the AJMG SEQUENCE
In this issue
Parents Of Chinese Rett Syndrome Patients Encounter Difficulties
The frustrations of Chinese families affected by Rett syndrome (RS) could in part be addressed by more information and support for them, better clinician education and training, and more genetic testing to confirm the clinical diagnosis, according to Lim et al (p. 1).
RS, a rare neurological disorder that affects girls, is usually caused by a MECP2 mutation. About 1,000 girls with RS are born every year in China, but far fewer are diagnosed.
Telephone interviews with members of 14 of the 74 Chinese families known to the International Rett Syndrome Phenotype Database explored routes to RS diagnosis and associated barriers. Families consulted multiple clinical centers and eventually received a diagnosis at a centrally located hospital. Families encountered lack of RS knowledge and diagnostic expertise at local levels and a heavily over-burdened hospital system. After diagnosis, families and clinicians had little information to guide management of the disorder.
About 1,000 girls with RS are born every year in China, but far fewer are diagnosed.
In light of China's one-child policy, Chinese families want to plan for their family's needs and to better understand their daughters.
New Auriculo-condylar syndrome cases described
Kokitsu-Nakata et al (p. 59) detail new individual and familial cases of auriculo-condylar syndrome (ACS).
Characterized by malformed “question mark” ears, prominent cheeks, microstomia, and abnormal temporomandibular joint and condyle of the mandible, ACS's genetic cause is unknown.
One patient is a simplex case and the other is from a previously unreported family with affected individuals in three generations that document clinical variability.
Both patients had typical ACS facial appearance and clinical findings. The familial case had mild facial phenotype, as did the rest of the affected relatives. Among them, the pattern of ear anomalies (so-called “question mark” ear) was somewhat variable.
Figure 3A. Clinical aspects of Patient 2
The clinical overlap between ACS and other pharyngeal arch disorders, mainly oculoauriculoverte-bral spectrum (0AVS), sometimes represents a diagnostic challenge. Description of new familial cases with ACS and with 0AVS might clarify if the clinical overlap between both conditions represents a common genetic mechanism, the researchers write.
Molecular Basis For Poland Anomaly Evades Researchers
Baban et al (p. 140) write that they couldn't determine a molecular basis for Poland anomaly (PA) with recurrence risk or clinical tools for spotting it.
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.
Researchers evaluated 240 patients with PA and 190 of their parents and classified them into 3 groups: those with familial PA (F-PA) that involved pectoral muscle defects with familial recurrence, familial Poland-like anomaly families (F-PLA) in which at least one relative showed normal pectoral muscles but ULA and/or TA common in PA, and those with sporadic PA.
F-PA patients tended to have a stronger male (87.5%) and left side (62.5%) prevalence, but fewer ULA (37.5%) compared to the other 2 groups. Maternal transmission was more common in F-PA.
Researchers performed karyotyping and array comparative genomic hybridization in 13 families. They identified the following maternally inherited copy number variants in only 3 patients: 1p31.1 deletion, Xp11.22 duplication, and 16q23.1 duplication.
Figure 1A. Sagittal extended field-of-view 17-5 MHz US image obtained in the right (left) parasternal area reveals partial agenesis of the pectoralis major muscle. Superficial to the rib cage, only the clavicular head (arrows) of the pectoralis major muscle is seen. II, second rib; III, third rib; IV, fourth rib.