Identification of novel homozygous variants in FOXE3 and AP4M1 underlying congenital syndromic anophthalmia and microphthalmia.

BACKGROUND: Anophthalmia and microphthalmia are severe developmental ocular disorders that affect the size of the ocular globe and can be unilateral or bilateral. The disease is found in syndromic as well as non-syndromic forms. It is genetically caused by chromosomal aberrations, copy number variations and single gene mutations, along with non-genetic factors such as viral infections, deficiency of vitamin A and an exposure to alcohol or drugs during pregnancy. To date, more than 30 genes having different modes of inheritance patterns are identified as causing anophthalmia and microphthalmia. METHODS: In the present study, a clinical and genetic analysis was performed of six patients with anophthalmia and microphthalmia and/or additional phenotypes of intellectual disability, developmental delay and cerebral palsy from a large consanguineous Pakistani family. Whole exome sequencing followed by data analysis for variants prioritization and validation through Sanger sequencing was performed to identify the disease causing variant(s). American College of Medical Genetics and Genomics (ACMG) guidelines were applied to classify clinical interpretation of the prioritized variants. RESULTS: Clinical investigations revealed that the affected individuals are afflicted with anophthalmia. Three of the patients showed additional phenotype of intellectual disability, developmental delays and other neurological symptoms. Whole exome sequencing of the DNA samples of the affected members in the family identified a novel homozygous stop gain mutation (NM_012186: c.106G>T: p.Glu36*) in Forkhead Box E3 (FOXE3) gene shared by all affected individuals. Moreover, patients segregating additional phenotypes of spastic paraplegia, intellectual disability, hearing loss and microcephaly showed an additional homozygous sequence variant (NM_004722: c.953G>A: p.Arg318Gln) in AP4M1. Sanger sequencing validated the correct segregation of the identified variants in the affected family. ACMG guidelines predicted the variants to be pathogenic. CONCLUSIONS: We have investigated first case of syndromic anophthalmia caused by variants in the FOXE3 and AP4M1. The present findings are helpful for understanding pathological role of the mutations of the genes in syndromic forms of anophthalmia. Furthermore, the study signifies searching for the identification of second variant in families with patients exhibiting variable phenotypes. In addition, the findings will help clinical geneticists, genetic counselors and the affected family with respect to prenatal testing, family planning and genetic counseling.

Couching of cataractous lens in microphthalmic eyes with irido-fundal coloboma: revisiting the historical technique.

PURPOSE: Cataract surgery in microphthalmic eyes is challenging due to anatomical restraints, hard bulky nucleus. This series aims to evaluate the safety and efficacy of couching of intraocular lens in irido-fundal coloboma with microphthalmos. SETTING: Tertiary care centre in South India. DESIGN: Retrospective non-comparative study in eyes with irido-fundal coloboma, corneal diameter < 7 mm and brown cataract. Visual acuity less than 6/60 in other eye. METHODS: Anterior chamber entry made, zonules broken and lens dislocated into the vitreous cavity in a controlled manner. Baseline Clinico-demographic details, corrected distance visual acuity (CDVA), Intra-ocular pressure (IOP), corneal diameter, axial length, lens status and post-surgery CDVA, IOP and complications recorded and followed up for atleast 6 months. RESULTS: Fifteen eyes of 15 subjects were evaluated with a mean age 49.4 ± 10.9 years. At baseline, mean IOP 14.5 ± 3.8 mmHg, mean axial length 19.3 ± 0.5 mm, mean corneal diameter was 6.5 ± 0.34 mm and CDVA 2 logMAR which improved to 1.5 logMAR at 3 months (p value 0.002). Transient spike in IOP in 33.3% subjects was medically managed with no significant difference in IOP (p > 0.05) at baseline (14.5 ± 3.8 mmHg), 3 months post-surgery (16 ± 2.8 mmHg) and 6 months post-surgery (14.9 ± 2.5 mmHg). One patient underwent re-couching. No other major complications were noted. CONCLUSION: Couching of cataractous lens is an effective and safe method in microphthalmic eyes with irido-fundal coloboma as last resort procedure, where no other surgical procedure may work. It provides an ambulatory gain of visual acuity in previously non-ambulatory subjects. Corneal measurements help in determining the subset of patients where couching offers viable option.

