Diagnosis, Early Care, and Treatment of Hallermann-Streiff Syndrome: A Review of the Literature.

Hallermann-Streiff syndrome is a rare congenital disorder characterized by a wide spectrum of craniofacial abnormalities. A review of the available literature reveals that only approximately 200 cases of the disease have been reported worldwide. For this article, we performed a literature review as a basis for a proposed scheme for early care and treatment. A comprehensive database search was carried out with the use of Medline (PubMed), ISI Web of Science, and ScienceDirect/Scopus. Of the 551 studies initially found, an evaluation using inclusion and exclusion criteria ultimately resulted in a total of 33 articles. Most of the articles are case reports, and only approximately 20% of these articles include treatment options. We propose an early care and treatment schedule based on the presented symptoms. [Pediatr Ann. 2021;50(5):e227-e231.].

Overarching control of autophagy and DNA damage response by CHD6 revealed by modeling a rare human pathology.

Members of the chromodomain-helicase-DNA binding (CHD) protein family are chromatin remodelers implicated in human pathologies, with CHD6 being one of its least studied members. We discovered a de novo CHD6 missense mutation in a patient clinically presenting the rare Hallermann-Streiff syndrome (HSS). We used genome editing to generate isogenic iPSC lines and model HSS in relevant cell types. By combining genomics with functional in vivo and in vitro assays, we show that CHD6 binds a cohort of autophagy and stress response genes across cell types. The HSS mutation affects CHD6 protein folding and impairs its ability to recruit co-remodelers in response to DNA damage or autophagy stimulation. This leads to accumulation of DNA damage burden and senescence-like phenotypes. We therefore uncovered a molecular mechanism explaining HSS onset via chromatin control of autophagic flux and genotoxic stress surveillance.

Hallermann-Streiff syndrome: A missing molecular link for a highly recognizable syndrome.

The use of modern next-generation sequencing-based approaches for gene identification has tremendously improved our understanding of the molecular pathogenesis of the great majority of well-known syndromes, whereas only a few remain to be elucidated. Hallermann-Streiff syndrome is such a disorder for which the molecular basis is still unknown although it represents a highly recognizable phenotype. Clinically, patients with Hallermann-Streiff syndrome show typical craniofacial dysmorphism, eye malformations, a distinctive facial appearance, abnormalities of hair and skin, short stature, and, interestingly, they might also present with aspects of premature aging. The clinical diagnosis is mainly given by the very typical facial gestalt of patients. In this review, we (a) summarize the current knowledge on the phenotypic traits, focusing on described classic cases, (b) discuss the missing molecular link, and (c) present innovative future strategies for gene identification.

Report on ocular biometry of microphthalmos, retinal dystrophy, flash electroretinography, ocular coherence tomography, genetic analysis and the surgical challenge of entropion correction in a rare case of Hallermann-Streiff-Francois syndrome.

PURPOSE: To report new aspects of the phenotype including Retinal dystrophy and surgical challenges in Hallermann-Streiff Francois syndrome (HSFS). METHODS: Detailed phenotype of a female with HSFS was evaluated including skeletal changes, comprehensive eye examination, detailed ocular biometry, electroretinography and macular Ocular coherence tomography. Surgical notes of lid surgery for entropion were reviewed. Genetic screening was also done. RESULTS: Unique Ocular biometry with electroretinography changes, macular folds and fundus changes suggestive of an unreported Retinal dystrophy in a typical patient with HSFS were noted. Surgery was challenging both due to difficulty in endotracheal intubation anaesthesia because of the dento-facial abnormalities and the skin fragility. CONCLUSION: This report provides additional information especially pigmentary retinal dystrophy, macular folds and electroretinography in HSFS. The microphthalmos had overlapping posterior segment findings usually reported with Nanophthalmos and Posterior microphthalmos. The surgical difficulties and outcomes of the rarely encountered adnexal abnormalities emphasize the need for a multi disciplinary approach for appropriate management.

Hallermann-Streiff syndrome with hemihypertrophy.

We report on a five year old girl with Hallermann-Streiff syndrome and hemihypertrophy. Hemihypertrophy does not appear to have ever been associated with Hallermann-Streiff syndrome.

Corneal opacities in the Hallermann-Streiff syndrome.

We present six patients with typical Hallermann-Streiff syndrome. All have microphthalmia and were operated for congenital cataract. Three of the patients developed a severe glaucoma and one patient presented repeated uveal effusions. Five of our patients have the same pattern of corneal stromal opacities. The opacities are ill defined and bilateral; the stroma between the opacities is clear. The opacities are observed in two children around the age of 5. Follow up of 10 years did not reveal a manifest increase of the lesions. The authors believe that corneal stromal opacities are a feature of the Hallermann-Streiff syndrome and they would urge ophthalmologists to look for this.

