Massachusetts' Findings from Statewide Newborn Screening for Spinal Muscular Atrophy.

Massachusetts began newborn screening (NBS) for Spinal Muscular Atrophy (SMA) following the availability of new treatment options. The New England Newborn Screening Program developed, validated, and implemented a screening algorithm for the detection of SMA-affected infants who show absent Exon 7 by Real-Time™ quantitative PCR (qPCR). We screened 179,467 neonates and identified 9 SMA-affected infants, all of whom were referred to a specialist by day of life 6 (average and median 4 days of life).

Ten Years of Newborn Screening for Severe Combined Immunodeficiency (SCID) in Massachusetts.

Background: Massachusetts began newborn screening (NBS) for severe combined immunodeficiency (SCID) using measurement of T-cell receptor excision circles (TRECs) from dried blood spots.

Objective: We describe developments and outcomes from the first 10 years of this program (February 1, 2009, to January 31, 2019).

Methods: TREC values, diagnostic, and outcome data from all patients screened for SCID were evaluated.

Noonan syndrome with loose anagen hair associated with trichorrhexis nodosa and trichoptilosis.

We report a case of Noonan syndrome with loose anagen hair (NS/LAH), a rare variant of Noonan syndrome, with associated trichorrhexis nodosa and trichoptilosis. The mutation may be responsible for these additional hair shaft defects, revealing the importance of microscopic examination of hairs in these patients.

WRN Mutation Update: Mutation Spectrum, Patient Registries, and Translational Prospects.

Werner syndrome (WS) is a rare autosomal recessive disorder characterized by a constellation of adult onset phenotypes consistent with an acceleration of intrinsic biological aging. It is caused by pathogenic variants in the WRN gene, which encodes a multifunctional nuclear protein with exonuclease and helicase activities. WRN protein is thought to be involved in optimization of various aspects of DNA metabolism, including DNA repair, recombination, replication, and transcription.

Multiple Café au Lait Spots in a Group of Fair-Skinned Children without Signs or Symptoms of Neurofibromatosis Type 1.

Background: The presence of six or more café au lait (CAL) spots is a criterion for the diagnosis of neurofibromatosis type 1 (NF-1). Children with multiple CAL spots are often referred to dermatologists for NF-1 screening. The objective of this case series is to characterize a subset of fair-complected children with red or blond hair and multiple feathery CAL spots who did not meet the criteria for NF-1 at the time of their last evaluation.

The phenotypic spectrum of Schaaf-Yang syndrome: 18 new affected individuals from 14 families.

Purpose: Truncating mutations in the maternally imprinted, paternally expressed gene MAGEL2, which is located in the Prader-Willi critical region 15q11-13, have recently been reported to cause Schaaf-Yang syndrome, a Prader-Willi-like disease that manifests as developmental delay/intellectual disability, hypotonia, feeding difficulties, and autism spectrum disorder. The causality of the reported variants in the context of the patients' phenotypes was questioned, as MAGEL2 whole-gene deletions seem to cause little or no clinical phenotype.

Methods: Here we report a total of 18 newly identified individuals with Schaaf-Yang syndrome from 14 families, including 1 family with 3 individuals found to be affected with a truncating variant of MAGEL2, 11 individuals who are clinically affected but were not tested molecularly, and a presymptomatic fetal sibling carrying the pathogenic MAGEL2 variant.

De novo mutations in PURA are associated with hypotonia and developmental delay.

PURA is the leading candidate gene responsible for the developmental phenotype in the 5q31.3 microdeletion syndrome. De novo mutations in PURA were recently reported in 15 individuals with developmental features similar to the 5q31.

Newborn screening for severe combined immunodeficiency in 11 screening programs in the United States.

Importance: Newborn screening for severe combined immunodeficiency (SCID) using assays to detect T-cell receptor excision circles (TRECs) began in Wisconsin in 2008, and SCID was added to the national recommended uniform panel for newborn screened disorders in 2010. Currently 23 states, the District of Columbia, and the Navajo Nation conduct population-wide newborn screening for SCID. The incidence of SCID is estimated at 1 in 100,000 births.

Dystrophic epidermolysis bullosa associated with amniotic band syndrome.

Amniotic band syndrome (ABS) is a term used to describe congenital anomalies that result from the entrapment of a fetus in fibrous bands. We describe two male infants born with features of dystrophic epidermolysis bullosa (DEB) and ABS. These cases add to the few previous reports of simultaneous DEB and ABS.

BCOR analysis in patients with OFCD and Lenz microphthalmia syndromes, mental retardation with ocular anomalies, and cardiac laterality defects.

Oculofaciocardiodental (OFCD) and Lenz microphthalmia syndromes form part of a spectrum of X-linked microphthalmia disorders characterized by ocular, dental, cardiac and skeletal anomalies and mental retardation. The two syndromes are allelic, caused by mutations in the BCL-6 corepressor gene (BCOR). To extend the series of phenotypes associated with pathogenic mutations in BCOR, we sequenced the BCOR gene in patients with (1) OFCD syndrome, (2) putative X-linked ('Lenz') microphthalmia syndrome, (3) isolated ocular defects and (4) laterality phenotypes.

Deletion 22q11: spectrum of associated disorders.

Velocardiofacial syndrome, also called Shprintzen syndrome or DiGeorge sequence, is one of the most common genetic disorders in humans. Caused by a microdeletion on chromosome 22, it manifests in a remarkable variety of symptoms in multiple systems. The most frequent anomalies involve palatal function, facial features and congenital cardiac defects.

Gene therapy improves immune function in preadolescents with X-linked severe combined immunodeficiency.

Retroviral gene therapy can restore immunity to infants with X-linked severe combined immunodeficiency (XSCID) caused by mutations in the IL2RG gene encoding the common gamma chain (gammac) of receptors for interleukins 2 (IL-2), -4, -7, -9, -15, and -21. We investigated the safety and efficacy of gene therapy as salvage treatment for older XSCID children with inadequate immune reconstitution despite prior bone marrow transplant from a parent. Subjects received retrovirus-transduced autologous peripherally mobilized CD34(+) hematopoietic cells.

Townes-Brocks syndrome: twenty novel SALL1 mutations in sporadic and familial cases and refinement of the SALL1 hot spot region.

Townes-Brocks syndrome (TBS) is an autosomal dominant malformation syndrome characterized by renal, anal, ear, and thumb anomalies caused by SALL1 mutations. To date, 36 SALL1 mutations have been described in TBS patients. All but three of those, namely p.

Mosaic tetraploidy and transient GFI1 mutation in a patient with severe chronic neutropenia.

This report presents the case of a 15-year-old male with severe chronic neutropenia, leukopenia, and persistent tetraploid mosaicism in the bone marrow and peripheral blood. His father had mild neutropenia and bone marrow tetraploidy. Flow cytometric analysis of DNA content peripheral blood showed tetraploidy in 20% of granulocytes and 15% of monocytes.

Familial immunodeficiency with cutaneous vasculitis, myoclonus, and cognitive impairment.

We report a family with five of six siblings (including identical male twins) with a novel constellation of immunologic and neurologic impairments. Affected subjects experienced severe dermatitis starting around 9 months of age, Stevens-Johnson syndrome in early childhood, and extreme elevations of IgE (9,400-43,000 IU/ml). The oldest sibling died at age 27 of respiratory failure following recurrent, severe pneumonias.