Variable phenotype of secondary congenital corneal opacities associated with microphthalmia with linear skin defects syndrome.

To describe the anterior segment (AS) findings in patients with microphthalmia with linear skin defects syndrome (MLS), also known as microphthalmia, dermal aplasia, and sclerocornea (MIDAS). A retrospective chart review was conducted to identify patients with a diagnosis of MLS syndrome seen at UPMC Children's Hospital of Pittsburgh. Ophthalmic examination, high-frequency ultrasound, AS optical coherence tomography, and molecular testing were reviewed. Five female patients (10 eyes) were identified. One eye was anophthalmic, one was in a status post penetrating keratoplasty, and eight eyes presented with congenital corneal opacity (CCO). Of these, one showed a normal lens and a very small faint CCO; five showed congenital aphakia and characteristic silvery appearance of the cornea with vascularization; and two showed irido-corneal adhesions in association with normal or abnormal lens and localized avascular CCO. Genetic testing was performed and revealed involvement of HCCS in four patients. In MLS patients, kerato-irido-lenticular dysgenesis can be associated with secondary CCO. It is important to distinguish these CCO from sclerocornea, in order to refine the appropriate management and counseling the parents about the prognosis.

SOX2 pathogenic variants with normal eyes: Expanding the phenotypic spectrum.

SOX2 pathogenic variants, though rare, constitute the most commonly known genetic cause of clinical anophthalmia and microphthalmia. However, patients without major ocular malformation, but with multi-system developmental disorders, have been reported, suggesting that the range of clinical phenotypes is broader than previously appreciated. We detail two patients with bilateral structurally normal eyes along with 11 other previously published patients. Our findings suggest that there is no obvious phenotypic or genotypic pattern that may help set apart patients with normal eyes. Our patients provide further evidence for broadening the phenotypic spectrum of SOX2 mutations and re-appraising the designation of SOX2 disorder as an anophthalmia/microphthalmia syndrome. We emphasize the importance of considering SOX2 pathogenic variants in the differential diagnoses of individuals with normal eyes, who may have varying combinations of features such as developmental delay, urogenital abnormalities, gastro-intestinal anomalies, pituitary dysfunction, midline structural anomalies, and complex movement disorders, seizures or other neurological issues.

First implication of MIP in bilateral microphthalmia with persistent fetal vasculature.

Persistent fetal vasculature (PFV) is a rare malformative ocular disorder resulting from the failure of the hyaloid vasculature to regress. The severity of the visual impairment is depending on the underlying eye defects, ranging from discreet hyaloid remnants to severe ocular anomalies. Although PFV is generally unilateral, sporadic and idiopathic, a genetic cause has been described in some individuals, especially those presenting with a bilateral and/or syndromic form of PFV. The genes occasionally described in PFV are most often responsible for a wide spectrum of ocular phenotypes such as ATOH7 or NDP, a gene also known to be involved in Norrie disease, a X-linked vitreoretinopathy with extra-ocular features. We describe here a patient with an ocular phenotype consisting in non-syndromic bilateral PFV with cataract and microphthalmia, in whom a recurrent heterozygous de novo MIP disease-causing variant was detected after using a dedicated 119-ocular genes panel approach. Defects in the MIP gene are classically associated with dominant non-syndromic congenital cataract without other ocular malformative features. Thus, this case highlights the value of exploring individuals with PFV, even those with non-syndromic forms. It also broadens the phenotypic spectrum of the MIP gene, adding new insights into the gene networks underlying PFV pathophysiology, that remains unclear.

Retinitis pigmentosa and nanophthalmos in a patient with attenuated Hunter's syndrome.

