Three novel mutations of the MCT8 (SLC16A2) gene: individual and temporal variations of endocrinological and radiological features.

We performed genetic analysis and clinical investigations for three patients with suspected monocarboxylate transporter 8 (MCT8) deficiency. On genetic analysis of the MCT8(SLC16A2) gene, novel mutations (c.1333C>A; p.R445S, c.587G>A; p.G196E and c.1063_1064insCTACC; p.R355PfsX64) were identified in each of three patients. Although thyroid function tests (TFTs) showed the typical pattern of MCT8 deficiency at the time of genetic diagnosis in all patients, two patients occasionally were euthyroid. A TRH test revealed low response, exaggerated response and normal response of TSH, respectively. Endocrinological studies showed gonadotropin (Gn) deficiency in two adult patients. On ultrasonography, goiter was detected in one patient. Interestingly, pituitary magnetic resonance imaging (MRI) demonstrated atrophy and thinness of the pituitary gland in two patients. Our findings suggest that thyroid status in patients with MCT8 deficiency varies with time of examination, and repeated TFTs are necessary for patients suspected of MCT8 deficiency before genetic analysis. In addition, it is noteworthy that some variations were observed on the TRH test and ultrasonography of the thyroid gland in the present study. Morphological abnormality of the pituitary gland may be found in some patients, while Gn deficiency should be considered as one of the complications.

[Safety and efficacy of surgical closure of the larynx for recurrent aspiration pneumonia in persons with severe motor and intellectual disabilities: a comparative study with tracheoesophageal diversion].

OBJECTIVE: We retrospectively investigated the efficacy and complications of surgical closure of the larynx (SCL) for recurrent aspiration pneumonia in comparison with tracheoesophageal diversion. METHODS: The subjects were persons with severe motor and intellectual disabilities (SMID) who had undergone surgery for recurrent aspiration pneumonia between 1994 and 2011: A 8 SCL patients group and a 16 tracheoesophageal diversion patients group. We investigated two groups the lower respiratory infection incidence, length of hospital stay for the surgery, postoperative complications, and rate of cannula withdrawal, by reviewing medical records. RESULTS: Both the SCL and the tracheoesophageal diversion group showed a reduction in the incidence of infection after surgery, indicating that the efficacy of SCL was equivalent to that of tracheoesophageal diversion in preventing aspiration pneumonea. The SCL group showed a reduction in the length of hospital stay and an increased rate of cannula withdrawal as compared with the tracheoesophageal diversion group. CONCLUSION: The efficacy of SCL was equivalent to that of tracheoesophageal diversion in preventing aspiration for SMID. We consider SLC to have potential for reducing the burden on patients.

Epilepsy and neurological findings in 11 individuals with 1p36 deletion syndrome.

The 1p36 deletion syndrome is a newly delineated multiple congenital anomalies/mental retardation syndrome characterized by mental retardation, growth delay, epilepsy, congenital heart defects, characteristic facial appearance, and precocious puberty. We analyzed 11 patients by fluorescence in situ hybridization (FISH) using commercially available bacterial artificial chromosome and P1-derived artificial chromosome genomic clones to define the chromosomal deletion responsible for the 1p36 deletion syndrome. Cytogenetic investigation revealed two cases with a terminal deletion of 1p36. Nine patients had an apparently normal karyotype with standard G-bands by trypsin using Giemsa (GTG), but FISH screening with the highly polymorphic genetic marker D1Z2, which is mapped to 1p36.3 and contains an unusual reiterated 40-bp variable number tandem repeat, revealed a submicroscopic deletion. All patients had severe to profound mental retardation. Based on the University of California Santa Cruz Genome Browser, we constructed a deletion map and analyzed the relationship between neurological findings and chromosomal deletions for the 11 cases. Six cases had intractable epilepsy and three had no seizures. The common deletion interval was about 1 million base pairs (Mbp) located between RP11-82D16 and RP4-785P20 (Rho guanine exchange factor (GEF) 16). The severity of clinical symptoms correlates with the size of the deletion. This is demonstrated by the 3 patients with at least 8Mbp deletions that display profound mental retardation and congenital heart defects. Although haploinsufficiency of the potassium channel beta-subunit (KCNAB2) is thought to be responsible for intractable seizures in the 1p36 deletion syndrome, this was not the case for 3 of the 11 patients in this study. Further investigation of the 1p36 region is necessary to allow identification of genes responsible for the 1p36 deletion syndrome.

Further delineation of the behavioral and neurologic features in Costello syndrome.

To describe clinical and neurodevelopmental phenotypes of Costello syndrome, we performed a retrospective review of the clinical records and findings in 10 children with Costello syndrome. All patients showed significant postnatal growth retardation and severe feeding difficulties leading to failure to thrive from early infancy. All required tube feeding and some needed high-calorie formulas for variable periods. Developmental quotients/IQs in seven children were 50 or less, and three were in the mildly retarded range. Five had seizures. Remarkable manifestations not previously reported were the characteristic behavior in infancy. Although happy and sociable personality was always emphasized in the genetic literature, all children showed significant irritability, including hypersensitivity to sound and tactile stimuli, sleep disturbance, and excess shyness with strangers in infancy. Those symptoms usually disappeared around age 2-4 years. Other clinical signs included cardiac abnormalities (8), musculoskeletal abnormalities (10), ophthalmological manifestations (5), increased urinary vanillymandelic acid (VMA) and homovanillic acid (HVA) (3), rhabdomyosarcoma (1), laryngomalacia (1), and cryptorchidism (1). Only three girls had papillomata. Family histories were negative for Costello syndrome. In conclusion, we confirm the wide spectrum of mental function in patients with Costello syndrome, which ranges from severe to mild. During infancy Costello syndrome showed remarkable irritability with severe feeding problems, which attributes significant difficulties to the parents of affected children.

Patellar dislocation in Kabuki syndrome.

We describe four individuals (two females and two males) with Kabuki syndrome and recurrent dislocation of the patella. The age of diagnosis of patellar dislocation ranged from 11 to 23 years. One individual underwent excision of the free fragment and transfer of the tibial tuberosity with good outcome. Two required patellar brace for instability. Characteristics of individuals with the syndrome at a high risk of patellar dislocation include female, adolescence or young adulthood, joint laxity, and obesity.