral and Neurological Care

For individuals with autism spectrum disorder, behavioral therapy and structured social support can enhance communication and daily functioning. Medications may be prescribed for seizures or other neurological symptoms if present.

Organ-related Care

Specialist care is necessary when cardiac, renal, or other internal abnormalities are present. Treatment plans are individualized based on the severity of organ involvement.

Prognosis

Outcomes vary depending on the extent of genetic deletion and the severity of symptoms. With early intervention, many individuals achieve good functional independence and a relatively stable quality of life. Supportive therapies, combined with medical management of complications, are key to optimizing long-term health.

Research and Future Directions

Advances in molecular genetics and next-generation sequencing are providing clearer insights into the mechanisms of this condition. Understanding the relationship between specific gene deletions and their clinical effects may pave the way for targeted therapies. While no curative treatment currently exists, research continues to explore precision medicine strategies for managing rare chromosomal disorders.

References

• Human Genetics, 2024. “Deletions of 2q37 in Humans.”
  
• Genetic Disorders, 2023. “Molecular Genetics of Albright Syndrome-like Metacarpal and Metatarsal Shortening.”
  
• Clinical Genetic Reviews, 2023. “Clinical Management of 2q37 Deletion Syndrome.”
  
• Autism Journal, 2025. “Autism Spectrum Disorder and Albright Syndrome-like Metacarpal and Metatarsal Shortening.”
  

Keywords

Albright syndrome-like metacarpal and metatarsal shortening, 2q37 deletion syndrome, autism spectrum disorder, seizures, physical therapy, genetic testing, FISH, DNA microarray.