PURPOSE: To describe a case of retinitis pigmentosa and nanophthalmos in a patient with attenuated Hunter's syndrome. METHODS: Fundus photography, total field electroretinogram, ultrasound, computerized visual field examination, biochemical examination and genetic testing were obtained. RESULTS: The fundus exam showed diffuse arteriolar attenuation, optic disc with regular contours, and pigment agglomerates like "bone spicules" in the middle periphery. Ultrasound examination revealed scleral thickening and short axial diameter in both eyes. The total field electroretinogram exam showed a subnormal result with greater impairment of the scotopic phase of the exam. Computerized visual field examination demonstrated a diffuse reduction in retinal sensitivity in the periphery. Biochemical examination showed increased urine glycosaminoglycan excretion and iduronate-2-sulphatase activity (IDS) deficiency in leukocytes, confirming the type II mucopolysaccharidosis. Molecular analysis revealed a novel missense mutation (p.A77D) in the IDS gene. CONCLUSION: The case report is about a patient presented an attenuated form of the syndrome, with no cognitive impairment. Ophthalmologic follow-up is still an important part of multidisciplinary treatment for Hunter's syndrome.

Topical brimonidine induced acute uveal effusion in a patient with nanophthalmos: a case report.

BACKGROUND: We report a case of uveal effusion in a nanophthalmic eye after topical use of brimonidine. CASE PRESENTATION: A 42-year-old male patient with nanophthalmos experienced sudden blurred vision in the right eye after using topical brimonidine when picking up tennis balls repeatedly 6 weeks after bilateral YAG peripheral iridotomy. Ocular examination showed wide choroidal and exudative retinal detachment in the temporal and inferior region, involving the macula. Acute uveal effusion in the right, bilateral nanophthalmos was diagnosed. Oral and topical corticosteroids, combined with topical nonsteroids and atropine led to a complete resolution of the uveal effusion after one month. CONCLUSION: This case suggested a possible causal relationship between the topical use of brimonidine and acute uveal effusion in patients with nanophthalmos. Topical brimonidine should be used with caution in nanophthalmic eyes.

A unique case of bilateral nanophthalmos and pigmentary retinal abnormality with unilateral angle closure glaucoma and optic disc pit.

BACKGROUND: Microophthalmos or 'dwarf eye' is characterized by an axial length 2 standard deviation less than age-matched controls. It is classified into nanophthalmos, relative anterior microphthalmos, and posterior microphthalmos based on the anterior segment: posterior segment ratio. Nanophthalmos can occur in association with optic disc drusen, foveoschisis, and retinitis pigmentosa, as an autosomal recessive syndrome linked to mutations in the MFRP gene. We report a case of bilateral nanophthalmos and pigmentary retinopathy with angle closure glaucoma and optic disc pit in one eye. We believe this to be the first case presenting with optic disc pit in association with nanophthalmos. CASE PRESENTATION: A 56-year-old female presented with bilateral small eyes, high hypermetropia, shallow anterior chamber depth, increased lens thickness, mid-peripheral retinal flecks, and macular edema. She also had high intraocular pressure in the right eye, with a disc cupping of 0.9 with an Optic disc pit. The macular edema in the right eye was found to occur in association with the Optic disc pit, whereas, in the left eye, it was associated with intra-retinal hemorrhages and diagnosed as macular branch retinal vein occlusion secondary to hypertension. She was started on anti-glaucoma medications in both eyes and planned for Anti-VEGF injection in the left eye. CONCLUSION: This case report is unique as it reports an association of Nanophthalmos with Optic Disc pit, with an associated angle closure glaucoma in the same eye, an association which has never been previously reported in the literature.

Variants of BEST1 and CRYBB2 cause a complex ocular phenotype comprising microphthalmia, microcornea, cataract, and vitelliform macular dystrophy: case report.

