Beals syndrome or congenital contractual arachnodactyly is a rare disorder characterized by multiple joint contractures, Marfanoid body habitus and crumpled ears and has been associated with scoliosis. This study reports a clinical series of patients with Beals syndrome who have had surgical treatment for their spinal deformity. A retrospective review of all patients at a single institution who had a genetically-confirmed diagnosis of Beals syndrome and had surgical treatment for their scoliosis were reviewed for surgical outcome and complications. There were eight patients who had surgery at an average age of 11.5 years, four were female and four had cardiovascular abnormalities requiring treatment. The preoperative coronal Cobb was 82.3° which improved to 42.1°(46.8% correction), and 46.5° (43.5% correction) at final follow-up. Preoperative halo-gravity-traction was used in three patients. Three patients had a posterior instrumentation and fusion (PSFI), 2 a combined anterior/PSFI, 1 had tethering, 1 with PSFI with posteriorly-approached discectomy, and 1 with a PSFI and vertebral column resection. One of the eight patients had a critical intraoperative neuromonitoring event but was normal following appropriate responses and no patient awoke with neurologic deficits. Two had an unplanned return to the operating room for implant dislodgement and each had a successful revision. Scoliosis associated with Beals syndrome can have large curves at the time of surgery and require a variety of surgical approaches to achieve a good result. Revision surgery with return to the operating room is necessary in 25% of patients.

Multiple endocrine neoplasia type 2 syndrome (MEN2) is a hereditary disease resulting from mutations of the rearranged during transfection (RET) protooncogene subclassified into MEN2A [medullary thyroid carcinoma (MTC), pheochromocytoma, and primary hyperparathyroidism] and MEN2B (MTC, pheochromocytoma, Marfanoid habitus, mucous neuromas, and intestinal ganglioneuromatosis). Prophylactic thyroidectomy is recommended in RET-mutated patients. The age at which it should be performed depends on the type and aggressiveness of the mutation. This study aimed to evaluate the genotype/phenotype correlation and outcome in pediatric/adolescent carriers of MEN2 RET mutation. In a retrospective series of 23 carriers of RET MEN2 mutation who were ≤19 years old at diagnosis and had undergone total thyroidectomy ± lymphadenectomy, the following were analyzed: 1) specific RET mutation, 2) clinical and histopathological characteristics, 3) genotype/phenotype correlation, and 4) outcome at last follow-up. In our series, the female gender was more prevalent (F/M ratio 2.8/1), and the median age was 14.9 years [interquartile range (IQR) 12.6-17.2]. RET mutations were at very high risk in 4.3% of patients (M918T), high risk in 43.5% (C634), and moderate risk in 52.2% (47.8% C618 and 4.3% C620). All patients underwent surgery: at histology, MTC was found in 19/23 (82.6%) patients, C-cell hyperplasia in 2/23 (8.7%), and benign histology in 2/23 (8.7%). Ten patients (52.6%) had a disease event during the follow-up: 2/19 (10.5%) showed biochemical disease, 6/19 (31.6%) lymph node recurrences, and 2/19 (10.5%) distant metastases (50% liver, 50% bone). At the last follow-up, nine MTCs were not cured. One patient died after 9 years of follow-up at 21 years old (M918T RET+). From these data, it is clear to see the importance of genetic counseling and RET screening in all first-degree relatives of patients with proven MEN2. The goal should be to subject patients to surgery for prophylactic and not curative purposes, i.e., before the onset of MTC, given the high risk of persistent or recurrent disease also in pediatric/adolescent patients.

We have previously reported on a consanguineous family where 2 siblings, a girl and a boy, presented with tall stature, long and triangular faces, prominent forehead, telecanthus, ptosis, everted lower eyelids, downslanting palpebral fissures, large ears, high arched palate, long arm span, arachnodactyly, advanced bone age, joint laxity, pectus excavatum, inguinal hernia, and myopia, suggestive of a new subtype of connective tissue disorder (Megarbane et al. AJMG, 2012; 158(A)5: 1185-1189). On clinical follow-up, both patients had multiple inguinal, crural, and abdominal herniae, intestinal occlusions, several huge diverticula throughout the gut and the bladder, and rectal prolapse. In addition, the girl had a mild hearing impairment, and the boy a left diaphragmatic hernia. Here we describe the molecular characterization of this disorder using Whole Exome Sequencing, revealing, in both siblings, a novel homozygous missense variant in the EFEMP1 gene, c.163T > C; p.(Cys55Arg) whose homozygous by descent, autosomal recessive transmission was confirmed through segregation analysis by Sanger sequencing. In addition, the girl exhibited a homozygous mutation in the MYO3A gene, c.1370_1371delGA; p.(Arg457Asnfs*25), associated with non-syndromic deafness. The siblings were also found to harbor a homozygous nonsense variant in the VCPKMT gene. We review the literature and discuss our updated clinical and molecular findings that suggest EFEMP1 to be the probable candidate gene implicated in this novel connective tissue disease.

In Marfan syndrome early impairment of left ventricular systolic function has been reported. Our aim was to evaluate the left ventricular systolic function in young adults with Marfanoid habitus (MH) (includes arachnodactylia, dolichostenomelia, high palate, deformations of the thorax). We studied 137 young subjects (mean age 21.3±1.5) - 58 male, 79 female. Transthoracic echocardiography (Vivid 7 Dimension, GE) was performed in 24 asymptomatic MH with excluded Marfan syndrome and 42 healthy control subjects. Radial and circumferential systolic strain and strain rate were determined using spackle tracking (EchoPAC»08, GE). Ascending aorta diameters were larger in subjects with MH. LV mass index did not differ significantly between groups, but interventricular septum and posterior wall thickness were greater in MH group. Local LV radial and circumferential systolic deformation indices were significant decreased in MH group. Young adults with MH in the absence of major findings of Marfan syndrome (ascending aortic aneurysm and ectopia lentis) have decreased LV systolic function.