A homozygous GJA1 gene mutation causes a Hallermann-Streiff/ODDD spectrum phenotype.

Oculodentodigital dysplasia (ODDD) and Hallermann-Streiff syndrome (HSS) share several clinical characteristics. However, while ODDD is a dominantly inherited disorder due to mutations in the connexin 43 gene GJA1, the inheritance pattern of the HSS syndrome is still debated. Overlapping phenotypes have been described. In one of such cases we found a homozygous change at the very conserved R76 codon (c.227G>A, p.R76H), the clinically normal parents being heterozigous carriers of the same mutation. A different base change at the same codon (p.R76S) leads to a complete dominant ODDD phenotype. A case of full-blown HSS phenotype was also analysed but GJA1 mutations were not found. GJA1 homozygous hypomorphic mutations can result in a phenotype in the HSS/ODDD spectrum.

Hallermann-Streiff syndrome associated with small cerebellum, endocrinopathy and increased chromosomal breakage.

UNLABELLED: Hallermann-Streiff syndrome (HSS) is a rare clinic entity of unknown aetiology. Further clinical and metabolic-genetic evaluations are indicated. A 2-mo-old female baby presented with ocular abnormalities and severe failure to thrive since birth. The clinical features were compatible with the diagnosis of HSS. Further imaging, metabolic and cytogenetic examinations were performed. Features characteristic of HSS were dyscephaly with mandibular and nasal cartilage hypoplasia, microphthalmia, bilateral cataracts with congenital glaucoma, natal teeth and proportionate dwarfism. Rare anomalies such as choanal atresia and small cerebellum, very low insulin-like growth factor I level, hypothyroidism, generalized organic aciduria were also noticed. An increased chromosomal breakage rate is suggestive of the existence of some DNA repair defects in HSS patients. CONCLUSION: The associated anomalies in this patient may broaden the clinical spectrum of HSS. Underlying conditions of organic aciduria, growth factor deficiency and impaired DNA repair are likely to contribute to the progeria-like facies, congenital cataracts and growth failure.

Hallermann-Streiff syndrome: clinical and psychological findings in children. Nosologic overlap with oculodentodigital dysplasia?

We describe 3 young children with Hallermann-Streiff syndrome, 2 with typical manifestations and 1 with the facial changes without the eye abnormalities but with a cleft palate and with complete syndactyly of fingers IV and V. The latter case represents overlap of the Hallermann-Streiff syndrome and oculodentodigital dysplasia. "Dwarfism" as a possible clinical risk marker of mental retardation is discussed. As cause, a mendelian autosomal dominant mutation seems most probable.

Congenital cataracts in mother, sister, and son of a patient with Hallermann-Streiff syndrome: coincidence or clue?

The son of a patient with Hallermann-Streiff Syndrome (HSS) was found to have congenital cataracts, but no other findings of the syndrome. Similar findings were reported in the patient's mother and sister. The significance of this observation is uncertain.

[Spontaneous bilateral lens resorption in a case of Hallermann-Streiff syndrome]. / Spontane beidseitige Linsenresorption bei einem Fall von Hallermann-Streiff-Syndrom.

The Hallermann-Streiff-syndrome was first described in 1948 by Hallermann and in 1950 by Streiff. The most common features are dyscephalia, cataract, microphthalmia, dental anomalies, hypotrichosis, cutaneous atrophy, and nanism. Anomalies of the eye include cataract, microphthalmia, nystagm, strabism, blue sclera, fundus anomalies and combined anomalies of all segments of the eye. The frequency of cataract is about 90%. Spontaneous resorption of the lens is described in about 8%. We present a five year old girl showing the typical dyscephalia of the Hallermann-Streiff-syndrome (bird face). Her lenses were replaced by opaque membranes. These membranes presumably were remnants of the posterior lens capsule.

Successful pregnancy in a patient with Hallermann-Streiff syndrome.

Reproductive capacity has not been studied in patients with Hallermann-Streiff syndrome, but successful pregnancy in these patients is rare. A patient with the classic signs--plus a müllerian developmental anomaly, hypertension, glaucoma, and an extensive surgical history--was artificially inseminated, and a term gestation ensued.

[The Hallermann-Streiff syndrome in 2 generations]. / Hallermann-Streiffov syndróm vo dvoch generáciach.

The authors discuss a rare case, unique in our literature, of the familial incidence of Hallermann-Streiff's syndrome and the treatment of some of its complications. Special emphasis is laid on genetic analysis which provides evidence of autosomal dominant heredity with a variable expressivity of the pathological gene, and which must be applied in genetic consultations.