BACKGROUND: Best vitelliform macular dystrophy (BVMD), caused by pathogenic variants of the BEST1 gene, has not been reported in association with cataracts and ocular malformations. We reported a case with a complex ocular phenotype comprising microphthalmia, microcornea, cataract, and vitelliform macular dystrophy. CASE PRESENTATION: A six-year-old girl manifested photophobia and a poor visual behavior. A thorough ophthalmic examination revealed the patient to have bilateral microphthalmia, microcornea, congenital cataract, and Best vitelliform macular dystrophy (BVMD). Whole exome sequencing (WES) identified one variant in the BEST1 and one variant in CRYBB2 genes: c.218 T > G p.(Ile73Arg) and c.479G > C p.(Arg160Pro). The first variant was inherited from the proband's father, who was diagnosed with subclinical BVMD, while the second was a de novo variant. A minigene assay showed that c.218 T > G in BEST1 did not affect pre-mRNA splicing. CONCLUSIONS: This case suggests that the complex ocular phenotype comprising BVMD and congenital cataract with microphthalmia cannot be explained by variation in one gene but is caused by variants in BEST1 and CRYBB2. This case highlights the importance of general clinical evaluation and comprehensive genetic testing for diagnosing complex eye diseases.

Coloboma Accompanying Microphthalmos With Orbital Cyst in a Mother and Child.

Microphtalmos with orbital cyst is a rare congenital abnormality of the eye and orbit that is caused by incomplete closure of the embryonic fissure. The cysts project through in a coloboma of the affected eye. It may be sporadic or genetic. Herein, the authors present a 32-year-old mother with unilateral and her 4-month-old daughter with bilateral microphtalmos and accompanying orbital cyst.

Long-read genome sequencing resolves a complex 13q structural variant associated with syndromic anophthalmia.

Microphthalmia, anophthalmia, and coloboma (MAC) are a heterogeneous spectrum of anomalous eye development and degeneration with genetic and environmental etiologies. Structural and copy number variants of chromosome 13 have been implicated in MAC; however, the specific loci involved in disease pathogenesis have not been well-defined. Herein we report a newborn with syndromic degenerative anophthalmia and a complex de novo rearrangement of chromosome 13q. Long-read genome sequencing improved the resolution and clinical interpretation of a duplication-triplication/inversion-duplication (DUP-TRP/INV-DUP) and terminal deletion. Sequence features at the breakpoint junctions suggested microhomology-mediated break-induced replication (MMBIR) of the maternal chromosome as the origin. Comparing this rearrangement to previously reported copy number alterations in 13q, we refine a putative dosage-sensitive critical region for MAC that might provide new insights into its molecular etiology.

Posterior microphthalmos with achievement of good visual acuity and disappearance of papillomacular retinal folds: a case report.

BACKGROUND: Posterior microphthalmos (PM) is a rare condition with poor visual prognosis even after amblyopia treatment. We report a case of PM with achievement of good visual acuity and disappearance of papillomacular retinal folds (PFs) over a period of 7 years. CASE PRESENTATION: A girl aged 3 years and 5 months was referred to our hospital, after poor visual acuity was identified at a medical checkup for 3-year-olds. She had severe spherical hyperopia: + 17.25 D in the right eye (RE) and + 18 D in the left eye (LE). Her corrected visual acuity was 20/200 in the RE and 20/250 in the LE. PFs were observed in both eyes on optical coherence tomography (OCT), and the diagnosis of PM was made based on the normal corneal diameter and anterior chamber depth. During the course of the disease, a gradual decrease in the height of the PFs was observed on OCT. The corrected visual acuity at age 10 years was 20/20 in the RE and 20/25 in the LE. CONCLUSIONS: The visual prognosis of PM is poor, and only one case with good visual acuity has been reported in the literature. The patient in the present case not only developed good visual acuity, but also showed improvement in macular morphology, which was not noted in previous reports. Early diagnosis of PM and early amblyopia treatment is important for the visual development in PM.

Unilateral buphthalmos, corneal staphyloma and corneal fistula caused by pathogenic variant in the PITX3 gene: a case report.

