Familial Poland anomaly revisited

Abstract

Poland anomaly (PA) is a pectoral muscle hypoplasia/aplasia variably associated with ipsilateral thoracic (TA) and/or upper limb anomalies (ULA). PA is usually sporadic and sometimes familial, making recurrence risk an issue in genetic counseling. Multidisciplinary evaluation of 240 PA patients was carried out, including physical examination of patients and their parents in 190 PA (subjects of the study). Familial conditions were classified into three groups. Group1: true familial PA (F-PA): pectoral muscle defects with familial recurrence: 8(4.2%). Group2: familial Poland-like anomaly families (F-PLA): PA index case and ≥1 relative(s) showing normal pectoral muscles but ULA and/or TA common in PA: 16(8.4%). Group3: sporadic PA (S-PA): 166(87.4%). F-PA indicated a stronger male (87.5%) and left side (62.5%) prevalence, but fewer ULA (37.5%) compared to the other two groups. Maternal transmission (6/8) was more common in F-PA. Statistical significance was not reached due to the small number of F-PA and F-PLA. Karyotyping and array-comparative genomic hybridization were performed in 13 families. Three maternally inherited copy number variants were identified in three patients: 1p31.1 deletion, Xp11.22 duplication, and 16q23.1 duplication. Interestingly, the proband's mother carrying the 16q23.1 duplication displayed moderate breast and areola asymmetry, but normal pectoral muscles on ultrasound. Though there is no recent review discussing recurrence of PA, we reviewed 31 published PA families. On the basis of our study and previous reports, familial PA is not uncommon. Nonetheless, no information can be derived either regarding a molecular basis or clinical tools with which to identify cases with recurrence risk.

Assessment of copy number variations in 120 patients with Poland syndrome

“…PS patients present with pectoralis muscle agenesis/hypoplasia, more frequently on the right side. PS can be associated with a variable degree of ipsilateral thoracic and/or upper limb anomalies [1, 2]. Incidence of PS has been reported between 1/20,000 and 1/30,000 births with a higher prevalence in males [3, 4].…”

“…Alternatively, PS may be due to the involvement of genes regulating embryonic development of pectoral girdle [7]. Familial recurrence was observed in about 10% of cases with different inheritance patterns including autosomal dominant with incomplete penetrance, autosomal recessive, and X-linked [1]. The presence of different genes whose mutations may account for clinical differences among subgroups of patients and for the different inheritance patterns observed could be hypothesized.…”

De novo deletion of chromosome 11q12.3 in monozygotic twins affected by Poland Syndrome

“…The classic hand deformity in PS includes syndactyly and variable degrees of brachydactyly with hypoplasia or aplasia of the middle phalanges (reviewed in [1,2]). The incidence of PS was reported to be 1/30,000-32,000 births with higher prevalence in males and a male to female ratio estimated between 2:1 and 3:1 [3-5]. The pathogenic mechanisms underlying PS are still unknown.…”

“…One hypothesis states that PS defects could result from a vascular insult during early embryological stages, which implies that environmental factors could contribute to PS phenotype [6,7]. However, though most cases of PS are sporadic, familial recurrence with higher prevalence in males has been observed, which suggests a genetic basis of this congenital anomaly [3]. Different inheritance patterns, including autosomal recessive, autosomal dominant, and dominant with incomplete penetrance, have been reported and, therefore, genetic heterogeneity might be expected (reviewed in [3]).…”

“…However, though most cases of PS are sporadic, familial recurrence with higher prevalence in males has been observed, which suggests a genetic basis of this congenital anomaly [3]. Different inheritance patterns, including autosomal recessive, autosomal dominant, and dominant with incomplete penetrance, have been reported and, therefore, genetic heterogeneity might be expected (reviewed in [3]). Impaired development of structures involved in PS may be hypothesized, suggesting a pathogenic mechanism involving genes regulating cell proliferation and/or differentiation during development.…”