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8Q22.1 DELETION ALONE DOES NOT CAUSE NABLUS MASK-LIKE FACIAL SYNDROME

Allanson et al. (p. 2091, DOI: 10.1002/ajmg.a.35446) find that deletion of the 8q21.3q22.1 region is necessary, but not enough, to develop Nablus mask-like facial syndrome (NMLFS).

The condition has many distinctive phenotypic features, particularly tight glistening skin with reduced facial expression, blepharophimosis, telecanthus, bulky nasal tip, abnormal external ear architecture, upswept frontal hairline, and sparse eyebrows. Over the last few years, microarray analysis of several individuals with NMLFS has found a microdeletion of 8q21.3q22.1. The minimal overlapping region is 93.98–96.22 Mb (hg19).

The authors present clinical and microarray data from five individuals and two mother–child pairs with heterozygous deletions that have significant overlapping with the NMLFS-associated region. Although one mother–child pair was said to have mild tightening of facial skin, the authors found that neither of these individuals exhibited reduced facial expression or the classical facial phenotype of NMLFS.

The authors suggest possible genetic mechanisms underlying the complex pattern of inheritance for this condition. These include deletion of an imprinted gene; combinatorial interplay between the 8q21 micro deletion and additional, unidentified genetic variants; or autonomous domains within the 8q21 region that partition differentially-expressed genes into distinct chromatin loops.

IMPAD1 TESTING IN SOME CATEL-MANZKE SYNDROME PATIENTS URGED

Patients with growth retardation, cleft palate with micrognathia, knee dislocation, accessory bones in hands and feet with abnormally shaped phalanges, and carpal synostosis should have IMPAD1 testing, Nizon et al. write (p. 2183, DOI: 10.1002/ajmg.a.35504).

Catel–Manzke syndrome (CMS) involves hyperphalangism with bilateral deviation of the index fingers and micrognathia, with or without cleft palate. Some atypical cases have other malformations.

CMS has features that overlap with those of Desbuquois dysplasia type 1 due to calcium-activated nucleotidase 1 (CANT1) mutations, and with chondrodysplasia with joint dislocations, gPAPP type, due to inositol monophosphatase domain containing 1 (IMPAD1) mutations, previously reported in four patients. They all had short stature, joint dislocations, brachydactyly, and cleft palate.

Nizon et al. screened five new patients with CMS for CANT1 andIMPAD1 mutations. Three were diagnosed as classical CMS patients and two as Catel–Manzke-like patients, based on the presence of additional features.

The researchers identified two homozygous loss-of-function IMPAD1 mutations in the Catel–Manzke-like patients. Their phenotype included severe growth retardation with short and abnormal extremities, cleft palate with micrognathia, and knee hyperlaxity. Radiographs of these patients' hands and feet revealed numerous accessory bones with abnormally shaped phalanges and carpal synostosis.

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Figure 1 Clinical and radiological features of IMPAD1 mutated Patient 1 (p.Arg187X). Note the disproportionate short stature with short hands and feet, pectus excavatum, bilateral genu valgum, and facial dysmorphism.

WOMEN WITH EHLERS–DANLOS SYNDROME CAN SAFELY DELIVER BABIES BUT MAY NEED SPECIAL CARE

Because pelvic pain plagues nearly all pregnant women with joint hypermobility syndrome (JHS), also known as Ehlers–Danlos syndrome hypermobility type (EDS-HT), they need special care to prevent symptoms from worsening during pregnancy and delivery and upon receiving anesthesia, write Castori et al. (p. 2176, DOI: 10.1002/ajmg.a.35506).

In their analysis of obstetric and gynecological features of 82 Italian women with JHS/EDS-HT attending two centers, the authors found a total of 93 diagnosed conceptions, which resulted in term deliveries in 66.7% of cases. These deliveries had good outcomes, with no stillbirth or hypoxic or ischemic events. Researchers noted vaginal delivery in 72.2%, vacuum use in 5.5%, and cesarean section in 22.3%. In 17 pregnancies, anesthesia use involved no problems.

Major postpartum complications included abnormal scar formation after cesarean or episiotomy (46.1%), hemorrhage (19.4%), pelvic prolapses (15.3%), deep venous thrombosis (4.2%), and coccyx dislocation (1.4%). Prolapses were the most clinically relevant complication and associated with episiotomy. The authors suggest avoiding episiotomy and considering elective cesarean section, especially in the presence of instrumentally confirmed dysautonomia.

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Figure 3 A composite photograph of the subjects of this report.

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