INTRODUCTION: PITX3 has been reported to be associated with congenital cataracts, anterior segment mesenchymal dysgenesis, Peters' anomaly, and microphthalmia. In this case, an infant with unilateral buphthalmos, corneal staphyloma and corneal fistula carrying a variant in PITX3 was reported. CASE DESCRIPTION: We describe a 4-month-old female infant who was referred to our Eye Clinic because of gradual enlargement of the eyeball in the right eye and whitish opacity in both eyes. Buphthalmos with long axial length (22.04 mm), macrocornea with diffuse corneal oedema and opacity (14.50 mm*14.50 mm) and high intraocular pressure (23.78 mmHg) were detected in the right eye. Microphthalmia with short axial length (16.23 mm), microcornea with diffuse corneal oedema and opacity (7.50 mm*6.50 mm) were detected in the left eye. A 360° trabeculotomy was performed for the right eye. However, corneal staphyloma and corneal fistula in the right eye were detected 6 months after the surgery. A variant in exon 4 of PITX3 (c.640_656dup (p. Gly220Profs*95)) was identified in the proband but was not detected in her healthy parents. CONCLUSION: A novel phenotype characterized by unilateral buphthalmos, corneal staphyloma and corneal fistula in an infant were reported to be associated with PITX3 in our study. Our study expands the scope of the clinical heterogeneity of PITX3 variants. It also improves our understanding and increases the attention given to patients with PITX3 variants.

A novel deletion mutation in the BCOR gene is associated with oculo-facio-cardio-dental syndrome: a case report.

BACKGROUND: Oculo-facio-cardio-dental syndrome is a rare X-linked dominant syndrome, characterized by radiculomegaly, congenital cataracts, dysmorphic facial features, and congenital heart disease. Because of the rarity, this syndrome could be misdiagnosed by the clinician, especially for the infant who may present only one to two systems involved. CASE PRESENTATION: Here we report a 3-month-old female infant presenting with typical clinical manifestations of oculo-facio-cardio-dental syndrome, like ocular, facial, cardiac, and skeletal abnormalities, and the genetic analyses of the proband and her parents were provided. Genetic evaluations were completed using whole exon sequencing, which revealed a novel heterozygous mutation between exons 7 and 14 of the BCOR gene(OMIM:300485) in this patient but not in her parents. This mutation is likely to encode a premature stop codon producing a truncated protein. Our patient was diagnosed early enough to allow for the cardiac defects to be treated first, and she will be closely followed up to ensure that any new presentations are treated in a timeous manner. CONCLUSION: This patient fits the diagnostic criteria for oculo-facio-cardio-dental syndrome and is the youngest oculo-facio-cardio-dental syndrome patient ever reported, which is most important for her prognosis. In addition, this manuscript also describes a novel potenitally causative mutation for this syndrome.

Therapeutic Strategies in 103 Children with Congenital Microphthalmos. / Therapiestrategien bei 103 Kindern mit kongenitalem Mikrophthalmus.

INTRODUCTION: Congenital microphthalmos can either occur alone (simple microphthalmos) or be associated with other ocular malformations, such as sclerocornea or cataract (complex microphthalmos). As this is a rare condition, there are no uniform recommendations for treatment. MATERIAL AND METHODS: Retrospective case series of 103 patients or a total of 114 eyes with congenital microphthalmos, with reporting of age, sex, visual acuity, pupil reaction, axial length, horizontal width of the palpebral fissure, type of therapy performed and complications. RESULTS: All patients would have been able to be fitted with a prosthesis primarily. The size of the palpebral fissure depended on the underlying findings: "bilateral microphthalmos" < "microphthalmos and healthy fellow eye" < "microphthalmos and fellow anophthalmos". In order to assess visual (residual) function in an infant in the first weeks or months of life, the pupillary response is of the upmost importance in deciding on therapy, especially in unilateral disease, and as assessed with the indirect light response of the healthy eye. In about half of the cases, conservative prosthetic treatment was sufficient. After the successful initial fitting of a prosthesis, the prosthesis was enlarged according to the ocularist's instructions. If the eye length difference was so large that symmetry could not be achieved even with a double-walled prosthesis, volume filling with retrobulbar implanted self-swelling pellet expanders (osmed GmbH, Ilmenau) was offered. In almost one third of the patients, no surgical therapy or prosthetic treatment was performed. The reason for this was usually the presence of minimal visual function of the microphthalmos - ranging from light perception to hand movements. CONCLUSIONS: In the case of visual function of the microphthalmos, surgical measures should not be indicated or only with extreme caution, since the preservation of the existing visual acuity must be regarded as having priority over the cosmetic findings. In cases of asymmetry or underdeveloped palpebral fissure, therapy can be started early in the first year of life without fear of resulting complications.

