Frenotomy for tongue-tie (frenulum linguae breve) showed improved symptoms in the short- and long-term follow-up.

AIM: To evaluate clinical manifestations of tongue-tie as well as short-term and long-term outcomes following frenotomy. METHODS: In this retrospective study, for 329 patients (295 infants and 34 children) who underwent frenotomy between 2011 and 2017, symptoms, short-term and long-term outcomes were evaluated. RESULTS: Of the 295 infants (median age six weeks), 199 (=60%) showed inadequate breastfeeding. Symptoms were painful or sore maternal nipples, poor weight gain, dribbling milk from the corner of the mouth, reduced milk supply, inadequate latch during bottle-feeding and maternal mastitis. In the 34 children, predominant symptoms were articulation disorders, misaligned teeth and problems with swallowing solid food. Of the 141 patients with short-term feedback, 86% reported improvement, 13% an unchanged situation. In a former premature, the reported worsening of symptoms ('breath spells') are likely related to prematurity. Of the 164 patients where the questionnaire for long-term outcome was provided, 82% reported improvement, 16% an unchanged situation. For two infants worsening was reported, referring to refusal to drink from breast or bottle for two hours after the procedure and fever for one day, respectively. CONCLUSION: Frenulum breve is a potential cause of breastfeeding difficulties and can be treated safely and efficiently by frenotomy.

A recurrent germline mutation in the PIGA gene causes Simpson-Golabi-Behmel syndrome type 2.

Hypomorphic germline mutations in the PIGA (phosphatidylinositol glycan class A) gene recently were recognized as the cause of a clinically heterogeneous spectrum of X-linked disorders including (i) early onset epileptic encephalopathy with severe muscular hypotonia, dysmorphism, multiple congenital anomalies, and early death ("MCAHS2"), (ii) neurodegenerative encephalopathy with systemic iron overload (ferro-cerebro-cutaneous syndrome, "FCCS"), and (iii) intellectual disability and seizures without dysmorphism. Previous studies showed that the recurrent PIGA germline mutation c.1234C>T (p.Arg412*) leads to a clinical phenotype at the most severe end of the spectrum associated with early infantile lethality. We identified three additional individuals from two unrelated families with the same PIGA mutation. Major clinical findings include early onset intractable epileptic encephalopathy with a burst-suppression pattern on EEG, generalized muscular hypotonia, structural brain abnormalities, macrocephaly and increased birth weight, joint contractures, coarse facial features, widely spaced eyes, a short nose with anteverted nares, gingival overgrowth, a wide mouth, short limbs with short distal phalanges, and a small penis. Based on the phenotypic overlap with Simpson-Golabi-Behmel syndrome type 2 (SGBS2), we hypothesized that both disorders might have the same underlying cause. We were able to confirm the same c.1234C>T (p.Arg412*) mutation in the DNA sample from an affected fetus of the original family affected with SGBS2. We conclude that the recurrent PIGA germline mutation c.1234C>T leads to a recognizable clinical phenotype with a poor prognosis and is the cause of SGBS2.

Clinical aspects of Hyaline Fibromatosis Syndrome and identification of a novel mutation.

BACKGROUND: Hyaline fibromatosis syndrome is an autosomal recessive disease caused by mutations in ANTXR2 which leads to loss of function of the transmembrane protein anthrax toxin receptor 2. It is distinguished by characteristic skin lesions, gingival hyperplasia, joint and bone disease, and systemic involvement. METHODS: Based on the case of an 11-year-old female patient with typical features of hyaline fibromatosis syndrome and the underlying pathogenic compound heterozygote variants in ANTXR2 we discuss the genetic and clinical aspects of hyaline fibromatosis syndrome. RESULTS: The novel mutation in ANTXR2 (c.1223T>C, p.Leu408Pro variant) seems to allow for a protracted course of the disease. CONCLUSION: Our findings add to the phenotypic, genetic, and biochemical spectrum of hyaline fibromatosis syndrome.

Variable expressivity of TCTEX1D2 mutations and a possible pathogenic link of molar-incisor malformation to ciliary dysfunction.

OBJECTIVE: Clarification of the molecular basis of a ciliopathy associated with molar-incisor malformation in a consanguineous Turkish family. DESIGN: Full dental and clinical examinations, histologic analysis, comprehensive genetic analyses including exome sequencing, ciliary function tests and transmission electron microscopy of ciliary biopsies in the surviving patient. RESULTS: Two siblings had situs inversus and complex heart defects suggestive of ciliary dysfunction. The affected girl who died in utero showed severe chest abnormalities compatible with Jeune syndrome which were not present in the affected boy. Dental investigations in the boy showed typical signs of molar-incisor-malformation. Exome sequencing identified a homozygous intragenic deletion in TCTEX1D2 which is predicted to completely remove protein function. Ciliary function tests and electron microscopy showed mild irregularities of motile cilia such as compound cilia and loss of membranes. CONCLUSIONS: Our findings support the suggestion that TCTEX1D2 mutations have variable expressivity and may be associated with disturbances of embryonic development caused by both, ciliary signaling and motile dysfunction. The presence of molar-incisor-malformation in the living patient raises the possibility of a pathogenetic link of this rare dental anomaly to ciliary dysfunction during tooth development at least in some individuals.