Hypothesis: Central digit hypoplasia.

Area of Science:

• Medical Genetics
• Birth Defects Surveillance
• Developmental Biology

Background:

• Limb deficiencies are common congenital anomalies.
• Accurate phenotyping is crucial for understanding limb malformations and providing genetic counseling.
• Existing classifications may not fully capture specific limb deficiency patterns.

Purpose of the Study:

• To characterize specific limb deficiency phenotypes using data from a long-term malformations surveillance program.
• To define and describe a distinct limb deficiency pattern termed 'central digit hypoplasia'.
• To differentiate central digit hypoplasia from other limb defects like terminal transverse limb defects, symbrachydactyly, and amniotic band syndrome.

Main Methods:

• Analysis of data from a 41-year malformations surveillance program (1972-2012) at Brigham and Women's Hospital, encompassing 289,365 births.
• Inclusion of newborns, stillborn fetuses, and fetuses from elective terminations with limb deficiencies.
• Identification of affected individuals through medical record review and autopsy findings.

Main Results:

• 194 infants and fetuses with limb deficiencies were identified.
• Three distinct limb deficiency phenotypes were characterized.
• Seventeen cases of 'central digit hypoplasia' were identified, defined by hypoplasia of the thumb and fifth finger with soft tissue remnants in place of central digits.

Conclusions:

• Central digit hypoplasia represents a distinct limb deficiency phenotype.
• Accurate identification and differentiation from conditions like symbrachydactyly and amniotic band syndrome are essential.
• Precise phenotyping improves genetic counseling for affected infants and their families.