The Nasolacrimal Drainage System in 143 Children with the Microphthalmos-Anophthalmos Complex. / Tränenwegsbefunde von 143 Kindern mit Mikrophthalmus-Anophthalmus-Komplex.

BACKGROUND: Report of clinical findings relating to the lacrimal system in congenital clinical anophthalmos and severe blind microphthalmos (MAC-complex patients). METHODS: A retrospective study of the notes of 207 consecutive patients treated surgically at least once with highly hydrophilic self-inflating expanders for MAC between 1998 and 2021. The lacrimal drainage system was always probed and irrigated under general anaesthesia before any other procedure was started. RESULTS: 64 patients were excluded due to possible misdiagnosis because of previous lid or orbit surgery elsewhere or due to missing data. The analysis therefore included 67 girls and 76 boys aged between 1 and 126 months (median age: 5 months). 72 patients presented with unilateral and 42 with bilateral anophthalmos, and 24 had unilateral and 5 bilateral microphthalmos; consequently, 286 orbits (of which, 190 with probable pathology) were available for assessment. In unilateral cases the lacrimal system on the normal side was never affected. On the anophthalmic or microphthalmic side the lacrimal system was normal in 68 orbits only (35.8%). The most frequent finding was canalicular stenosis (91 orbits; 48%). Common canaliculus stenosis was observed in 12 orbits (6.3%) and nasolacrimal duct obstruction in 9 orbits (4.7%). There were four cases of punctal aplasia, but no other anomalies. In unilateral MAC pathologic findings during lacrimal probing were found to be associated with anatomical malformation of the contralateral fellow eye. Only in unilateral anophthalmos there was a significant association with cleft lip and palate, which was not found in the three other groups. CONCLUSIONS: In congenital clinical anophthalmos the lacrimal system is affected in up to 66.5% of cases, mostly due to canalicular stenosis. Even if there is no clear evidence of an embryological connection, this association is certainly not a random finding.

[Genetic analysis and prenatal diagnosis of a Chinese pedigree affected with microphthalmia/coloboma and skeletal dysplasia syndrome due to variant of MAB21L2 gene].

OBJECTIVE: To explore the genetic basis for a Chinese pedigree affected with microphthalmia. METHODS: Clinical data of the proband was collected. Whole exome sequencing (WES) was carried out to screen potential pathogenic variants in the proband. Candidate variant was verified by Sanger sequencing of the proband and his family members. Pathogenicity of the variant was predicted by searching the PubMed database and bioinformatic analysis. Sanger sequencing of amniotic fluid sample was carried out for prenatal diagnosis. RESULTS: The proband and his father were found to harbor a heterozygous c.151C>G (p.R51G) variant of the MAB21L2 gene. The same variant was not found in his mother and grandparents. Based on the guidelines of American College of Medical Genetics, the c.151C>G (p.R51G) variant was predicted as likely pathogenic. CONCLUSION: The c.151C>G (p.R51G) variant of the MAB21L2 gene probably underlay the microphthalmia in the proband. Above finding has facilitated prenatal diagnosis for this pedigree.

Comparisons of size of foveal avascular zone area among children with posterior microphthalmos, high hyperopia, and normal eyes.

PURPOSE: To determine the area of the surface foveal avascular zone (FAZ) in children with posterior microphthalmos (PM), high hyperopia, and normal eyes using optical coherence tomography (OCT) and OCT angiography (OCTA). METHODS: Thirty-six children were studied including 6 cases 12 eyes of PM (mean age 9.5 ± 5.2 years), 15 cases 30 eyes of high hyperopia (6.9 ± 1.5 years), and 15 cases 30 eyes of healthy individuals (8.7 ± 1.7 years). The B- and C-scan images in all children were recorded by OCT and OCTA with a scanning area of 3.0 × 3.0 mm centered on the fovea. All images were corrected for axial length differences, and the area of the FAZ surface and central macular thickness (CMT) was measured manually and compared. RESULTS: The area of FAZ in the PM group was 0.007 ± 0.003 mm2, which was significantly smaller than that in the high hyperopia eyes at 0.286 ± 0.108 mm2 and healthy eyes at 0.318 ± 0.129 mm2 (both P < 0.001). The CMT in the PM group was 401.58 ± 33.60 mm, which was significantly thicker than in the high hyperopia eyes at 202.93 ± 12.28 mm and the normal eyes at 204.43 ± 18.76 mm. The area of the FAZ and CMT in the hyperopia group did not differ significantly from that of the normal healthy eyes. CONCLUSION: These findings indicate that patients with PM have a hypoplastic macular region, which must be considered in any treatment of these eyes.

[Whole exome sequencing analysis and prenatal diagnosis for a Chinese pedigree affected with microphthalmia].

OBJECTIVE: To analyze clinical features and genetic cause for a Chinese pedigree affected with microphthalmia. METHODS: The proband and his parents were subjected to whole exome sequencing (WES) to identify potential pathogenic variants. Sanger sequencing was carried out to confirm the result of WES in available members from the pedigree. Prenatal diagnosis was provided to the proband's mother by genetic testing of amnionic DNA. RESULTS: A heterozygous nonsense mutation c.289C>T (p.R97*) was identified in the OTX2 gene among three patients from the pedigree by WES. The result was confirmed by Sanger sequencing. The proband's mother has carried the same mutation but did not have microphthalmia. The proband's father, aunt and the mother's fetus did not carry the mutation. CONCLUSION: The c.289C>T (p.R97*) mutation probably underlies the microphthalmia in this pedigree. Above result has facilitated genetic counseling and prenatal diagnosis.

[A Newborn Suffering from Arhinia: Neonatologic Challenges During Primary Care of the Newborn With Bosma Arhinia Microphthalmia Syndrome (BAMS)]. / Neugeborenes mit Nasenagenesie: Neonatologische Herausforderungen bei der Versorgung eines Neugeborenen mit Bosma-Arhinie-Mikrophthalmie-Syndrom (BAMS).

The rare clinical picture of nasal agenesis is to be presented on the basis of a female newborn. Intrauterine growth restriction with polyhydramnios and midface hypoplasia were noted during pregnancy. Primary cesarean section at 38 + 4 weeks' gestation was done. Airway management was achieved by splinting through a Mayo tube which was subsequently replaced by a pharyngeal endotracheal tube without signs of respiratory failure. In addition to a complete nasal agenesis, hypertelorism, a Gothic palate, bilateral microphthalmus, and iris coloboma were found. Ultrasound scans of cerebral structures were normal. An orogastric tube was placed, and drinking training and a special pacifier improved coordination and drinking performance. We suspected a case of Bosma arhinia microphthalmia syndrome (BAMS). The structural maintenance of chromosomes flexible hinge domain (SMCHD) containing 1 gene plays a key role in the embryogenesis of the human nose and is known for mutations in BAMS. A heterozygous de novo mutation in the SMCHD1 gene (c.1043A > G; pHis348Arg) was confirmed by molecular genetic analysis. Initial stabilization after birth is often a challenge in patients with nasal agenesis. They are often intubated immediately postpartum and electively tracheotomized. In the absence of respiratory problems and appropriate growth, however, there is no urgent indication for early plastic surgical treatment, given the inherent risks of sepsis and growth disorders in the midface.